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Human Life Sciences Research Aboard theInternational Space Station and the SpaceShuttle: A White Paper

-- LH Kuznetz 06/18/03

CONFIDENTIAL… NOT FOR DISTRIBUTION

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Acknowledgment

This manuscript was compiled from the input of many people in the Space and Life Sciences Divisionand represents 21 months of effort. Special thanks go to Al Feiveson, who provided statistical guidancefor the Analytical Heirarchy Pairwise method and created the Excel program for the Moving TargetApproach. Others whose data formed the foundation of this work include the Experiment ScienceManagers (ESMs); Internal and External Principal Investigators; Increment Scientists; DSO FlightExperiment Managers and Medical Operations Personnel. Without the input of these passionate anddedicated people, the key conclusions reached in this white paper would not have been possible.

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Extraordinary Claims Require Extraordinary Evidence

……Sagan

Extraordinary Problems Require Extraordinary Actions

….Kuznetz

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Introduction

By dictate of the Young Commission Report investigating the utilization of the International Space Station (ref 1),biomedical research in general, and the development of countermeasures to prevent the deleterious effects ofexposure to microgravity on astronauts in particular, are the top priorities of the program. This research, under theauspices of NASA’s Biomedical Research and Countermeasure Program of the Office of Bioastronautics consists ofa ground analog program and flight program. The purpose of this study is to:

1. Describe how the current flight program works

2. Summarize the status of the current flight program

3. Recommend improvements to enhance the effectiveness and efficiency of the current program

While no attempt was made to analyze the ground analog program or any other program at NASA, many of therecommendations of this study may be applicable as well.

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1. THE CURRENT FLIGHT PROGRAM

The Strategic Plan for NASA's Human Exploration and Development of Space (HEDS) Enterprise outlinesa number of goals and objectives, one of which is to:

"Develop biomedical knowledge and technologies to maintain human heal th andperformance in space".

To fulfill this objective, the Office of Bioastronautics instituted the Biomedical Research and CountermeasuresProgram to provide for the flight of relevant biomedical experiments. These experiments fall into the following 3categories:

• HRF (Human Research Facility)—experiments that fly on ISS in the HRF rack.

The HRF (Human Research Facility) is a complement of hardware and payload experiments on the InternationalSpace Station (ISS) designed to chronicle and develop countermeasures to the effects of long-duration space flight.It consists of an all-drawer International Standard Payload Rack(s) that provides services and utilities includingelectrical power, command and data handling, cooling air,water, pressurized gases, and vacuum. The rackaccommodates drawer mounted experiments and instruments using the International Subrack Interface Standard(ISIS) for structural, power, and data interfaces.

• DSOs (Detailed Supplementary Objectives)—experiments that fly on STS.

DSOs or Detailed Supplementary Objectives are experiments designed to fly on the Space Shuttle orSpace Transportation System (STS) that chronicle and develop countermeasures to the effects of short-duration space flight. They differ from ISS experiments by their duration. Generally speaking,physiological response time provides the key distinction between ISS and STS experiments. Physiologicalsystems whose response peaks in less than a month (Figure 1) are designated to the DSO program whilethose with longer time constants are usually (but not always) assigned to ISS. DSOs can be as complex asa set of instruments manifested and installed on a Space Shuttle flight(s) or as simple as a logbook entrynoting crew response to a particular parameter, such as light, sleep or behavioral interactions.

Figure 1

Figure 1

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• SMOs (Supplementary Medical Objectives) )—experiments that fly on ISS with expedited approvaland rapid turnaround.

SMOs or Supplementary Medical Objectives promote basic research concerned with fundamental ormechanistic questions about the role of gravity in life processes. Designed to fly on ISS with expeditedapproval and rapid turnaround, SMOs are experiments strongly anchored in previous ground-basedresearch. They utilize a sequential decision-making process that depends on a method of repeatedconfidence levels. Unlike HRF experiments or DSOs, the number of crew members required for statisticalsignificance is not predetermined but revised with each new mission and crew complement (Ref 2-CEVPWork Project Plan for additional details).

The above life science experiments may be further subdivided according to how their data is collected, ie., in-flight

only; pre/post flight only and both in-flight and pre/post flight. They cover a wide range of disciplines cover a wide range of disciplinesincluding:

• Bone• Cardiopulmonary• Neurovestibular• Pharmacology• Human behavior and performance• Immunology, infection and Hematology• Muscle• Toxic Exposure• Multisystem (cross-risk) alterations• Nutrition, fitness and rehab• Clinical Operational Medicine• Radiation

The Bioastronautics program currently manages 45 experiments. Of these, 15 are DSOs, 25 are ISS experiments, 3are joint DSO/ISS experiments and 3 are international investigations under the direction of the BR&C program.Another 10-15 are Russian experiments or ESA experiments not managed or funded by NASA. The BR&Cmanaged experiments are shown in Figure 2, grouped by discipline.

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Figure 2. ISS/Shuttle Research Program by Critical Risk, Discipline, Mechanism and Priority

Discipline PI Title M/CM Risk# Rank (Bal) Crit Q# Duration (L/S)

CardioCohen Stability M 13,14 Red1,Ye2 3.01,05, 08, 09 L/SMeck Ortho Intol M 14 Yellow 2 3.05, 3.06 SMeck (SMO) Midodrine CM 14 Yellow 2 3.09 LBungo/Lev Cardio M 13,14,15 Red1,Ye2,Gr 3.01, 06,3.18 LHughson Card Control M 14, 15 Ye 2, Gr 3.05, 3.17 L(CSA)Gabrielson Xenon M 14 Yellow 2 3.05 L (ESA)

Neuro

Bloomberg Mobility CM 34 Yellow 2 9.04, 9.22, 9.24 LClement Ovar M 33 Red 1 9.05, 9.25 SMerfeld Sens Int M 33, 34 Red 1, Ye2 9.02, 9.03, 9.09 L/SMoore Spin CM 33, 36, 14 Red 1, Ye2 9.01, 9.15/16, 3.09 SPaloski Spacial M 33, 34 Red 1, Ye2 9.01, 9.23, 9.25 SWatt H-Reflex M 34 Yellow 2 9.22 L

BoneLang Subr. Bone M 10 Yellow 2 2.01, 2.14 LCavanaugh Foot M 9, 10 Red 2, Ye2 2.02, 2.25, 2.26 LSmith Ca Kinetics M 9 Red 2 2.25 STS-107Whitson Renal ISS CM 12 Yellow 2 2.06 LWhitson Renal (STS) CM 12 Yellow 2 2.06 S+ STS107Tesch Fracture M 10 Yellow 2 2.07 status ??Rubin Vibe CM 9, 10, 28 Red 2, Ye2 2.14/19/26, 8.01 LLeBlanc Alendronate CM 9, 10 Red2, Ye2 2.19, 2.08, 2.06 L

Muscle

Fitts Biopsy M 31 Yellow 1 8.07 LDe Luca q Muscle M 28, 32 Yellow 1 8.06, 8.08 SFerrando Protein turn M 30 Yellow 1 8.04 STS 107Stein Glucose kine. M 30 Yellow 1 8.05 status ???

Pharmaco

Putcha PMZ M 45 Yellow 1 11.17/18/19 SPutcha GI alter. M 45 Yellow 1 11.16 SBrunner Pharmaco M 45 Yellow 1 11.16, 11.19 L

Immune

Pierson Viral Shed. M 22 Yellow 2 7.04 SPierson Imm. Def ch. M 22 Yellow 2 7.03 STS107Pierson Swab* M 22, 8 Yellow 2 7.11/13; 5.12 LStowe Ep Barr React M 22 Yellow 2 7.23 SUchakin Cytokine Bal M 22 Yellow 2 7.03, 7.28

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Figure 2 (cont’d)

Discipline PI Title M/CM Risk Rank(Bal.) Crit Q# Duration

Behavior and Performance

Kanas Interactions M 18 Red 1 6.01, 6.03 LKanas Psycosocial M 18 Red 1 6.01, 6.03 LStuster Journals M 18 Red 1 6.01, 6.03 LOman** Voila M 20 Green 1 6.12 LCzeisler Sleep/Wake M 19 Red 2 6.06, 6.08 L

Food and Nutrition

Pierson Swab* M 8, 22 Yellow 1 5.12; 7.11/13 L

Radiation

Thompson EVARM M 38 Red 1 10.06, 10.09 L/SObe Chromosome M 38 Red 1 10.05, 10.09 LBadwhar Phantom M 38 Red 1 10.09, 10.11 L

Toxic Exposure

West Puff M 44 Yellow 2 11.13 L

Multisystem

Good Intra. Press M 49 Yellow 2 12.01 S Schneider Treadmill CM 49, 10 Yellow 1, 2 12.01, 2.07 L

17, 29,30 3.13, 8.04, 8.08

Clinical/Operational

Dulchavsky Ultrasound M 43 Red 1 11.03 L

*Doubled up as Immune and Food/Nutrition Disciplines, CR# 22 and 8**Possible double up as Behavior/Performance and Neurovestibular, CR# 20 and 33

Prepared by LH Kuznetz, 4/22/03

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Experiment Acquisition

Flight experiments are acquired, selected, developed, manifested and flown in accordance with the process shown inFigure 3 below.

Headquart

ers

NRA Solicitation

Proposals Submitted

Peer Review

Experiment Selection

Experiment assigned to

JSC

Successful Proposals

NRA Technical

Inputs

Engineering Cost & Management (ECM) Review

Supplementary studies as required

Payload-Level Reviews (program unique)

FLIGHT

Data transfer to

PIs

JSC/FEDP

JJSSCC//FFEEDDPP

Contract phases incremented as

required

Experiment-Level Reviews: ERRs, PDRs, CDRs, etc.

(program unique)

PI Contract established

Paylo

ad

Org

aniz

ati

ons

Figure 3. Experiment Acquisition and Processing

As depicted above, the program acquires new experiments through the preparation of solicitations such as NASAResearch Announcements (NRAs). Proposals can originate from a variety of sources such as a NASA NRA, NSBRINRA, NAR (non-advocate review or SMO) or an unsolicited proposal. Each proposal is subjected to a process ofpeer review then to an implementation feasibility assessment (the Engineering, Cost, and Management or ECMreview). Once selected, Code U at NASA Headquarters assigns management responsibility to the Office ofBioastronautics at JSC, in the person of the Human Adapatation and Countermeasures Office (HACO) Chief and theBR&C Flight Projects Manager. The Flight Projects Manager, in turn assigns responsibility for development,integration and implementation to the Mission and Planning Management Office (MPMO).

The experiment development process is shown more fully in Figure 4, which portrays the sequence of events asexperiments move through the process. Precise timing of the phases vary from experiment to experiment and can beeffected by flight platform, complexity, schedule delays, paradigm shifts, budget constraints and other factors.Experiment requirements are ultimately defined in an ED (Experiment Document) common to all platforms. In thecase of DSOs, more details are available in the FTSOD (Flight Test and Supplementary Objectives Document),which provides information required by the Mission Operations Division (MOD) for flight implementation. TheFTSOD contains information pertinent to all aspects of mission operation such as in-flight crew time, schedulingand constraints, stowage and power requirements, hardware, certification milestones, KSC interfaces, etc.

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NASA Res

earc

h Ann

ounc

emen

t

Exper

imen

t Req

uirem

ents

Review

Prelim

inary

Des

ign R

eview

Critica

l Des

ign R

eview

Experiment

Completed

Selection Definition Design Development Execution Data Distribution

• Solicitation

• Evaluation

• Selection

• Statement ofWork

• T-Order Award

• ExperimentDocument

• IRB protocol

• Developmentschedule

• Cost-to-complete

• Experiment ContractAward

• Hardware/softwaredesign

• Crew proceduredevelopment

• IRB submittal/review

• Safety Reviews

• Flight assignment

• Training andsimulations

• Hardware/softwaredevelopment

• Certification/accept-ance testing

• Science verificationtesting

• Experimentintegration planning

• Phase III SafetyReview

• Preflight baselinedata collection

• Inflight operations

• Postflight baselinedata collection

• Data analysis andreport

• Data archival

• Final report

Figure 4. Flight experiment flow process (idealized)

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Manifesting

Figure 5 illustrates the process by which experiments are assigned to specific flights.In brief, as each STS mission or ISS increment opportunity arises, the JSC elements that “own” potential flightcandidates meet as the Flight Projects Clearinghouse in order to review:

1) available flight resources associated with the flight,

2) element flight activities that are or will be ready to fly in time to take advantage of the flight opportunity,

3) flight resource requirements necessary to perform the activities, and

4) program element priority

Figure 5. Manifesting Process

SD provides Medopsreq’ts for mission.

SA Divisions identifyresearchinvestigations formission.

All req’tsareintegratedinto afeasiblecomplement or optionsare

devised.

PreClearinghouse

Missioncomplementor optionsare presented.Clearinghouse concurs oncomplement.

Clearinghouse

Clearinghousecomplementpresented.Final approvalforimplementation is granted.

FACB

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The Clearinghouse produces an agreed-upon set of flight activities that can be accommodated by the available flightresources and that represent an appropriate distribution of those resources between the program elements. Theseactivities ensure that the proposed flight activities are relevant to the overall scientific goals of the BioastronauticsProgram. Subsequent to the Clearinghouse, the flight activities package is subjected to a more rigorous technicalreview by a team of representatives selected from each program element. This review of the package examines indetail the flight resources required to assure that the necessary vehicle/crew resources are available on the projectedflight(s) and to further verify that the elements are operationally compatible but not duplicative.Following completion of this second review, the final package is presented to the Bioastronautics Flight ActivitiesControl Board (FACB) for the final manifest decision. The review process and boards to which each experiment issubjected includes may not be limited to the following: :

• MPMO internal reviews (Pre-Clearinghouse, SM- CCB, other)

• BR&C Prioritization Review

• HACO CCB

• Clearinghouse

• FACB

• Crew Briefing Review

• FPSR (Flight Planning and Stowage Review)

• SORR (Stage Operation Readiness Review)

• CoFR

• FRR

Management

Programmatic review and manifest approval of Bioastronautics-managed experiments is a multi-step process. Theinitial selection for definition approval resides with Headquarters Office of Biological and Physical SciencesResearch (OBPR; Code UB), which utilizes Bioastronautics Program recommendations. At the completion of theexperiment definition phase, JSC prepares a recommendation as to whether experiments either be selected forfollow-on development/flight or be deselected from the program. These “decision packages” are prepared by JSCand forwarded to Headquarters for final decision. If selected and assigned to flight, an experiment enters thepreparation phase, initiating the process of crew training. From this point hence, changes to its implementation,including details of training, scheduling, baseline data collection, Pre/In/Post-flight data collection and so on canonly be approved by the Project Scientist or Increment Scientist assigned to the flight, and the BR&C FlightProjects Manager. Such changes do not require approval or concurrence by the Bioastronautics Program Manager orthe FACB as long as the experiments’ goals, objectives, and science content have not been compromised. However,the Bioastronautics Program Manager and the FACB must be appraised of significant adjustments in order to assessadditional flight opportunities that might be required to fulfill the scientific objectives of the experiment.Experiments may also be removed from the program for several reasons. Lack of developmental progress, changesin budgetary and flight resources, and changes in program priority can result in the removal of experiments fromspecific flights (demanifesting) or from the flight program entirely (deselection). The specific removal process andthe authority to authorize removal depend upon the rationale for removal. The process of removing experimentscan be initiated by recommendations from the JSC experiment teams (experiment-driven criteria), theBioastronautics Chief Scientist (programmatic considerations), or by the Project or Increment Scientist assigned tothe mission (flight resource/flight design changes). Regardless of the source, the deselect recommendation must bereviewed and approved by the Bioastronautics Chief Scientist. The Chief Scientist will assure that all other avenuesof keeping the experiment in the program have been considered before recommending deselection. An experimentrecommended for deselection must be approved by NASA Headquarters Code UB, while recommendations fordemanifesting require concurrence only from the JSC FACB. In the latter case, alternate flight assignments will beassessed and approved through the cycle described above and in Figure 4.

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Critical Path Roadmap

The primary goal Bioastronautics Program is to protect and improve the health, safety, and productivity of flightcrews during short duration Shuttle flights and longer duration flights on the International Space Station (ISS).These goals will provide the necessary underpinnings for astronaut safety and health care in future exploration classspaceflight programs. Improvements in ground-based health care and health-care systems are also an importantobjective of the program. The Program centerpiece is a tightly integrated and focused strategy emphasizing riskreduction, mitigation, and management. Both ground-based and flight-based research and technology componentsare used in this integrated approach. The approach encompasses the following elements: 1.) astronaut health care,both on the ground and inflight, 2.) applied biomedical research into elucidating the physiological adaptations to themicrogravity environment, 3.) development of physiological/psychological systems countermeasures to ameliorateand/or counteract the effects of exposure to microgravity, 4.) research and technology in biotechnology and cellsciences, and 5.) research and technology in the development and application of advanced life support systems forlong-duration spaceflight.Each element of the program is based upon requirements sets that have been rigorously developed utilizing bothintramural and extramural medical and scientific guidance. These requirements provide solid scientific “roadmaps”and guidelines for the research and technology projects outlined in this plan.The CPR is designed to facilitate the resolution of biomedical problems in long-duration space flight by identifyingrelevant risks and then suggesting pathways for solutions to those risks. As a process, it guides efforts to identify,assess, track, manage and document the resolution of biomedical risks, associated risk factors, as well as the criticalscientific questions to be addressed to increase safety, health and performance of crews during and after extendedspace flight missions. As a tool, it allows informed decision-making for allocation of limited resources to supportfocused research and technology efforts and selection and implementation of optimal risk reduction strategies.

The BCPR has been a joint project of NASA the JSC Bioastronautics Program and the NSBRI since 1998. Workingtogether in an analysis based on long duration human exploration missions (specifically, the Mars Design ReferenceMission, 1997), jointly-led discipline teams identified 55 risks comprising 251 unique critical questions (CQ) across12 discipline areas in 3 major categories:

• Habitation Systems: 11 risks, 74 CQ*• Human Adaptation and Countermeasures Systems: 38 risks, 190 CQ*• Medical Care Systems: 6 risks, 39 CQ*(* Note that certain CQs may be applicable to more than one category or risk.)

Overlapping subsets of these risks apply to all categories of piloted space flights, including missions aboard theSpace Shuttle, the International Space Station (ISS) and future exploration missions to destinations other than Mars(e.g., the Moon, or the Earth-Moon L1 and Sun-Earth L2 points).

The BCPR process provides a set of products that are useful in programmatic oversight.An annual report rates NASA’s funded research and technology activities in human space life sciences in relation tothe CPR, with recommended changes in program content or direction. All proposed NASA biomedical tasks arereviewed for their “congruence” with the CPR (including risks, CQs, CRL, rankings, and deliverables). The BCPRsupports development and implementation of strategies and allocation of resources for optimal risk reduction basedon recommendations of BCPR experts. Additionally, BCPR content and process is available to the global researchcommunity through appropriate avenues (web site, scientific meetings, publications, etc.).

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Early in the development of the BCPR, the 55 risks were compared and rated, in terms of relative importance andmaturity of countermeasure concepts, across all discipline areas by a panel of NASA and NSBRI experts. Four“types” of risk were identified, based on specific criteria:

Type I (4 risks, 7%)• Potentially most significant impacts on mission or crew, AND• Demonstrated or strongly suspected risks, AND• NO countermeasures currently effective in reducing these to acceptable level;

Type II (28 risks, 51%)• Potentially significant impacts on mission or crew, AND/OR• Additional research required to demonstrate risks, AND/OR• NO ground validation of countermeasure effectiveness;

Type III (23 risks, 42%)• Potentially serious impacts on mission or crew, AND/OR• Additional research required to evaluate risks, AND/OR• Effective countermeasures in existence but not in use (e.g., NO space verification of thecountermeasure).

Type IV• Problems have been identified and risks have either been mitigated or require no further mitigation

The goal of the BCPR is the reduction, if not outright elimination, of the risks to humans inherent in long-durationspace flight. In this process, the metric of most value is a demonstrable risk reduction to acceptable levels achievedthrough the development of deliverables, including:

• Risk assessment and acceptance wherever necessary• Scientific knowledge of mechanisms and processes (including model-derived data)• Development of requirements to mitigate risks (e.g., nutrition, exercise, pharmacological strategies

etc.)• Development of medical interventions (diagnosis, treatment, and rehabilitation capabilities) as

appropriate• Crew screening and selection criteria• Crew training techniques and content• Design specifications for spacecraft and subsystems (e.g., artificial gravity)• Mission operations to avoid risks whenever possible

Deliverables that include countermeasures (whether hardware or procedures) can be assigned a CountermeasureReadiness Level (CRL) which identifies the maturity of a countermeasure (CM) or technology deliverable. The nineCRL levels (e.g., stages of CM maturity) are:

1. Phenomenon observed and reported; problem or risk defined.2. Hypothesis formed; preliminary studies to define parameters and feasibility.3. Hypothesis validation and understanding of scientific processes or mechanisms.4. Formulation of CM concept based on scientific understanding of phenomenon.5. Proof of concept testing and initial demonstration of CM feasibility and efficacy.6. Laboratory/clinical testing of CM in subjects to demonstrate efficacy.7. Evaluation of CM in human subjects in controlled laboratory simulating space flight.8. Validation with human subjects in actual space flight to demonstrate efficacy and operational feasibility.9. CM fully flight tested and ready for implementation.

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To facilitate discussion and comparisons of funded tasks, these stages may be grouped according to whether theyencompass basic research (CRL 1-3), feasibility testing (CRL 3-5), CM development for the operationalenvironment (CRL 4-7), CM demonstration in the operational environment (CRL 7-8), or operationalimplementation (CRL 9). These levels are incorporated into the “pyramid” shown in Figure 6.

Figure 6. The Ground to Flight Countermeasure Pyramid

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2. STATE OF THE CURRENT PROGRAM

Despite the apparent order of the process described above, the reality of the current program tells a more chaoticstory. Metrics for the program appear in Figure 7, which reveal that of the 45 experiments either in or about to enterthe flight queue, only 13 are designated Red 1 or highest priority, compared to 27 that are Yellow or lower priority.More disturbing is the fact that 18 of these 27 areYellow 2, the next to lowest tier of importance. (The Red, Yellow,Green designation was established by the REMAP commission for a balanced program (Appendix 1). Ignoring forthe moment what this says about the science value, only 6 of the 45 are countermeasures (15%) while 85%constitute mechanistic or fundamental studies with no clear path to a countermeasure. This is a clear contradiction tothe dictate established by the Young Commission that the development of countermeasures to prevent thedeleterious effects of microgravity is the primary mission of ISS.

Another foreboding statistic relates to the number of studies that have overlapping objectives (as noted by theCritical Path Risks and Questions) and measure similar parameters yet are manifested and treated as if they wereunrelated. This lack of commonality stretches out the queue far beyond what it need be, accumulating costs andwaste in return. This is especially true for the Cardiovascular and Neurovestibular Disciplines, with 12 experimentsbetween them. To put it in perspective, they would take 8 years to complete at an average duration of 4 years perexperiment if 6 could be run in parallel and manifested at the same time, as opposed to 48 years if they were run inseries. While the latter is a play on extremes, it gets the point across that not combining resources for relatedexperiments is terribly wasteful. Throw in the fact that 6 of the 12 experiments in cardio and neuro are Yellow 2’sthat clog the queue with second tier objectives and block new Category Reds from entering, and the stated BR&Cgoal of obtaining and implementing a countermeasure after 3 category Red experiments per discipline is pie in thesky.

Another concern is the quality of the science itself. Few if any of the experiments have valid controls in the usualsense of the word. They appear to, using pre and post flight data on the same individual, but subject-to-subjectvariations; restrictions imposed by Medical Operations; data sharing and other constraints (addressed below)conspire to confound results. Unfortunately, there is a “we have to live with it, that’s the nature of the beast,”mentality that has become the mantra, and controlled or cross disciplinary studies aimed at devariable-izing the mixare few and far between. Together with the small N size typical of most flight experiments, the line between real andwishful science is continually being blurred.

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Figure 7. FLIGHT PROGRAM SUMMARY AS OF 6/03*

Human Life Science Flight Experiments• 6 Cardio (2 red, 4 yellow) + 2 proposed (Rhythms, ESA, D’Anno, SMO)• 6 Neuro (4 red, 2 yellow)• 7 Bone (4 red, 3 yellow)**• 4 Muscle (4 yellow)• 3 Pharmaco (3 yellow)• 5 Immune (5 yellow)• 5 Behavior (4 red, 1 green)• 1 Food and Nutrition (1 yellow)• 3 Radiation (3 red)• 1 Toxic (1 yellow)• 2 Multisystem (2 yellow)• 1 Clinical/Operational (1 red)• TOTAL = 45

Platforms• ISS only (long duration) = 25• DSO only (short duration) = 12• Joint experiments (ISS and DSOs) = 3• STS-107 experiments = 4 (future status unknown)• Status uncertain/unknown = 2 (Tesch, Stein)

Priority Ranking (balanced program)• Red = 18 (13 Red 1, 5 Red 2)• Yellow = 27 (9 Yellow 1, 18 Yellow 2)• Green = 1

Mechanisms/Countermeasure metrics• Mechanistic studies = 38 (85 %)• Countermeasure studies = 7 (15 %)*

Countermeasure Studies• 1 in Cardio (Midodrine)• 2 in Neuro ( Mobility, Spin)• 3 in Bone (Renal, Vibe, Alendronate)• 1 in Multisystem (Treadmill)• 0 in Muscle, Pharmaco, Immune, Behavior/Performance, Radiation, Food/Nutrition, Toxic Exposure,

Clinical/Operational

Notes:* includes actual & planned experiments & SMOs, counts top risk tier only, does not include Russian expts** Renal is a separate study on ISS and STS platforms but counts as a single countermeasure

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NRAs.

The problems above start and end with the solicitation process. The flight NRAs seek research proposals that will“lead to the development of effective countermeasures or operational techniques for problems associated with one ofthe 12 disciplines covered by the Critical Path Roadmap.” However, of the 21 proposals that made the final cut inthe 2001 solicitation, only 1 was a bona-fide countermeasure (Rubin) and it, in all likelihood, will be downgraded toa ground study prior to flying because it “lacks sufficient ground data pedigree in humans.” The pattern is notrestricted to Flight NRAs. The 2002 Ground NRA solicitation drew over 100 proposals and only 5 countermeasures(2 of which were non funded international studies). Such a track record is discouraging, especially in light of the factthat the current flight program is already bloated with 84 % mechanistic studies. The problem doesn’t end here,however, the underpinnings of the entire NRA process are questionable. Specifically:

• The process seeks to be all inclusive with NASA’s international partners, but our largest partner, theRussians, are excluded and have their own separate process

• The peer review process uses 6 factors to rank proposals (see ILSRA-2001), but the winning entries areusually based on their science score

• Peer reviewers are typically unfamiliar with the realities of the ISS and Shuttle as a research platform

• The peer reviewers are used to the NIH model but NASA is not the NIH. The subject count, N is muchlower; the science platform (ISS and Shuttle) are far more complicated and unforgiving; and the costs andschedule and implementation restrictions are many

• While there is a “panel of technical experts from NASA and other cooperating space agencies” assigned toevaluate the feasibility of carrying out flight experiments according to the “relevance to NASA’sprogrammatic needs and goals,” they do their job after the solicitation process has chosen winners.

• The process seeks to be uniform and fair, stating that “all proposals will be evaluated for scientific andtechnical merit by independent peer-review panels,” but these panels use different standards in eachdiscipline. A winning score for a Behavior and Performance proposal might be 75, for example, while thatfor a Cardiovascular team could be 95

• The process seeks to be fair but an old boys network is still in place with many of the same investigatorshaving been around for decades. By favoring prior experience, the process throws a gauntlet in front ofnew investigators while “feeding the gravy train,” of the old ones. One experiment in Pharmacokinetics,for example, received a poor science score and failed to get in to a NASA NRA but snuck in the back doorwith a changed name the next year by the NSBRI.

The above issues are only half the problem. The other half is the confusion arising from the fact that there is notone NRA process but many and they confuse not only the principal investigators but the peer reviewers andNASA implementers overseeing them. The pyramid of Figure 6 is a gross simplification. In effect, there are 9separate solicitation mechanisms that lead to overlapping and conflicting experiments: NASA Flight NRAs;NSBRI Flight NRAs; CEVP Flight NRAs; NASA Ground NRAs; NSBRI Ground NRAs; CEVP GroundNRAs; SMOs; grants and unsoliticited proposals. In theory, these processes are somehow woven together, infact they are anything but.

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CPR.

The Critical Path Roadmap drives the direction and quality of the NRAs but it is flawed. In principal, this documentattempts to meet the goals of the Young Commission by means of risk reduction, mitigation, and management. Inpractice its reach far exceeds its grasp. Like a computer model of a complex system, its fidelity rests on the strengthof its underlying assumptions and its inputs. By carving the human body into 12 distinct disciplines, none of whichare really interconnected, the CPR attempts to do too much. Since the body is a complex system in which everysubsystem depends on every other one, the CPR ought follow the same philosophy. It does not. The CPR failsbecause it assumes that the PIs answering the fundamental questions in a particular discipline will be able to cull outthe cross-disciplinary effects from other disciplines. In fact, data sharing hurdles thrown in its path by astronautprivacy restrictions and other obstacles negate this assumption. The CPR is supposed to be a “living document” butthere’s not enough resources, human or otherwise, to change it fast enough to reflect program changes. Theconundrum of the CPR can best be appreciated by the following anecdote. A PI team proposing a cardiovascularexperiment was told they would have to downscale their study because cardiomyopathy addressed CriticalQuestions 3.06 and 3.18 under Critical Risks 13 and 14 of the CPR. This was of lesser importance (yellow andgreen) than the arrhythmia portion of their experiment which addressed Critical Question 3.01 of Critical Risk 13(Red). Their response to this was that “we are cardiologists who’ve been doing this for decades and we believearrythmias are caused by cardiomyopathy. The CPR is wrong,”

A second problem with the CPR is that the assignment of critical questions to particular experiments is a judgmentcall in many cases. For example, does the Merfeld Sensory Integration experiment, Critical Risk 33, address CriticalQuestion 9.09 or 9.25 or both; does the Alendronate SMO countermeasure (Critical Risk 9) also address CriticalRisk 10, and Critical Question 2.19, 2.98 and 2.06 or all of them; does Bungo-Levine’s CARDIO experimentaddress Critical Risks 13, 14 and 15, and Critical Questions 3.01, 3.06 and 3.18 or just the highest priority items(Red 1)? Figure 2 lists these overlapping critical questions and risks, and the consequence misjudgment can beserious. Take Oman’s VOILA experiment, for example, addressing Critical Risk 20 in Behavior and Performanceand labeled a Green 1 (lowest priority). It also appears to address Critical Risk 33 under Neurovestibular, however,which would elevate it to a Red 1, the highest priority. The difference between this label could be the differencebetween flying and deselection. Pierson’s SWAB experiment is another example, labeled as both an Immunediscipline, Critical Risk 22, and a Food/Nutrition discipline, Critical Risk 8; or Schneider’s TREADMILL, whichcuts across 4 disciplines, addressing Critical Risks 49, 19, 17 and 30 (at least it’s labeled a cross-disciplinaryexperiment). These are just some of the issues that are brought to bear when trying to use the CPR as a tool tocategorize and prioritize flight research experiments. Another problem with the CPR is its apparent disconnect withevidence-based space medicine, ie, observations gleaned from actual flight experience. The documented history ofphysiological problems lists behavioral problems and kidney stones as the most frequent and serious problems butthe CPR pays more attention to cardio and neuro while kidney stone experiments are ranked as Yellow 2 (RenalStone). And while behavior experiments abound in the flight queue (there are 5), there is not a proposedcountermeasure in the lot and redundant objectives in 3 of them. In summary, the CPR is a tool that attempts toextrapolate programmatic priorities using a cookbook approach to the human body that is prone to misinterpretationand confusion.

21

Confounding variables

The program has justified the use of a small subject size, N, through studies such as Evan’s and Ildstad’s SmallClinical Trials, which in the case of human life science flight experiments has subjects serving as their own controlsthough preflight, in-flight and post-flight data collection. The editors of this work, however, probably neverenvisioned the number of confounding variables that would negate a small N under spaceflight conditions. Figures8 and 9 are cases in point, showing the dispersion in two of the most important parameters in human microgravitystudies, aerobic capacity and bone loss. In the words of the one of the PIs, “The numbers are %change per monthwith SD in (). If you take +-3*SD as the range (contains 97% of the data), then you see the variability is huge. Forexample, for total femur trabecular BMD, the percent change is 2.5+-0.9, which means you have a range of 0 toabout 5% loss per month. At the end of 6 months, the extreme range is 30% or so of lost total femur trabecularBMD. These data clearly document large variabilities.”

How is one to determine the root cause of the data scatter in such studies when multiple parameters are varyingconcurrently, parameters that cannot be culled out due to data sharing issues (addressed later); different techniques orinstruments for measuring the same thing (Biopsy (US) vs Myon ( Russian); Profilaktika vs CEVIS; different types ofultrasound, DEXA’s, MRIs, etc). Throw the small N into the mix and conclusions of worth become rare indeed. How,for example, can one justify an N of 3 for the Foot experiment, 4 for H-reflex and 5 for Spatial Cues under suchcircumstances? The case of exercise countermeasures is especially noticeable, since they are supposed be beneficial onmultiple fronts, from muscle strength to bone loss. There are three exercise countermeasures on ISS, the TEVIS(treadmill), CEVIS (bicycle ergometer) and IRED (resistive force device). The exercise prescriptions used for all 3 wentfrom a research protocol to a countermeasure application before they were fully mature. The effect of exercise on thevarious organ systems is poorly understood as a consequence. Many assume that exercise is beneficial to bone loss, forexample, but more than one principal investigator has looked at Figures 8 and 9 and wondered how anyone could reachsuch a conclusion. And while the in-flight exercise countermeasure is mandatory, the exercise prescriptions vary greatly,oftentimes left up to the astronauts to do "their own thing." To compound matters, there are too many fingers in theexercise prescription pie: exercise physiologists, ASCRS, flight surgeons, etc. It is also interesting to note that theASCRS are under the auspices of Flight Surgeons, while the Exercise Physiology lab is under the Human Adaptation andCountermeasure Office, ie., flight research. The lab is also beholding to Med Ops since it responsible for a number ofmedical requirements (MRIDS). The concluding example relates to the use of drugs as a confounding variable and thelack of well-thought out exclusion controls. The soon to be implemented Alendronate study to reduce bone loss wouldhave used the same subjects eligible for other bone loss studies such as VIBE (using vibration) and Renal Stone (usingpotassium citrate) if the potential interactions had not been inadvertently detected. In short, a systematic, rigorous meansof preventing multiple variables from confounding flight research data is sorely lacking. The program is full of self-destructive inconsistencies, many of them owing to poor management (see below).

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Figure 8. Aerobic Capacity vs Flight Time, all increments

Results

QCT-Femoral neck QCT-Total femur iBMD tBMD cBMD cBMC iBMD tBMD cBMD cBMC

-1.4(0.7) p<0.0001

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neck

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-1.1 (0.8) p<0.01

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•Calculate percentage change in bone measures between pre- and •post-flight normalized by length of mission in months

•Percentage change per month (standard deviation)

•Significance of changes assessed with paired t-test (2-tailed)

Figure 9. Bone Loss data, all increments

% Change in Estimated VO2 Peak from Pre-Flight

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Management.

As should be obvious by now, many of the problems described above are nested in management. Figures 10 and 11speak volumes to the point. These charts read more like a plan for the invasion of Normandy than one outlining thesteps, organizations, boards and individuals involved in the process for developing countermeasures (Fig. 10) andmanifesting flight experiments (Fig 11). From the charts, the number of people involved are likely to be in thehundreds and the diagrams themselves are unreadable and unusable. Followed to the letter, these flow charts wouldinevitably lead to confusion. Another example is shown by Figure 12, describing the review board processexperiments must pass through. The sheer number of paths almost screams that “no one wants to make a decision.”When astronauts’ lives are at stake, ethics and informed consent review is essential, of course, but at some point itbecomes overkill. Take the case of alendronate again, a drug that has been in wide use for years with demonstratedbenefit for osteoporosis and bone loss. Having gone through one of the strictest regulatory systems on the planet, theFDA’s approval process for consumer drugs, it must still be subjected to the twists and turns of Figures 10, 11 and12 before it can be used in flight. By the time the Alendronate SMO gets through this gauntlet, no one will carebecause a list of bisphosphonates that could fill this page (and are already available) will likely have supplanted it onthe ground, every one of which will have to follow in its wake. Absurdity number one is that one decent study onthe pharmacokinetics of classes of drugs in microgravity might shortcut the process of requiring flight experimentsfor each individual drug by years, yet pharmacokinetics are called a Yellow 2 by the CPR and not even given toppriority, a point of great contention to many Medical Operations personnel. Absurdity number two is that those sameMed Ops personnel are able to prescribe drugs in orbit without knowing their pharmakokinetics. The system allowsit to happen both ways, has a lag time of years with an incalculable waste and confusion factor. The underlyingcause, in the author’s opinion, is a bureaucratic hodgepodge with NO CLEAR CHAIN OF COMMAND, and amanagement style operating by verbal rather than written orders, exasperated by an e-mail process that serves as themain organ of communication rather than formal memorandums. Everyone seems to have their hands in thedecision-making pot, and duplication runs rampant. The consequence? From the Select for Flight Telecons to thereview boards described above, action items are bounced back and forth between multiple codes, organizations andindividuals with infrequent resolution.

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CMflight

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Figure 10. Countermeasure Evolution

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OPERATIONAL RESEARCH BASIC RESEARCH

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•Increment Scientists (e.g., Incr. 1, 2, 3, 4, …..)•Mission Scientists (e.g., R2, STS-106, 92, 97, 98…..)•Project Scientists

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Figure 11. Solicitation-Manifesting Approval Process

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Figure 12. Review Board Processes

27

Typical of this “ping-pong” management” are the actions of one not-to be named review board emailing its membersnot to convene 48 weeks out of the year as opposed to informing them to convene 4. Memorandums ofUnderstanding and Project Plans also abound—how SK should relate to SM written by SM; how SM should relateto SK written by SK; a plan to merge 2 major organizations after they were unmerged following a previous merger.While many of these plans never reach fruition, there’s a tendency to ignore them even when they do since it’s asafe bet they’ll be amended before anyone can get comfortable enough to implement them.

Another manifestation of poor management is the time between an experiments’ selection and its first flight. Fromlimited data, the average waiting period for DSOs is 2.5 years, while that for ISS experiments is nearly 4 years, adelay that threatens the very foundation and utility of the experiment and tests the nerves of its PIs and flightmanagers alike. While extenuating circumstances such as schedule shifts, fleet turnaround times and accidentscertainly contribute to delays, part of the blame must rest with management. Then there is the problem ofconformance, ie., the number of crew members who actually sign up for an experiment after the crew briefing,shown for the DSO program in Figure 13.

Figure 13. Conformance in the DSO program

On a typical shuttle flight of 7 crewpersons, the participation rate has averaged only 1.9 subjects or a 28%conformance rate since STS-95 (Chart B, Appendix 2). The track record on ISS seems better, averaging nearly 50%,but that is deceptive since only 3 crewmen fly and 1.4 sign up. Poor conformance starts with the crew briefing, thepresentation given to each ISS or STS crewmember by the Principal Investigators. Often referred to as InformedConsent Briefing or ICB, the crew briefing is where informed consent agreements and confidentiality agreementsare obtained and BDC (biological data collection) schedules are baselined. Despite the fact that crew participation isessential to the success of the flight research program, the program is strictly voluntary and PIs must competeagainst each other for astronaut’s services. Allowing for the fact that subjects can be disqualified on medicalgrounds or excluded from some experiments because they’re mutually exclusive of others, the potential subject poolis lowered before it even starts. Then comes the crew time barrier. With less than 20 hours/week available forresearch (Figure 14), conformance is crippled again as it leaves from the starting gate. Next comes R+0, the 4 hourtime limit for landing day data collection, and the beat goes on.

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Figure 14. Crew time allotment

Med Ops

Medical Operations are distinct from flight research management yet so interwoven with it that they must be treatedseparately. Charts as convoluted as Figures 10-12 would be needed to show all the interactions (one has yet to bewritten, the challenge is so great). Although the primary goal of Med Ops is to maintain crew health and well-beingduring all phases of flight, they have many other responsibilities including:

• Medical Requirements Documents (MRIDS)• Crewmember medical selection and certification• Biomedical training on medical systems, procedures, and protocols• Pre-, in-, and post flight health evaluation and monitoring• Delivery of prevention, diagnostic and therapeutic care• Environmental health and monitoring• Crew countermeasure implementation• Emergency medical services• Crewmember rehabilitation and fitness evaluations

Though unintended, many of these responsibilities undercut the research program. The following examples illustrate thepoint :

o R+0: There is a 4 hour time limit on landing day (R+0) to collect biomedical researchdata. Of this, US Med Ops personnel has custody of more than half (2.25 hrs onaverage), taking 1 hour alone for the standard post flight medical exam. This leaves only1.25 hours for science at the most crucial time of data collection. R+0 is where therubber meets the road, the closest point of comparison between pre-flight 1 G data andthe still-fresh effects of microgravity upon immediate return. Despite its importance, datacollection must be compressed into a little over an hour. The process of doing so is a

29

scheduling nightmare, since all manifested experiments are competing against each otherfor time within that window. It taxes the PIs and BDC team to the limit every flight.

o Data-sharing: Astronaut privacy concerns scuttle the possibility of ready data transferbetween PIs. Such data exchange is needed to reduce the effect of confounding variables.Even without these concerns, there is no commonality of equipment on orbit or on theground, no attempt to work together to maximize science or reduce costs and timethrough sharing.

o The exercise protocol under the auspices of Med-ops is not tightly controlled. Althoughthe ASCRS work hard to generate individual exercise prescriptions, conformance is leftup to the crew and varies widely.

o Drugs are available and dispensed that can and will alter the effects of flight researchstudies. The list of available medications reads like an on-board pharmacy and the papertrail linking them to subjects participating in flight research experiments is not alwayswell documented.

o Medical Operations for Russian Cosmonauts are treated differently than US Med-ops forastronauts. These differences, as will be seen below, contribute to more inconsistencies.

Our Russian Friends

Although this too falls under the purview of management, it is so unique, that it must, like Med Ops, be addressedseparately. The Russians (and ESA) have their own Biomedical Researach Program, which, at first blush, issupposed to complement our own. But does it? Figure 15 lists Russian human flight experiments on ISS alongsidesome of their US counterparts. Many of these experiments appear to mirror our own with the whole being less thanthe sum of its parts. Cases in point: Russians don’t pay attention to the CPR and are doing experiments in severaldisciplines that may be duplicative; Russian crewmembers can participate in US experiments if we pay them, whileAmerican astronauts cannot participate in Russian experiments; some US PIs arrogantly think of Russianexperiments as “tissue paper” (Fitts, for example, who, it must be noted, has the largest cost per year of ANYexperiment on the manifest, and has an N of 3); Russians are not invited or choose not to attend the ISLSWGmeetings that select experiments from NASA NRAs, choosing their own peer review process for their experimentsin a way some NASA overseers view as inferior; the same precious space aboard ISS may be occupied by Russianhardware virtually identical to our own (the Russian experiment, Profilaktika uses a bicycle ergometer (velometer)while the CEVIS is available as well); Russians view the program with different priorities, choosingthermoregulation, (the experiment, Thermography) as a high priority while the US CPR ignores it, and so on. Life atESA isn’t much different. In the past month alone, 3 flight experiments suddenly appeared with requests formanifesting, one for blood pressure monitoring, another for EKG analysis (Rhythms) and a third for neurovestibularassessment (NeuroCOG), all remarkably similar to current DSO or HRF experiments. How many ways can onesplit the hairs of an EKG, one might ask, and how many varieties of 3-D visual imagery can one look at in the“name of science” without a countermeasure appearing? In a program with such limited resources, there shouldn’tbe many but there are. We may have a joint international crew but we do not have a joint research program. Theexpression, “A house divided against itself cannot stand,” comes to mind.

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Figure 15. Russian flight experiments/procedures vs selected US experiments

Title Discipline Origin Duration N Venue/Complete

H-Reflex Muscle US Long 4 Pre/In-Flt/Post-Increment 4Isokinesis Muscle Russian Long 20 Pre/Post ???Motor Cont Muscle Russian Long ?? Pre/Post ???Biopsy Muscle US Long 9 Pre/Post Increment 9Myon Muscle Russian Long 9? Pre/Post Increment 8?Sports Muscle Russian Long 9? Pre/Post Increment 8?

Mobility Neuro US Long/Short 18 Pre/Post Increment 8Equilibrium Neuro Russian Long ?? Pre/Post ???Sensory Neuro Russian Long 6? Pre/Post Increment 6?

Ep-Barr Immune US Long/Short 62 Pre/Post Increment 10Cytokine Immune Russian `Long ?? Pre/Post ???Chromo. Immune Germany Long 20 Pre/Post Increment 10Peradont Immune? Russian Long ?? Pre/In?Post ???

Xenon Cardio Netherlands Long 4 Pre/Post Increment 5ChemiLum Cardio Russian Long ?? Pre/Post ???Profilaktika Cardio Russian LongRhythms Cardio ESA ShortStability Cardio US Long/shortOrtho Intol Cardio US ShortMidodrine Cardio US LongTreadmill Cardio US Long Cardio Cardio US Long Card Control Cardio Canada Long( Xenon Cardio Netherlands Long

Renal Bone US Long/Short 20 Pre/In-Flt/Post, Incr. 10Diuresis Fluids/Kidney Russian Long 5? Pre/In-Flt/Post, Incr 5?

Thermogra Thermoreg. Russian Long 1? Pre/Post , Increment 4?

Interactions Behavior US Long 15 Pre/In/Post, Increment 8

EVARM Radiation Canada Long 9 EVAs Pre/In/Post, Increment 6

Bone Bone US Long 15 Pre/Post, Increment 9

Puff Respiration US Long 6 Pre/In-Flt/Post, Incr. 6

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Summary

There are many excuses some would cite for the poor performance described above: it’s a vestige of the old dayswhen operations led the food chain; the system is changing and it takes time to mature; ISS is in the build phase andresearch must await its completion; a flight platform is not a ground platform and one must live with confoundingvariables; a 3 person crew can’t perform like one with 6; STS 107 effected the schedule, and so on. While many ofthese excuses are valid, three facts stand out. The average experiment takes 5-6 years to complete, can cost asmuch as $4M and the avowed expectation of 3 experiments to flush out a single countermeasure in a particulardiscipline is pie in the sky. The more likely scenario, under the best of circumstances, is that when ISS has reachedthe end of its useful life, the number of countermeasures so derived will be pitifully small compared to theinvestment. Under the worst of circumstances, ISS will be in the ocean without a single red 1 countermeasure in thebooks for the cardiovascular, neurovestibular, pharmacokinetics, behaviour and other major disciplines. Then again,we could get lucky.

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3. RECOMMENDATIONS

Recommendations to the deficiencies of the current system will address near term, mid-term and long term needs,defined as 0-3 years, 3-6 years and 6-10 years respectively. All will involve changes to the areas discussed above,that is, the NRA process; the CPR; confounding variables, management, medical operations and the Russianrelationship. Specific recommendations for each area will be presented, as well as a new methodology to improvethe efficiency and effectiveness of the current program through the Moving Target Approach (MTA).

Near Term

As stated above, the current program has 45 flight experiments, 27 of which are low priority according to theREMAP guidelines for a balanced program (Appendix 1). More troubling is that the fact that only 4 of theseexperiments are countermeasures (all lower priority science) and the remainder show no clear path to new ones. Themost immediate short term need, therefore, is to “purge the pipeline” of irrelevant and extravagant science in orderto clear the way for higher priority studies focusing on countermeasures. The fastest way to do this purge is throughmanifesting and implementation. It will require a totally new approach, however, as the current process is ahodgepodge, grab-bag system with little rhyme or reason other than filling in empty slots on a chart. The executionof such an approach will not be easy since a painful transition is required and must be done within a narrow timewindow. The current stand-down caused by the STS 107 accident provides such a window, however. Like all otherprograms effected by the Columbia tragedy, Space and Life Sciences has an opportunity to rise above the ashesPhoenix-like so the loss of the crew will not be in vain.

MTA (Moving Target Approach)

A New Methodology for the Prioritization and Implementation of Flight Experiments

In the business world, profit is the difference between income and expense and return on investment is a function ofthe latter. In the world of human life science research, income is analogous to benefit and expense is analogous tocost and risk. Put another way,

ROI = F(Benefit) – F(Cost, risk)

ROI then, depends on the variables influencing benefit, cost and risk in the flight program. The process that followswill:

• Collect these variables into separate and distinct categories• Relate these categories to accepted metrics of performance• Populate these metrics with data from the current flight program and• Determine an overall “score” using the “moving target” approach.

The term “moving target” is used because the resulting score will shift with programmatic goals as they change. Inthe case to be described, the near term goal (0-3 years) will be to purge the pipeline to make way for more relevantexperiments; the midterm goal (3-6 years) will be to shift from the current NRA and CPR approach to a crossdisciplinary model that maximizes science and countermeasures and the long term goal (6-10 years) will be tooptimize management and cost control. This strategy is reasonable only because it is consistent with the currentclimate of a stable or escalating budget in life sciences research. If that climate shifts, however, the target can beshifted changes quickly. It has minimal inertia, enabling costs to be prioritized in the near term, for example, ormoving science and pipeline purging to later phases.

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Process

The process begins by combining the 30 or so variables that affect the flight research program (Figure 16) intocommon groupings. Without this simplification, the determination of a relative score or rank would depend on toomany parameters with nebulous measures of performance. The first order grouping is shown in figure 17 and resultsin the category regimes of Cost, Feasibility, Utility, Crew Considerations and Knowledge. These category regimesare then related to benchmarks in the flight research program that have established performance metrics. Thesebenchmarks are:

• Cost (replaces cost)• Countermeasure rank (replaces utility)• Completion date (replaces feasibility)• Conformance (replaces crew consideration)• Science rank (replaces knowledge)

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Figure 16. Variables affecting the human flight research program

V1=COST REMAINING—$V2=INITIAL COST—$V3=EXPLORATION CLASS EXPERIMENT (1 – 3 YR IMPACT TO PHYSIOLOGY)-UV4=LEO CLASS EXPERIMENT (0-1 YR IMPACT TO PHYSIOLOGY)--UV5= MIDDECK LOCKER EQUIVALENT VOLUME--FV6=NUMBER OF SUBJECTS REQUIRED--FV7=NUMBER OF SUBJECTS REMAINING--$, FV8=AVERAGE SIGNUP RATE PER EXPERIMENT/MISSION –C, FV9=NUMBER OF MISSIONS REQUIRED--$V9=CREW TIME REQUIRED TOTAL HRS--FV10=PI COSTS, IMPLEMENTATION COSTS--$V11=UP MASS--FV12=POWER REQUIRED--FV13=RELEVANCE TO FLIGHT PROGRAM--UV14=RELEVANCE TO BASIC SCIENCE--UV15=SCHEDULE FACTOR—$, FV16=CREW ANTHROPOMORPHICS, gender,etc)--CV17=CREW NATIONALITY (AMERICAN VS RUSSIAN VS ESA VS…)--CV18=DISCIPLINE RANKING--KV19=SPINOFF POTENTIAL TO POPULATION (MED, ENGINEERING, OTHER--KV20=SUPPORT CONSTRAINTS (LOCATION, PERSONNEL, ETC)--FV21=DUPLICITY FACTOR (TO OTHER EXPERIMENTS)--KV22=FLIGHT VS PROGRAM PRIORITIZATION--UV23=INTEGRATION COMPLEXITY--FV24=IMPLEMENTATION COMPLEXITY—F, $V25=INVASIVE VS NON-INVASIVE FACTOR--CV26=INHERENT LIMITION FACTOR (ROOKIE VS VETERAN, EVA, OTHERS)--CV27=IMPACT OF EXPERIMENT ON ISS OPERATIONS--FV28=FUDGE FACTOR (depends on program needs, goals, phase)V29=SKILL MIX—CV30=LANDING DAY SCHEDULE (R+0)-F

Note: U=utility category F=feasibility category C=crew considerations K=knowledge category

$=cost category

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Cost Science Countermeasures Conformance Completion date

Figure 17. Category Regimes

Utility • Programmatic *CPR score *Explor. Class *Leo Class

• Spinoffs Medical Detection Prevention Treatment Engineering

Crew Considerations • Briefing score • General interest(acceptability)

• Procedural complexity

• timeline

• Physical stress

• Crew characteristics(rookie, gender, int’l.Anthropom., other)

. Training

. Invasiveness, etc

• Sign-up rate

Feasibility • N/flt or Inc

• Flite Ops • Baselinedatacollection • HW / SW • Stowage

• Upmass

• Power • Crew time • Safety

• R+0 time

Knowledge • Science score

• Relevance(to flight prgmand BR&C)

Relevance tobasic science

• Redundancy(from LSDA,or experimentliteraturesearch)

Cost • Cost/yr

• Initial cost

• Number ofmissions

• Schedule

• N required

• PI costs

• Implem.$$

• N to finish

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Reading the Charts

The next step in the process is to create charts summarizing the performance benchmarks and populating them with metricsfor the current flight experiment program. This is shown in Appendix 2 for the Shuttle DSO experiments and the ISS HRFexperiments. There are 4 charts for each program for a total of 8. Charts A, B, C and D display Science andCountermeasure data; Conformance and Completion Date data, Cost to Complete data and Composite Rankingrespectively for the DSO program, while Charts E, F, G and H display the same metrics for the ISS HRF program.

Science and Countermeasure scores (Charts A,E)

Science scores are found by first determining the Critical Risks and Critical Questions from the Critical Path Roadmap(http://criticalpath.jsc.nasa.gov/) for each experiment (Figure 2) then fitting that data to programmatic prioritizations,such as the 5x5 charts of the Bioastronautics Critical Path Research Plan or the REMAP prioritization scale (Appendix1). This version of the MTA (Rev 1) will use the latter until the 5x5 charts reach a specified level of maturity as dictatedby the Office of Bioastronautics. In this process, the Science score is determined by assigning 1 through 6 from thehighest ranked Critical Risks on the REMAP priority scale to the lowest, i.e., red 1=1; red 2=2; yellow 1=3; yellow 2=4;green 1=5 and green 2=6. Due to the scarcity of Countermeasure experiments at this time, Countermeasure Scores aresimply based on whether or not the experiment is a countermeasure. Experiments with accepted countermeasures areshown with a CM designation in the CM/M column of Charts A and E and given a score of 2 if they are testing acountermeasure (highest score*); 4 if they are using a clinical/operational tool to evaluate the efficacy of acountermeasure or diagnostic test; or 6 if they are purely mechanistic with no clear path to a countermeasure (lowestscore). Relative rank of experiments with countermeasures is premature in the near term since there are too few. Thiswill change in the intermediate and far term phases when more countermeasures enter the pipeline. At that point, CMrankings will be based on Countermeasure Readiness Levels 1-9, as determined by the CEVP program.

The metrics for each Experiment Number, Title and Principal Investigator is shown in Chart A for the DSO programand in Chart E for the ISS HRF program.

Conformance and Completion Date score (Charts B, F)

Conformance (N/mission for DSOs and N/increment for ISS) is a measure of crew participation rate. It dependsupon protocol complexity, crew time, crew briefings, up-mass/volume, and the other factors of Figure 16. It is alsoone of the most important variables in determining an experiments success. Conformance is assessed by examiningearly, mid and recent program history, then determining a projected conformance rate through experimentcompletion. For the DSO program, metrics are examined for STS 95-107 (actual data) and STS 112-118 (projected).For the ISS HRF program, metrics for Increments 2-7 (actual data) and Increments 8-13 (projected) are examined.These data are used to estimate a projected finishing rate (usually midway between recent history and early history.New experiments with no historical data are given conformance rates similar to equivalent experiments as displayedin the Notes section of each chart.

Completion Date is the most critical parameter in the near term of the moving target approach, as will be explainedlater, and depends on the number of subjects required, the number remaining, the conformance rate, the number ofmissions or increments needed for experiment completion and the flight schedule (missions or increments/year).Subjects remaining (N to fin), is determined by subtracting N completed (actual data through flight completion, notR+360) from N required. The number of missions or increments remaining (Flts to fin or Inc (yrs) left) is found bydividing subjects remaining (N to fin) by conformance (N/flt or N/Incr). Lastly, a projected end date is found bydividing the missions remaining by the projected flight rate or increment rate/year to determine the estimated timeremaining and year/quarter of completion. The above data is shown for each Experiment Number, Title andPrincipal Investigator in Chart B for the DSO program and Chart F for the ISS HRF program.

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Cost Score (Charts C, G)

The cost of each experiment is found by multiplying its annual cost by the number of years for its projectedcompletion and adding in the cost of the reporting phase. As with conformance, cost is a function of many of thevariables shown in Figure 16, including Principal Investigator cost, implementation cost, number ofmissions/increments, schedule delays, etc. Charts C and G display the projected cost to finish each experimentstarting with Increment 8 in the ISS program and January 2005 in the DSO program (assuming STS flights will beon hold until January 05 due to the STS 107 accident).

Composite Score (Charts D, H)

Charts D and H summarize the above results for both the ISS and DSO programs, converting the raw data intoabsolute values that can be used to determine an overall score for Science, Countermeasure rank, Conformance, Costand Completion. In the case of Countermeasure Rank, Science Score and Conformance, the data is identical,displayed as a 1 (highest) to 6 (lowest) for Science and Countermeasure Rank, and as the projected number ofsubjects through experiment completion , N/flt or N/Incr, for Conformance. In the case of Completion Date, thedata from Charts B and F are converted to the number of quarters required to complete each experiment, startingwith increment 8 for ISS and January 05 for DSOs. Finally, in the case of Cost, the key metric is annualized toCost/year on a scale of 0 to 1. This is determined by multiplying the annualized costs in Charts C and G by 10-6 toderive a 0-1 scale representing an upper limit of $1M. The composite results of Charts D and H will now be used todetermine an overall score and rank for each program based on the near, mid and long term emphasis of the movingtarget approach.

Moving Target Approach

The basis of the Moving Target Approach (MTA) is that goals tend to shift in cycles which will have a profound effect onthe execution and cost basis of any program. The REMAP committee’s shift from Exploration Class mission priorities(5x5) to 180 day Balanced Program priorities (5x5) in the Human Life Science Flight Research program provides a goodexample. It caused an associated shift in the priorities of the Critical Path Roadmap. Another example is the effect STS-107 or the Challenger accident might have on the experiment complement. The same holds true for budgetary constraints.A stable or escalating budgetary climate such as currently exists for BR&C results in an entirely different approach thanone of fiscal cuts. The MTA can take such shifts into account by changing the basis of the scoring function that will rankand prioritize flight experiments. In general, the scoring process consists of a) defining an envelope that encompasses thescoring range of all experiments, and b) determining where in the envelope each experiment actually falls. The upper andlower bounds of the envelope are determined by a primary criterion, whereas placement within the envelope is decidedfrom secondary criteria using the analytic hierarchy process or AHP discussed below. Designation of criteria as primary orsecondary depends on the programmatic phase or priority as follows:

Phase primary criterion secondary criteriaNear completion time countermeasure level, scientific value, conformance, costMid (1) or countermeasure level completion time, scientific value, conformance, costMid (2) scientific value countermeasure level, completion time, conformance, cost

Long cost per year completion time, countermeasure level, scientific value, conformance

In general, the scores for each phase are not chronologically constrained, and are calculated by:

Near Term Score = fn (Completion Time) for the near termMid Term Score = fm (CM or Science) for the mid termFar Term Score = fL ( Cost) for the long term

The determination of these scores, based on the above criterion will now be discussed.

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Near term phase (0-3 years)

The near term phase is designated as 0-3 years but can be shorter or longer if deemed appropriate. For the currentprogram, the most immediate short term need is to “clear the pipeline” of less relevant science in order to make wayfor better experiments in the future (mid term phase). In this climate, completion time is the most important criterionand scores will be calculated as a function of the quarters to complete variable from Charts D (DSO) and H (HRF).The score for a particular experiment is then:

Near Term Score = fn (Comp Time), where Completion Time= fA(Science, CM, Conformance, Cost).

Stated another way, the near term score for each experiment in the current (or soon to be expected) manifest queuewill be determined from the number of quarters it requires to complete (primary criterion), with Science score,Countermeasure rank and Cost playing the role of tiebreakers (secondary criterion). The tiebreaker function, fA, isdetermined through the Analytic Hierarchy Process (AHP), which uses pairwise comparisons to make qualitativeand quantitative decisions in a “reasonable” way (reference: Saaty, Thomas L. Multicriteria Decision Making: TheAnalytic Hierarchy Process. 1988). The basis of AHP is the assignment of values based on the relative importanceof 2 criteria at a time, then using those values to derive weight factors for the respective independent variables, inthis case, CM, Conformance, Cost and Science. If any 2 variables, Aand B, are compared to each other in such a4x4 matrix, a 1 would be assigned if they were about equal in importance; a 3 if A was slightly more important thanB; a 5 if A was definitely more important than B; a 7 if it was strongly more important and a 9 if it was criticallymore important (the reciprocal is used if B is compared to A). In the case of the near term phase, the matrix derivedin this way is as follows:

Figure 18. AHP results for near term

Key: 1 = A and B are about equal in importance 3 = A is slightly more important than B 5 = A is definitely more important than B 7 = A is strongly more important than B 9 = A is critically more important Note: the reciprocal is used when B is compared to A

Although the values are subjective, there is inherent reasonableness to the process in that for the near term, whenclearing the pipeline is paramount and completion time is the independent variable, the tiebreaker hierarchy would becountermeasures, science, conformance and cost in that order. Cost carries the least important weight because BR&C isin a cost-stable environment at the moment. Conformance is next to least in importance because it’s already been taken

sc cm conf cost

sc 1 1/3 5 7

cm 3 1 5 7

conf 1/5 1/5 1 5

cost 1/7 1/7 1/5 1

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into account in computing the completion date (N/flt or N/Inc), so its only other effect is secondary ( i.e. crew briefing,up-mass, stowage and the other variables of Figure 16). That leaves Science and Countermeasures with Countermeasuresranked ahead simply because there are so few at this time that getting answers to any of the critical questions or riskswould be a great success. The fastest completion of experiments with countermeasures, even those with average sciencescores makes sense since this is the quickest way to get new high priority countermeasure experiments into the pipeline.As discussed previously, this hierarchy and the weight factors derived from it reflect only the current climate and willchange in the mid and long term phases, or if program goals change (i.e., exploration vs. balanced program).Furthermore, unless one variable is drastically more important than another, the relative weights derived from thisprocess will not appreciably affect the outcome, and it will be “reasonable”.

Once the matrix values above are determined, the AHP process uses them to compute the relative weights of the science,countermeasure, conformance and cost scores (w1, w2, w3, w4) used in the secondary criteria. These are then used tospecify fA. Specifically,

fA (Science, CM, Conformance, Cost)= w1* S + w2 * CM + w3 x Conf + w4 * Cost 0<fA<1

With fA finally specified, the final score can now be determined for each experiment from the data of Charts D and H.

The computation proceeds as follows:

In step a, the scoring envelope is found from the variable, theta, which defines the upper and lower bounds of thescoring function. It is determined by the user’s answer to a simple comparative question (see below). In Step (b),weights from the AHP matrix are applied to each experiment’s normalized secondary criterion scores and used to find aninterpolation factor r that determines how close to the upper and lower bounds of the envelope the experiment’s scoreactually is. Mathematically, the score is expressed as:

Near Term Score= e-(theta*q)

where q is the number of quarters to complete an experiment from Charts D and H and theta= )1( rr -+q q.

The interpolation factor, r, reflects the overall worth of the secondary criteria in the near-term. In this case, r = 1 reflectsthe most favorable and r = 0 the least favorable set of secondary criteria (countermeasure level , scientific value,

conformance, and cost, respectively). To obtain the values of q and q above, the user is instructed to answer questionssimilar to the following:

“If an experiment took 10 quarters to complete and all its secondary criteria were optimal, how many more quarters wouldit have to take for the value of the experiment to be reduced by 50%?”

“If two experiments take 5 quarters to complete, and one has all secondary criteria at their highest level and the other hasall secondary variables at a minimal level, how much better is the first experiment than the second?”

The answers to such questions are then used to produce the equations that solve for q and q: With the latter sodetermined, and the weights (w1, w2, w3, w4) and r value found from AHP, the upper and lower bounds of thescoring envelope and the placement of each experiment’s score within that envelope can now be found. This isshown conceptually in figure 19, which shows the envelope, and Figure 20, which shows how an experiment withthe same completion time can get a progressively lower score as its secondary criteria suffer (in this case, CMlevel, science, cost and conformance). All calculations are embedded in a user friendly format linked to thequestions in an Excel program (see Appendix 3). While the answer in many cases is a judgment call, the relativescores between experiments rarely changes unless there is a clear and substantial difference between them.

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Figure 19. Upper and Lower Bounds of Primary Criterion (Completion Time)

theta0 = 0.35 p = .20

scor

e en

velo

pe

quarters to complete1 2 3 4 5 6 7 8 9 10 11 12 13 14

0

.2

.4

.6

.8

1

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Figure 20. Conceptual Dependence of Primary Criteria (completion time) on Secondary Criteria

theta0 = 0.35 p = .20

scor

e

quarters to complete1 2 3 4 5 6 7 8 9 10 11 12 13 14

0

.2

.4

.6

.8

1

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RESULTS:

THE BOTTOM LINE: “You Got To Know When To Hold Em’, and Know When To Fold Em’ “

The above analysis was a demonstration of how the Moving Target Approach can be used to prioritize flightexperiments for the Shuttle and ISS programs as a function of near, mid and long term program goals. Theanalysis assumes a certain clarity of such goals, in this case a clearing of the manifest for the short term; anemphasis on countermeasures and science for the mid term; and an emphasis on costs for the long term.Figures 21 and 22 show the results of this analysis applied to actual data in the near term, and the ranking ofexperiments that follow.

DSO experiments

near

-ter

m s

core

quarters to complete0 5 10 15 20

0

.5

1499

637 635E011

636490B504

632B493 503S

TBD633639498

TBD634

500

Figure 21. DSO scores vs completion time

DSOs: The results show that DSOs 499, 637, 490 B and EO011 (EVARM) should be given the highestpriority in the flight manifest, while DSOs 635, 490B and 503S should receive the next highest priority. Allof these experiments should be completed as quickly as possible. Conversely DSOs 500, 633 and 634 all haveconformance/performance issues causing untoward delays and should be considered for possible de-selection.DSO TBD (Merfeld) is new and hasn’t entered the pipeline yet so the number of quarters is expected to belarge but its score is still relatively low.

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HRF experiments

near

-ter

m s

core

quarters to complete0 10 20 30

0

.2

.4

.6

.8

EO83

EO96

E046

E104

nsbri 00

E318EO57E400

E343

E120

E129

Figure 22. HRF scores vs completion time

HRF: The results show that experiments EO 343, 096, 083 and 057 should be given the highest priority in theflight manifest, while EOs 400, 120 and 104 and 318 should receive the next highest consideration. All ofthese experiments should be completed as quickly as possible. Conversely NSBRI experiment 009(Psychosocial), and E0s 129 (Epstein Barr) and 046 (Cardiac) all have conformance/performance issuescausing untoward delays. Though some are new (009 and 046) and haven’t been manifested yet, they shouldstill be scrutinized and considered probationary.

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Mid Term

The mid- term phase is designated as 3-6 years but can be shorter or longer if deemed appropriate. During thisphase, it is assumed that the pipeline has been cleared and filled with relevant science with an unquestionedemphasis on countermeasures. The dilemma is how to get there from here. To have relevant science andcountermeasures available by the end of the 3 year near term phase requires a major facelift to the underpinnings ofthe existing program. These underpinnings consist of the NRA process, the CPR and program management, and thechanges must begin at once.

NRA

There is no way to candy coat this, the flight NRA should be scrapped. The connection between solicited proposals,program relevance, and the realities of the flight program are too tenuous to make it work. The source of flightresearch experiments should instead come from the much larger ground analog program which employs, NRAs,SMOs, NSBRI and other grants as venues. Ground NRAs should emphasize countermeasures and clearly defineobjectives (a sample NRA is provided in Appendix 4. In addition to eliminating the flight NRA and modifying theground solicitations, the pyramid of Figure 6 should reflect an interdependence of relevant ground basedinvestigations bubbling up through the CEVP program instead of taking unrelated paths. Final selection of suchexperiments from ground to flight should be done via an expedited DARPA-like process without the inertia of thecurrent system. In this process:

• Focus areas are identified by a Lead Project Manager

• Workshops are held on these focus areas with controlled attendance

• Solicitations are generally made by BAAs (Broad Agency Announcements). Announcements are published inTHE COMMERCE BUSINESS DAILY or similar venues

• .White papers are solicited from interested parties

• Quick response follow-ups to the white paper either recommend or discourage submission of a full proposal.THE TYPICAL RESPONSE TIME VARIES FROM TWO WEEKS TO A MONTH AS SPELLED OUT IN THEBAA.

• Review of proposals is performed by government employees only (generally but not limited to DoD personnel).Reviewers use specific criteria, some of which are identified in the BAA. PROPOSAL REVIEW TIME ISSPELLED OUT IN THE BAA AND CAN BE AS SHORT AS A MONTH AND UP TO THREE MONTHS

• Final Selection is in the hands of the Focus Area Program Manager. Discretion is based on "program needs".

• DARPA MAY FUND SEVERAL COMPETING PROJECTS FOR A LIMITED AMOUNT OFTIME/DOLLARS THEN WEED OUT THE BEST AND INCREASE FUNDING TO THE SURVIVOR

• Feedback is limited. Categorized as: (a) fundable with funds available, (c) fundable with funds uncertain, (c)fundable with no funds, (d) not fundable

In the process desribed above, the white paper results in a better proposal since the initiator recognizes it will betaken seriously and it also reduces the governments’ work. The DARPA program manager has exceptional breadthin selection and execution since he or she is evaluated based on the productivity of the overall portfolio. Unlike thecurrent NRA peer review process, this limited oversight approach cultivates a quick-moving, robust, productive andrelevant program. Traditional peer review should be left to the ground program, not flight.

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CPR

This tool needs to be drastically overhauled to reflect the realities of the ISS and Shuttle flight platforms. Multipleexperiments from the same discipline with confounding variables and poor controls is not the way to harvestproductive countermeasures. Currently, the CPR drives the NRA but without a flight NRA, its usefulness would beconfined to the ground NRA. One possibility is to merge it with an evidence-based space medicine office. Such anoffice, under the direction of Dr Jonathon Clark with input from Dr John Charles and the NSBRI, for example,would effectively integrate the CPR into a responsive and robust organization whose job would be to strike acompromise between the old CPR goals, actual flight observations and programmatic priorities. This office wouldsolicit input from the NSBRI and other investigators to shape the content of the ground NRAs. The NRAs wouldthen focus on identified operational constraints instead of traditional physiological disciplines. Such an arrangementwould place the human as a subsystem in the flight operations program rather than as a unique exception to it. Itwould place the physiological alterations related to space-flight in the context of their operational implications. Forexample, postflight egress has been regarded as a significant operational problem after long-duration spaceflight.Inability to egress is caused by disturbances in sensorimotor, cardiovascular and muscular function. A multi-disciplinary team could address the various components underlying egress capability in a more integrated fashionthan does the current system. This concept could carry over to other operational issues such as landing performance,EVA etc. This operational team approach would focus the research questions and foster inter-disciplinaryinteraction. It is only through such interdisciplinary interaction that we will be able to develop integratedcountermeasures that address changes in multiple physiological systems

PROGRAM MANAGEMENT

Aside from the NRA and CPR, a majority of the barriers to an effective and efficient flight research program come frommanagement insufficiencies. These insufficiencies reside in many areas, subtle as well as obvious, and only the mostobvious will be discussed here with some possible solutions. They are: confounding variables, data sharing, the crewbriefing, R+0, the Russian problem, medical operations, payload operations and flight manifesting.

Confounding Variables

Under the best of circumstances, even with a revised NRA, CPR and relevant experiments in the pipeline, the usefulnessof the flight program would still be highly suspect due to low N’s and confounding variables. As stated at the onset, the“we have to live with it, that’s the nature of the beast,” mantra has become endemic and part of the culture. It must beeliminated and science must be taken seriously. More seriously than the handing out of grants to familiar institutions;more seriously than randomly filling in manifesting slots; more seriously than chaotically dispersing unobligated fundinglines and more seriously than implementation concerns of schedule, up-mass, volume and a dozen or more otherchokepoints from R+0 to ceremonies at the runway to overly time consuming physical exams. The first place to start isby devariable-izing the mix. If exercise effects bone loss, it must be removed as a factor in drug or vibration studieslooking at bone loss; if uncontrolled exercise prescriptions effect studies of muscle strength, aerobic capacity, enduranceand thermoregulation, participating subjects must have tightly controlled protocols; if electrolyte balance and weight losseffects cardiac function, both must be eliminated as variables in cardiovascular studies and so on. Not all experiments aresusceptible to confounding variables in the same way, however, and it is useful to list the degree of susceptibility.Discussions with various investigators, internal and external, led to the “proneness” index for each discipline and“confounders” list shown in Figure 23.

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Figure 23. Proneness Index and Confounders

The purpose of this “proneness index” is to focus attention on experiments whose results are more likely to be biased byuncontrolled parameters (“confounders”). Once identified as such, PIs would emphasize the removal of suchconfounders from their protocols . One might ask why this can’t be done by post flight data reduction, therebysimplifying the protocols. After all, the grouping of data sets with similar conditions is done all the time on the ground, isfar simpler than tight in-flight controls and could just as easily eliminate or minimize confounding effects. There are 2reasons. The first is that the small N size on ISS and Shuttle precludes a population big enough to make such groupings.The other is data-sharing issues.

Data-sharing

Data sharing is like an appendix, a vestigial organ left over from NASA’s cave man days. Astronauts are supposed to besubsystems in today’s NASA, but like it or not, they still stand atop the food chain and their privacy rules are like thebible. Example: a PIs request for an ISS crewmember’s body weight was denied on the basis of it being privilegedmedical data, thereby preventing him from understanding the effect of body mass on impact load, the very purpose of hisexperiment. Body weight? The same body weight on everyone’s driving license and passport? Privacy restrictionsabound, they’re icebergs confronting the Titanic, sabotaging any hope of eliminating confounding effects. How can PIshope to work together when the system won’t let them? The recommendation: Remove censorship from the purview ofmedical operations. An independent board with research science and crew presence should make all data-sharingdecisions and the onus should be on proving why data shouldn’t be shared, not why it should.

Even if data sharing ceases to be a barrier to confounding variables, the idea of PIs sharing information is still an alienconcept. Aside from that, the system still discourages sharing because experiments with similar objectives are rarelymanifested together. Taken together with the vagaries of the CPR, which cause overlapping experiments addressingmany of the same Critical Risks and Critical Questions, the inevitable results; exorbitant costs and duplicative science.To appreciate the extent of this problem, and its possible solution, the following example in the cardiovascular disciplineis cited:

Discipline Degree of Proneness Confounding Variables from Other Disciplines

Cardiovascular High Exercise, diet, electrolytes, drugs, HR recovery time

Neurovestibular Exercise, sensory motor disturbances, biopsies

Bone High Exercise, drugs, diet, muscle changes,marrow changes, genetics

Muscle High Bone changes, drugs, Cardio effects

Pharmacokinetics High Stress, diet, drugs, electrolyte/plasma urine pH,exercise, body wt, plasma protein, cardiac output,bloodflow, hormones (cortisol, DHEA, sex hormones,urinary creatinine clearance, herbals/homeopathics

Immune System

Behav/Performance High Premeditated masking

Food/Nutrition High Exercise, stress (behavior), drugs, psychosoc. ImmuneRadiation (s. smith)

Radiation

Toxic Exposure

Multi-system Low

Clinical Operation Low

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Cardiac Control (Hughson, E117) is a Yellow 2 on the flight priority scale, addressing Critical Risks 14 and 15, andCritical Questions 3.05 and 3.17 (reference Figure 2). Although its objectives of assessing the arterial baroreflex areunlike those of CARDIAC (Bungo/Levine, EO46) investigating cardiac arrhythmias/myopathy, or STABILITY (Cohen,NSBRI #TBD) addressing orthostatic intolerance and T-wave alternans, all 3 experiments, as well as a new SMOproposed by Dominick D’Aunno and Rhythyms, a proposed ESA experiment, address the same or similar risks andquestions. Furthermore, all 5 have related goals and collect similar data from similar hardware or software (12 leadECGs; detailed cardiovascular models such as CSI, ARMA and TWA, and hemodynamic measurements of strokevolume, compliance, peripheral resistance, Q-T, R-R segment analysis, etc). Since the parameters, tools and techniquesinvolved are overlapping in many examples, combining resources with respect to data-sharing, hardware, and resources,if not subjects makes sense and could result in a considerable savings in time, cost and training. Such a savings couldbe accomplished through the Experiment Commonality Matrix approach shown in Appendix 5. In this approach, likeexperiments would be manifested on the same increments or shuttle flights with the PIs utilizing common parametersderived from conduits to common hardware. In the boiler plate provided, Sheet A lists science and implementationcommonalities, Sheet B lists data parameter commonalities and Sheet C lists hardware commonalities. Two specificexamples are shown following the boiler plate to demonstrate how this might be done for cardiovascular andneurovestibular experiments, with common hardware and data parameters checked off in each. In some cases it mayeven be possible to use the same hardware for experiments from disparate disciplines, such as Lang’s Subregional Boneand Cohen’s Stability, both of which use MRIs and could be manifested together if the same subjects were encouraged tosign up for both. Before such a Commonality Action Approach could be implemented, questions would need to beaddressed beforehand by the relevant PIs such as the following for cardiovascular experiments:

• Can they share the in-flite holter• Can they share the same 12 lead ecg system pre in and post flite,,,,if not, why not?• Since T wave alternans is fundamental to B/L and Hughson, would Hughson’s experiment benefit by its

use as well. If so, all PIs should agree to data-share• Cohen’s Cambridge heart machine has a T connect, so all PIs should be able to share 12 leads• Inflite measurements of confounding variables such as drugs or electrolyte balance are very important, as a

possible cause of prolonging the QT interval. Can all the experiments add measurements of K, Mg and Caand Na (especially K and Mg) if the PIs agree?

• Other parameters, especially invasive measurements such as CVP that discourage participation rates andreduce N would also benefit greatly by a combination strategy

If such issues can be addressed positively with the PIs working together to fill in the blanks, they could be manifested inthe same timeframe to the benefit of all. Oversight of this function may fall under the purview of a “CommonalityBoard,” whose job it would be to bring disparate PIs together with the objective of arranging data sharing of hardware aswell as subjects. Such a board could be an offshoot of the same independent data sharing board discussed above.

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The Crew Briefing

Given the importance of the crew briefing as a choke point (discussed earlier), steps should be taken here to insuremaximum conformance. One recommendation is to designate an Experiment Coordinator (EC) from the AstronautOffice to bridge the gap between the flight crew and the PIs. The EC, preferably with a medical or researchbackground, could deliver a pre-briefing prior to the actual ICB, preparing the crew beforehand for the formal PIpresentations. This would foster more relevant information exchange than the current format, which compels thePrincipal Investigators to compete against one another in “selling” their individual experiments within 15 minutes.Other recommendations regarding the ICB:

• Mission or Increment Scientist leads discussion• Introductory remarks kept to a minimum (5 minutes or less)• 10 minute maximum per PI presentation• 10 viewgraph limit per PI presentation• What, why, when and where format• Show how experiment will benefit the crew and the public at large• List crew constraints of each experiment (food, drugs, motion, invasive procedures, etc)• Show number of subjects required to complete an experiment• Show number of subjects completed to date for each experiment• PIs or designated Co-Is must be required to attend the ICB• No discussion of rank order prioritization• Controlled attendance limited to presenters, PIs, flight surgeon and need to know individuals• Formalized Debriefing required within 12 months of crew return

The Russian Problem

As previously elucidated, data collection and sharing are not equal and bi-directional with the Russians, despite bi-lateral agreements to the contrary,. This issue is part of a much larger and more serious one--flight experiment non-cooperation. The consequence of this disconnect is a redundant, wasteful and illogical imbalance in the flightprogram. One reason for this is a lack of consensus among NASA’s international partners on the content andappropriateness of our NRAs, CPR and MRIDs/CSEs (Medical Requirements Documents/Clinical StatusEvaluation--the collection of pre/post measurements used by Med Ops personnel to assess the physical well-being ofreturning crewmembers). The Russians do not feel compelled to participate in many of these processes for a varietyof reasons. Among others-- they feel NASA is biased because it insists on more stringent limits on astronaut crewtime than that of their cosmonauts; they claim some US PIs believe Russian data collection is inferior; they feel thatdifferences in financial compensation justify Russian crewmembers being paid to participate in US experiments.The solution to such opposing points of view is difficult, especially since there is a cultural component. It willrequire trust, policy change and true bi-laterality. It will also take time and the familiarity it breeds, which may bethe saving grace. The recently completed Increment 6 mission where the crew landed hundreds of kilometers awayfrom their target in the steppes in Russia is a hopeful sign of progress. Despite the difficulties of shipping equipmentthrough customs, getting Russian participation on many bureaucratic fronts and integrating a complex program ofdata collection and joint operations, it went extremely well. Perhaps in the end, the workers in the trenches willsolve this problem on their own.

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Medical Operations

As discussed earlier, Med-Ops and the flight research program cross paths at many points, not all of them in apositive way. The most serious crossovers are in the areas of crew countermeasure implementation; pre-, in-, andpost flight health evaluation; delivery of prevention, diagnostic and therapeutic care; and crew rehabilitation andfitness evaluations.The countermeasure implementation issue is particularly instructive because it is so rooted in the medicalestablishment. Med Ops policy dictates that participating subjects in medical experiments cannot be used ascontrols if it means denying acknowledged countermeasures to an existing medical condition. In general, this isethically and morally correct, as in the case of a heart or kidney medications, but not universally. Take the case ofexercise countermeasures aboard ISS, where exercise was deemed a “mature countermeasure” before its effect onbone loss, muscle strength, aerobic capacity, sweating and electrolyte loss could be fully understood. As aconsequence, experiments attempting to understand these effects are befit with problems because Med Ops will notpermit the exercise protocol to be reduced, standardized or eliminated for the benefit of such research.Quantification of such conflicting variables are not possible in flight. One might question the wisdom of such ablanket rule, considering that astronauts and cosmonauts have participated in long duration missions withoutcontrolled or enforced exercise programs in the past. (Neil Armstrong used to eschew exercise, quipping we all havea certain number of heartbeats in our lifetime and he wasn’t about to waste some of his on exercise. Clinton Rubin, aleading PI in the bone loss area has questioned whether exercise effects bone loss in space at all.) In light of thisloggerhead, what to do? If the Med-Ops policy cannot be changed, which seems likely, the only reasonablealternative is to deduce the above interactions from ground studies.

If exercise is one countermeasure whose premature “maturity” has “decked” the flight research program, drugs areanother. Stories of uncontrolled drug use are more rumor than fact but that does not alter the effect medicationsmight have on the results flight experiments. If the definition of drugs is arbitrarily extended to include nutritionalsupplements, electrolytes, even caloric intake, the problem multiplies. More than one investigator believes thatdisparities in the condition of returning long duration crewmembers can be traced to imbalances in caloric and fluidinput/output rather than to innate decrements in physiology caused by microgravity. The solution in this case, cannotbe tighter drug use controls, since these are already in place. Instead, it may hinge of resolving nutritional,electrolyte and fluid imbalances on a daily basis for each crewmember. Another crossover issue involves theAstronaut Strength and Rehabilitation Specialists (ASRS). Under the purview of Medical Operations, the ASCRSdispense exercise prescriptions to the crew without realizing the effects of such Rx’s on flight experiments. Toalleviate this choke point, it is recommended that this function be transferred to the control of the exercisephysiology laboratory and the flight science program.

R+0

The Russian issue reduces the effective subject pool because cosmonauts are treated differently than astronauts; MedOps decisions have the same effect due to policy inconsistencies that cause confounding variables, and NASAmanagement does its part by encouraging ceremonies on the runway or family visits following landing. They allcome together at R+0 to conspire against the success of each experiment. With some variation, data taken withinhours of landing is important to every discipline according to a query of PIs (see Appendix 6). This is especiallysignificant given the sensitivity to N, the number of subjects. To lose subjects because of R+0 constraints defeatsthe very purpose of the flight research program. Just what are these constraints and how might they be removed?The simple answer is to give R+0 the priority it deserves and focus all available resources on it. If that meanspostponing ceremonies and family visits until after the first BDC session, so be it. Beyond that, solutions are not sosimple. Extending the 4 hour time limit more than an hour is not practical, since the crew has already been up forover 16 hours preparing for reentry and is in great need of rest. One possibility is to put a 16 time limit on thenumber of hours the crew has been awake in preparation for TIG (time of ignition for deorbit) instead of 4 hoursfollowing touchdown. Another is to reduce the post flight physical and Med Ops time in favor of BDC time. A timessavings lesson could be learned from the Russians as well. Their physicals take 30 minutes instead of 1 hour andthey spread their Med Ops procedures over days instead of cramming them into R+0.

Payload Ops

50

NASA is traditionally an operations-oriented agency, and the primary interface of human flight experiments with theoperational side of the house is at the payloads level. As far as Engineering is concerned, flight experiments meanupmass, mid-deck locker volume, downmass, schedule and little else. At that level, experiments must compete withevery other bit of hardware and software bound for or from ISS, and the competition is steep. The problems withTEVIS, CEVIS and IRED are typical. Hardware updates, maintenance and repairs have been delayed many timesover and this trend will likely continue as long as human flight research is given second shrift compared to OPSrelated hardware. It may well be that until such time as ISS has reached core complete with 6-person crews, theexperiments will lose out and nothing can be done about it.

Manifesting

Whereas manifesting in the near term was designed to purge the pipeline for new and better experiments, manifesting inthe mid term assumes the pipeline has been cleared and filled with relevant science. The focus then turns to how best tooptimize the resulting countermeasures. The Experiment Commonality Matrix discussed under data sharing was onemethod of doing so, the other is by use of the MTA.

MTA

The manifesting of experiments in the mid-term must be done differently than in the near term, which was designed topurge the pipeline for new and better experiments. Manifesting in the mid term assumes this has been accomplished andthat science and countermeasure value are the most important parameters. Mid-term scores are then calculated as afunction of countermeasure level (primary criterion) and science score, completion date, conformance and cost(secondary criteria). In other words, the score for a particular experiment,

Mid Term Score = fm (CM), where Countermeasure= fB(Science, Conformance, Cost, Completion Time).

Stated another way, the score for each experiment in the mid term phase will be determined by its Countermeasurevalue, with Science score, Conformance, Completion Time and Cost in that order acting as tiebreakers. As before,the tiebreaker function, in this case, fB, is determined through the Analytic Hierarchy Process (AHP), which usespairwise comparisons to make qualitative and quantitative decisions in a “reasonable” way. In the mid term phase,the matrix so derived is:

Key: 1 = A and B are about equal inimportance

3 = A is slightly more important than B 5 = A is definitely more important than B 7 = A is strongly more important than B 9 = A is critically more important Note: the reciprocal is used when B is compared to A

Figure 24. AHP Results for the Mid Term

sc c.date conf cost

sc 1 5 5 5

c.date 1/5 1 1/5 3

conf 1/5 5 1 5

cost 1/5 1/3 1/5 1

51

Again, the values are subjective, but there is inherent reasonableness to the process in that science is the most importantparameter when judging countermeasures, followed by conformance, which drives completion time, then cost. Cost isthe least important variable in this outcome only as long as BR&C is in a cost-stable climate. With the matrix valuesshown above, the AHP process computes relative weights for the science, completion time, conformance and cost (w1,w2, w3, w4), which are then used to specify fB, where:

fB (Science, Completion Time, Conformance, Cost)= w1* S + w2 * CD + w3 x Conf + w4 * Cost 0< fB <1

With fB specified, the Mid Term Score can be determined for each experiment from the data in Charts D and H:

The computation proceeds as before:

In step a, the scoring envelope is found from the variable, theta, which defines the upper and lower bounds of thescoring function from the user’s answer to simple comparative questions (see below). In Step (b), weights from the AHPmatrix are applied to each experiment’s normalized secondary criterion scores and used to find an interpolation factor rthat determines how close to the upper and lower bounds of the envelope the experiment’s score actually is.Mathematically, the score is expressed as:

Mid Term Score= e-(theta*CM)

where CM is the Countermeasure level for an experiment and theta= )1( rr -+q q. The interpolation factor, r, reflects

the overall worth of the secondary criteria in the mid-term. In this case, r = 1 reflects the most favorable and r = 0 theleast favorable set of secondary criteria (science score, completion time, conformance, and cost, respectively). To obtain

the values of q and q above, the user is instructed to answer mid-term oriented questions such as,

“If an experiment has a perfect mid term score of 100 with its countermeasure value at 1 (highest) and peak values ofscience, conformance, cost and completion time, how much worse would its countermeasure value be if its mid-termscore was 50?

“If 2 experiments have the same high countermeasure value but one has peak secondary criteria for science,conformance, cost and completion time while the other has the lowest values of same, how much better is the firstexperiment than the second?”

Again, all calculations are embedded in a user-friendly format linked to the questions in an Excel program (see Appendix3). While the answer in many cases is a judgment call, the relative scores between experiments rarely change unlessthere is a clear and substantial difference between them. It should be noted that the use of countermeasure level as theprimary criterion in the mid term phase hinges on a significant number of countermeasure experiments being in thepipeline by this phase, and the use of CRL (Countermeasure Readiness Levels) instead of the CM scores of Charts A-H.If this is not the case, science score would be substituted as the primary criterion, swapping places with CM.

Results:

Figures 25 and 26 show the results for DSOs and HRF experiments in the mid term phase if the data of ChartsD and H were the actual data 3-6 years from now. The results are based on the science, rather than the CMscore for the reason stated above.

52

Mid Term Score

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1 2 3 4

Science Ranking

Mid Term Score

Score 1

Score 2

636

637499E011635TBDTBD

634

490B

632B504

503S

633

498493500501R639

Figure 25. DSO scores vs science rank

DSOs: The results show that DSOs 635, 636, 637, 499 and E011 should be given the highest priority in theflight manifest, while DSOs 634, 490B, 632B and 504 should receive the next highest priority. All of theseexperiments should be completed as quickly as possible. Conversely DSOs 633, 498, 493, 500 and 501R havescience and performance issues and bear scrutiny for possible de-selection. The others listed in this grouping(DSO 500, and 639) are new experiments that bear scrutiny as they mature. As a point of comparison, Chart1 in Appendix 3 shows how these rankings could be integrated into the kind of red, yellow, green 5x5 sciencematrix that might eventually evolve from the current REMAP guidelines.

53

Mid Term Score

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1 2 3 4

Science Ranking

Mid Term Score

Score 1

Score 2EO96EO83E10

nsbri 009E046

E31

E40 E34E057E120E129

Figure 26. HRF scores vs science priority

HRF: The results show that experiments EO 83, 96 and 104 should be given the highest priority in the flightmanifest, followed by EOs 318, 57 and 400. Conversely, E0s 343, 120 and 129 have science and performanceissues and bear scrutiny. New experiments just in the flight line such as EO57 are not subject to suchassessments but bear scrutiny as they mature.

54

Long Term

The long term phase is designated as 6-10 years but can be shorter or longer as deemed appropriate. For this phase, thegoal is to put a more effective management structure in place capable of optimizing costs and efficiency. This sectionwill address how experiments entering the system would be manifested in this phase (easy to do) and the kind ofmanagement changes needed to optimize cost and efficiency (hard to do).

Manifesting

The manifesting of experiments in the long-term phase must be done differently than in the near or mid term phases, butdoes not depend on whether or not those phases accomplished their goals. In other words, the outcome is temporallyindependent. In this case, Cost Score is the primary criterion and science score, countermeasure value, completion timeand conformance are the secondary criteria.

MTA

The long term phase is designated as 6-10 years but can be shorter or longer as deemed appropriate. For this phase,the goal is to optimize costs with the other parameters serving as tiebreakers. In this regime, the Cost Score for aparticular experiment is:

Long Term Score = fL (Cost), where Cost= fC(Science, CM, Conformance, Comp. Time).

Stated another way, the Long Term score for each experiment will be determined by its Cost data, withCountermeasures, Science, Conformance and Completion Time in that order serving as tiebreakers. As before, thetiebreaker function, in this case, fC, is determined through the Analytic Hierarchy Process (AHP), which usespairwise comparisons to make qualitative and quantitative judgments in a “reasonable” way. In the long term phase,the matrix so derived is:

Key: 1 = A and B are about equal in importance 3 = A is slightly more important than B 5 = A is definitely more important than B 7 = A is strongly more important than B 9 = A is critically more important Note: the reciprocal is used when B is compared to A

Figure 27. AHP Results for the Long Term

sc cm conf cdate

sc 1 1/3 5 7

cm 3 1 3 7

conf 1/5 1/3 1 5

cdate 1/7 1/7 1/5 1

55

Again, the values are subjective, but there is inherent reasonableness to the process in that countermeasure level is themost important parameter when judging cost, followed by science and conformance, which then drives completion time.With the matrix values specified as above, the AHP process can compute relative weights for the science,countermeasure, conformance and completion time scores (w1, w2, w3, w4), which are then used to specify fC from:

fC (Science, Completion Date, Conformance, Countermeasure)= w1* S + w2 * CD + w3 x Conf + w4 * CM 0< fC <1

With fC specified, the Long Term Score can be determined for each experiment in the long term phase.

The computation proceeds as before:

In step a, the scoring envelope is found from the variable, theta, which defines the upper and lower bounds of thescoring function from the user’s answer to simple comparative questions (see below). In Step (b), weights from the AHPmatrix are applied to each experiment’s normalized secondary criterion scores and used to find an interpolation factor rthat determines how close to the upper and lower bounds of the envelope the experiment’s score actually is.Mathematically, the score is expressed as:

Long Term Score= e-(theta*cost)

where cost is the cost score for an experiment from Charts D and H and theta= )1( rr -+q q. As before, the

interpolation factor, r, reflects the overall worth of the secondary criteria in the long-term, in this case, countermeasurelevel, science score, conformance and completion time, with r = 1 reflecting the most favorable and r = 0 the least

favorable set of secondary outcomes. To obtain the values of q and q above, the user is instructed to answer long-termoriented questions such as,

“If an experiment has a perfect long term score of 100 and costs $100K with peak values of science, conformance,countermeasure and completion time, how much more would it cost for its score to be half as much (50)?

While the answer in many cases is a judgment call as before, the relative scores between experiments rarely changeunless there is a clear and substantial difference between them. Again, all calculations are embedded in a user-friendlyformat linked to the questions in an Excel program (see Appendix 3).

Results:

Figures 27 and 28 show the results for DSOs and HRF experiments in the long term phase if the data ofCharts D and H were the actual data 6-10 years from now.

56

Far Term

0.0

0.2

0.4

0.6

0.8

1.0

1.2

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.45

Cost

Score 1

Score 2

Far Term Score

637

E011

501R

633

499

490B

632B

503S

493498

635

634

636

500

639

TBD

504TBD

57

Figure 27. DSO scores vs cost rank

DSOs: The results show that DSOs 499, 503S, 633, 637 and E011 should be given the highest priority in theflight manifest, while DSOs 490B, 632B and 635 should receive the next highest priority. All of theseexperiments should be completed as quickly as possible. Conversely DSOs 493, 498 and 634 have cost,performance or conformance issues and bear scrutiny. The others listed in this grouping (DSO 500, and 639)are new experiments that also bear scrutiny as they mature.

58

Far Term

0.0

0.2

0.4

0.6

0.8

1.0

1.2

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.45 0.5 0.55 0.6

Cost

Score 1

Score 2

Far Term ScoreE104

E343

EO57

E318 nsbri 009

E129

EO83

E120EO96

EO46

E400

Figure 28. HRF scores vs cost rank

HRF: The results show that experiments EO 57, 318 and 343 should be given the highest priority in the flightmanifest, followed by EOs 83, 120 and 129. Conversely, Eos 096 and 400 have cost, performance andconformance issues and bear scrutiny. New experiments just in the flight line such as EO 046 are not subjectto such assessments but bear scrutiny in the future. It should be noted that relative scores and placement ofindividual experiments vary depending on phase, as stated at the outset, and a favorable analysis in the longterm phase could be a poor performer in the short term. It should also be reiterated that this far term analysiscould indeed be used in the near term if cost rather than completion time turns out to be a more criticalparadigm in the near future.

59

MANAGEMENT

Conceiving and implementing management changes six to ten years from now is like looking in a crystal ball. Havingsaid that, certain trends have been noted throughout this document and bear repeating. Ignoring for the moment thatprogram priorities could totally change, the far term approach of cost scrutiny should still be appropriate. The emphasisthen must be on efficiency and effectiveness across the board. This includes:

• An Experiment Commonality Board to insure manifesting of experiments utilizing common parameters andcommon hardware on the same missions

• A Data-sharing board with research science and crew presence to oversee data-sharing issues and prove whydata shouldn’t be shared, not why it should.

• An evidence-based space medicine office to strike a compromise between the current CPR and actual flightobservations

• A reorganization that places the astronaut as a subsystem in the flight science program rather than as thelynchpin of it. This new organization would insure high conformance rates and emphasize cross-disciplinaryphysiological alterations within the context of operational implications. Postlflight egress problems followinglong-duration microgravity exposure is a good example, implicating the sensorimotor, cardiovascular andmuscular systems. A multi-disciplinary team could address the various components underlying egresscapability in a more integrated fashion than currently exists. The concept would carry over to all otheroperational issues such as landing performance, EVA etc. This operational team approach would focus theresearch questions and foster inter-disciplinary interaction. Integrated countermeasures that address changes inmultiple physiological systems can only evolve through such interactions.

• Implementing the 5x5 charts in Appendix 1 to better determine science and countermeasure value for eachexperiment.

• Other changes as noted to Med-Ops, R+0, the Russian Relationship and Payloads

In summary, the ping-pong management style that exists at the present time is unacceptable. The focus for the long termshould be fundamental management change and these changes should begin at once. Such changes will not be easy. Onthe investigators’ side, they may require PIs to assemble in a team approach; sacrifice benefits to their home institution;sacrifice some intellectual property; share data, publications, and so on. Space and Life Sciences has an equal dilemma.How can an organization that has doled out so many dollars to so many contractors and academic institutions for so longhope to combine them in an efficient way? The answer may come from the Operations side of the house. United SpaceAlliance is the sole primary manager for Shuttle operations today, as opposed to the multiple contractors of the past, andISS is still airborne. In the wake of STS-107, however, the jury is still out.

60

CONCLUSIONS

An attempt has been made to list the shortcomings of the current human life sciences flight research program for ISSand Shuttle, with recommendations to mitigate these shortcomings. The approach divided the recommendations intonear, mid and far term solutions, ranging from the specific and pragmatic MTA approach (easy to do) to morepainful and complex management overhauls (hard to do). The dire consequences of ignoring the problems describedin this report cannot be understated. One has only look as far as well written and accurate May 24 article in theHouston Chronicle to see how precarious the situation is. The human flight research program is supposed to be atthe pinnacle of the International Space Station, yet it is subjugated to constraints that conspire to overwhelm it.NASA’s founding fathers would turn in their proverbial graves at the sight of such a convoluted organization. Has itbecome just another organizational bureaucracy whose sole purpose is to dole out taxpayer dollars to contractors andold boys networks in the hypothetical name of science with “not a lot of substance,” as the article contests? If theanswer is yes, make ISS and Shuttle the centerpoint of some other goal such as a human Mars mission, for which itcould be an operational, not a research oriented test-bed. The issue is clear. Voodoo science is not worth the cost.The limb of the fault tree Life Sciences is perched upon is perilously close to breaking.

61

APPENDIX 1

REMAP Guidelines for a Balanced Program

62

63

64

65

Risk Reduction 5x5 Strategy’s for Exploration Class and Balanced Program Missions

7

Score: 5 X 5Risk # 9Acceleration of Age-Related Osteoporosis

Bioastronautics Top Risks

Risk Reduction Strategy Based onA Stabilize & Treat Medical Model

(Long Duration Exploration Class Missions)

CONSEQUENCES

Score: 5 X 5Risk # 31 Propensity to Develop Muscle Injury, Connective TissueDysfunction and Bone Fractures Due to Deficiencies in Motor Skill, Muscle Strength and Muscle Fatigue

Score: 5 X 5

Risk Number: 33Distorientation & Inability to Perform Landing, Egress,Or Other Physical Tasks, Especially During/After G-levelChanges

LIK

EL

IHO

OD

2

5

4

3

1

1 2 3 4 5

25

20

47, 49 15

3014*, 17, 24, 46

9, 31, 33,38, 39, 40

19, 23,29, 34, 36

(7 & 53)28, 37

5

4, 626, 45

11, 18, 22 (27 & 50), 32, 42, 48, 54, 55

3, 8, 10, 23, 41

(1 & 51),(2 & 52)

12, 13, 16, 43, 44

21

CHECS, Habitability & Other ISS Operational Programs

Score: 5 X 5Risk Number: 39Damage to Central Nervous System from Radiation Exposure

Score: 5 X 5Risk Number: 40Synergistic Effects from Exposure to Radiation, Microgravity and Other Spacecraft Environmental Factors

Score: 5 X 5Risk # 38Carcinogenesis Caused by Radiation

35

•Bold Underline = Risk Mitigation Status: no risk mitigation available & substantial research needed

Crew Health, Safety & Performance Requirements

Focused Research (Critical Questions)

66

8

Bioastronautics Top Risks

CONSEQUENCES

LIK

EL

IHO

OD

2

5

4

3

1

1 2 3 4 5

1

Risk Reduction Strategy Based onA Stabilize & Return Medical Model

- ISS 180 (+/- 45 days) Focused Research (Critical Questions)

Crew Health, Safety & Performance Requirements

CHECS, Habitability & Other ISS Operational Programs

(7&53), 9

17, 30,33, 34

38

11

14, 29, 35, 46

18, 19,24, 36,40, 48

49

4, 13, 6, 23, 38, 39, 42, (1&51), 8, 12, 41, 3, 5, (2&52)

25, 28

21, 26, 32,44, 54, 55,20

10, 615, 22,(27&50), 31, 43, 45

Score: 5 X 5Risk No: 17Impaired Carediovascular Response to Exercise Stress

Score: 5 X 5Risk No: 30Inability to Sustain Muscle Performance Levels to Meet Demands of Performing Activities of Various Intensities

Score: 5 X 5Risk No: 33Distorientation & Inability to Perform Landing,

Egress, Or Other Physical Tasks, Especially During/After G-level Changes (Acute spontaneous & provoked vertigo, nystagmus, oscillopsia, poor dynamic visual acuity)

Score: 5 X 5Risk No: 34Impaired Neuromuscular Coordination and/or Strength (Gait, ataxia, postural instabilityP

Score: 5 X 5Risk No: 7 & 53Inadequate Nutrition (Malnutrition)

Score: 5 X 5Risk No: 9Acceleration of Age-Related Osteoporosis

67

Definitions for the 5x5 matrix defining risks and consequence various human subsystems

Bone Loss Risk Analysis

LowRisk Value > 90%

LowRisk Value > 0.90 g/cm2

ModerateRisk 90% > Value > 40%

ModerateRisk 0.90 g/cm2 > Value > 0.60 g/cm2

HighRisk Value < 40%

HighRisk Value < 0.60 g/cm2

Likelihood 1 2 3 4 5Probability 0.00001-0.0001 0.0001-0.001 0.001-0.01 0.01-0.1 0.1-1.0

5

4

3

2

Lik

eli

ho

od

1

1 2 3 4 5

Consequences

OperatingRegion

Trochanteric Density(DEXA: %Preflight

Mean)or

OperatingRegion

Trochanteric Density(DEXA: g/cm2)

68

5 X X

4 X

3 X

2 X

Lik

eli

ho

od

1

1 2 3 4 5

Consequences

Consequences 1 2 3 4 5

Crewmember Health(acute)

No More ThanTemporaryDiscomfort

Short-TermIncapacitation or

Impairment

Long-TermIncapacitation or

Impairment

Significant HealthIssue RequiringHospitalization

Death

CrewmemberPerformance

No More ThanMinor Decrements

Short-TermInability to

Perform MissionObjectives

Long-TermInability to

Perform MissionObjectives

Inability toPerform Complex

Mission Objectives(e.g., EVA)

Inability toPerformCriticalMission

Functions(e.g.,

piloting)

Mission/MissionObjectives

No More ThanMinor Losses or

Delays

Limited Loss ofSignificant

Mission Objectives

Considerable Lossof Significant

Mission Objectives

Abort MissionReturn Crew to

Earth

Loss ofCrew and/or

Vehicle

Crewmember Health(chronic/delayed)

Post-flightRehabilitation

Congruent WithMission Design

SignificantlyIncreased Post-

FlightRehabilitation

Reduced Durationof Astronaut

Career

Significant LongTerm Impairment

or ReducedQuality of Life

SignificantPermanentDisability

orSignificantly ReducedLifespan

CES DependentMeasures

Green Green-Yellow Yellow-Red Red Red

69

APPENDIX 2: METRICS FOR THE HRF AND SHUTTLE FLIGHT EXPERIEMENTS, CHARTS A-H

70

Chart A

RANKING OF DSO FLIGHT EXPERIMENTS BY COUNTERMEASURE AND SCIENCE SCORE

DSO # Title P.I Crit. Risk Crit Quest. CM/Mech* CM score**** Priority**

490B PMZ Putcha 45 11.17, 11.18, 11.19M 6 Yellow 1

493 Latent Vir Pierson 22 7.04 M 6 Yellow 2

498 Immune FxnPierson 22 7.03 M 6 Yellow 2

499 OVAR Clement 33 9.05, 9.25 M 6 Red 1

500 Epstien-Barr Barrett 22 7.23 M 6 Yellow 2

501R Cytokine Uchakin 22 7.03, 7.28 M 6 Yellow 2

503S Midodrine Meck 14 3.09 CM 2 Yellow 2

504 Muscle ctrl DeLuca 28 8.06, 8.08 M 6 Yellow 1

632B GI alteratn Putcha 45 11.16 M 6 Yellow 1

633 Renal Whitson 12 2.06 CM 2 Yellow 2

634 Sleep-wakeCzeisler 19 6.06, 6.08 M 6 Red 2

635 Spatial Paloski 33 9.05, 9.25 M 6 Red 1

636 Spin Moore 33, 36 9.01, 9.15, 9.16 CM 2 Red 1, Ye 2

637 Chromosome Obe 38 10.05, 10.09 M 6 Red 1

639 MechanismsMeck 14 3.05, 3.06 M 6 Yellow 2

E011 EVARM Thomson 38 10.06, 10.09 M 6 Red 1

TBD Grav-inert Merfeld 33 9.03., 9.08 M 6 Red 1

TBD Stability Cohen 13, 14 \3.01, 05, 08, 09 M 6 Red 1, Ye 2 Notes:

* Denotes Countermeasure or Mechanistic study** Priority for a Balanced Program (Draft of Remap guidelines)

*** Score out of a possible 6, 1 being highest**** Countermeasures have a higher priority then mechanisms (point value is 2 versus 6).

*****Denotes if experiment was in development for 3 years or longer or met other deselect criteria

71

Chart E

RANKING OF HRF FLIGHT EXPERIMENTS BY COUNTERMEASURE AND SCIENCE SCORE

Expt # Title Prin. Inv. Crit. Risk Crit Question CM/M* CM Priority** Score***score****

E010 Chromosomeobe 38 10.05, 10.09 M 6 red 1 1E011 Evarm thomson 38 10.06,10.09 M 6 red 1 1

EO44 Puff west 44 11.13 M 6 yel 2 4EO49 Swab (1) pierson 8, 225.12, 7.11, 7.13 M 6 yel 2 4

E046 Cardiac bung/levine 13, 14, 153.01, 3.06, 3.18 M 6 red1, yel 2, gr 1EO57 RenalStne whitson 12 2.06 CM 2 yel 2 4

EO79 Vibe rubin 9, 102.14, 2.19, 2.26 CM 2 red 2, yel 2 2EO82 H-reflex watt 34 9.22 M 6 yel 2 4

EO83 Ultrasound dulchowski 43 11.03 M 2 red 1 1EO85 Voila (2) oman 20 6.12 M 6 gr 1 ******** 5

E088 Spac. Cues clement 33 9.05, 9.25 M 6 red 1 1EO96 Interactions kanas 18 6.01, 6.03 M 6 red 1 1

E104 Journals stuster 18 6.01, 6.03 M 6 red 1 1E117 Card Cont hughson 14, 153.05, 3.17 M 6 ye 2, gr 1 4

E120 Mobility bloomberg 34 9.04, 9.22, 9.24 CM****** 6 ye 2 4E129 Ep.-Barr pierson 22 7.23 M 6 yel 2 4

E290 Xenon1 gabrislson 14 3.05 M 6 yel 2 4E318 Foot cavanagh 9, 102.02, 2.25, 2.26 M 6 red 2, yel 2 2

E343 Sub. Bone lang 10 2.01, 2.14 M 6 yel 2 4E370 Grav Cues merfeld 33, 34 9.02, 9.03, 9.09 M 6 red 1, yel 2 1

E400 Biopsy fitts 31 8.07 M 6 yel 1 3SMOs

SMO 006 Midodrine meck 14 3.09 CM 2 yel 2 4SMO 008 Entry Mon meck M 6

SMO 015 Sams ??SMO 016 Ca Met smith 9 2.25 M 6 red 2 2

SMO 017 Starex putcha yel 2 4SMO 018 aRED hagan NON FLITE

NSBRIsnsbri 009 PSE kanas 18 6.01, 6.03 M 6 red 1 1

nsbri 041 Trec schneider 10/17/30/392.07, 3.13, 8.04, 8.08, 12.0101 CM 2 yel 2, yel 2 4nsbri 042 SADA brunner 45 11.16, 11.19 M 6 yel 1 3

Notes:

* Denotes Countermeasure or Mechanistic study. ** Priority for a Balanced Program, from Draft of Remap guidelines. If multiple priorities, only highest considered in score

*** Score out of a possible 6, 1 being highest (does not consider CM score, which is ranked in composite)**** Countermeasures have a higher priority then mechanisms and are given a point value of 2 as opposed to 6.

*****Denotes if experiment ever met deselect criteria which would detract from its score******Mobility is listed as CM in the CPR but is not a CM to microgravity, only to post flt recovery

*******Voila is listed as behavior expt in CPR, with gr 1 priority but it also may qualify as neurovest expt, with a red 1 priority

72

Chart B

RANKING OF DSO FLIGHT EXPERIMENTS BY CONFORMANCE (N/FLITE) AND FINISHING DATE

DSO Name N require Ncomplete Avg. N/ flight (STS# - #) N/flt (est. N to fin. Flts to fin. End date est.*****by sts113 95-107 95-118 112-118 fin. rate) 5/6/5/6 rate 4/4/4/4rate

490B PMZ 24 11 1.83 1.91 2.28 1.9 13 7 06/3Q 06/4Q

493 Latent Vir 60 40 2.67 2.6 2.28 2.5 20 8 06/4Q 07/1Q

498 Immune Fxn 120 84 4.2 4.2 4.4 4.3 36 9 07/1Q 07/2Q

499 OVAR 10 9 1 1 1.5 1.25 1 1 05/1Q 05/1Q

500 Epstien-Barr 62 16 2.67 2.54 2.5 2.5 46 18 08/2Q 09/3Q

501R Cytokine 10 3 1 1 1 1**** 7 7+ ??

503S Midodrine 20 5 0.83 1.2 1.57 1.25 15 12 07/1Q 08/1Q

504 Muscle ctrl 8 0 1 1* 8 8 06/4Q 07/1Q

632B Pharmaco 12 2 0.33 1 1.67 1 10 10 06/4Q 07/3Q

633 Renal 20 0 0 0 0 0.25* 20 20+ 09+ 10+

634 Sleep-wake 100 10 1.25 1.7 2.57 1.75 90 52 09+ 10+1

635 Spatial 10 5 0.5 0.66 0.75 0.7 5 7 06/3Q 06/4Q

636 Spin 10 0 2 1.25*** 10 8 06/3Q 07/3Q

637 Chromosome 10 0 4.66 2* 10 5 06/1Q 06/2Q

639 Mechanisms 16 0 2 1.25** 16 13 07/3Q 08/2Q

E011 EVARM 9 2 2 1* 7 7 06/2Q 06/4Q

TBD Grav (merfeld) 24 0 1.25*** 24 20 08/3Q 10/1Q

TBD Stability (Cohen) 16v 16 0 1.25** 16 13 07/3Q 08/2QNotes :

* limited history estimate ****Russians only, end-date ????** no history, judged similar to midodrine *****quarter/year, assuming start in fy05 using 5/6/5/6 or 4 flts/year

*** no history, judged similar to OVAR

73

Chart F

RANKING OF HRF FLIGHT EXPERIMENTS BY CONFORMANCE (N/incr.) AND FINISHING DATE

Expt# Name PI N required N comp(1) N comp projected N/incr. N to fin. Inc(yrs) left. last incr. End date est.******Inc2-Inc7 for Inc 7-13 proj fin rate (inc 8 on) (at 2 inc/yr) est******

E010 Chromosomeobe 10 6 12 over 5 increments 2.4 4 2 (1) 9 04/4QE011 Evarm thomson 9 12 none (expt complete) NA 0 0 done done

EO44 Puff west 6 10 none (expt complete) NA 0 0 done doneEO49 Swab pierson NA NA NA NA NA 3 (1.5) 12 05/2Q

E046 Cardiac bung/levine 12 0 0 (proj start in Incr 14) 1.0** 12 12 (6) 19 09/4QEO57 RenalStne whitson 20 13 13 over 6 increments 2.2 7 4 (2) 11 05/4Q

EO79 Vibe rubin 12 0 0 (proj start in Incr 14) 2* 12 6 (3) 13 06/4QEO82 H-reflex watt 4 8 none (expt complete) NA 0 0 done done

EO83 Ultrasound dulchowski 3 0 0 (proj start in Incr 14) 1* 3 3 (1.5) 16 05/2QEO85 Voila oman 6 \ 2 starting increment 13 1.25*** 4 4(2) 11 05/4Q

E088 Spac. Cues clement 5 0 2 starting increment 13 1.25*** 5 4 (2) 11 05/4QEO96 Interactions kanas 15 14 6 over 3 increments 2 1 1 (0.5) 8 04/2Q

E104 Journals stuster 10 0 8 over 4 increments 2**** 10 5 (2.5) 12 06/2QE117 Card Cont hughson 6 0 2 starting increment 13 1** 6 6 (3) 13 06/4Q

E120 Mobility bloomberg 18 9 9 over 4 increments 2.25 9 4 (2) 11 05/4QE129 Ep.-Barr pierson 62 S+L (2) 9L+16S (2) 11 over 5 increments 2.2 37 S+L (2) 9 est L(4.5) 16 08/2Q

E290 Xenon1 gabrislson 4 8 none (expt complete) NA 0 0 done doneE318 Foot cavanagh 3 +3 insur. 1 6 over 5 increments 1.2 5 5 (2.5) 12 06/2Q

E343 Sub. Bone lang 15+ 4 insur. 17 5 over 2 increments 2.5 2 1 (0.5) 8 04/2QE370 Grav Cues merfeld 12 0 2 starting increment 13 1.25*** 12 10 (5) 17 08/4Q

E400 Biopsy fitts 9 +6 insur. 7 10 over 5 increments 2 8 4 (2) 11 05/4QSMOs

SMO 006 Midodrine meck 10 2 10 over 7 increments 1.4 8 6 (3) 13 06/4QSMO 008 Entry Mon meck 8 0 4 over 3 increments 1.4** 8 6 (3) 13 06/4Q

SMO 015 Sams ??SMO 016 Ca Met smith

SMO 017 Starex putchaSMO 018 aRED hagan non flite

NSBRIsnsbri 009 PSE kanas 15 0 6 over 3 increments 2**** 15 8 (4) 15 07/4Q

nsbri 041 Trec schneider 10 0 0 (proj start in Incr 17) 1.2***** 10 9 (4.5) 16 08/2Qnsbri 042 SADA brunner 6 0 6 over 3 increments 2****** 6 3 (1.5) 11 05/2Q

Notes

1. actual subject count through flight completion (does not include post flight R+360 data) 2. S+L means short duration DSO and long duration ISS

* limited history estimate *****no history, judged similar to Foot** no history, judged similar to midodrine ******no history, judged similar to PMZ DSO

*** no history, judged similar to OVAR DSO *******quarter/year, assuming Incr 8 strts 03/4th quarter with****no history, judged similar to Interactions flt rate of 2 inc/yr and same conformance rate pre STS 107 accident

74

Chart C

RANKING OF DSO FLIGHT EXPERIMENTS BY COST TO COMPLETE

DSO Name N required Ncomplete N to fin. est. N/flt Flts to fin. est finish Cost/yr Cost to finish from 05 to complete

by sts113 as of 4/03 (sheet 1) yr, qtr (from SM) flite cost report cost Total

490B PMZ 24 11 13 1.9 7 06/3Q $85K $148.75K 42.5K 191.25K

493 Latent Vir 60 40 20 2.5 8 06/4Q $135K $270K 67.5K $337.5K

498 Immune Fxn 120 84 36 4.3 9 07/1Q $140K $315K 70K $385K

499 OVAR 10 9 1 1.25 1 05/1Q $80K $80K $40K $120K

500 Epstien-Barr 62 16 46 2.5 18 08/2Q $300K $1.05M $150K $1.2M

501R Cytokine 10 3 7 1**** 7+ ?? 0 0 0 0

503S Midodrine 20 5 15 1.25 12 07/1Q $100K $225K $50K $275K

504 Muscle ctrl 8 0 8 1* 8 06/3Q $400K $700K $200K $900K

632B Pharmaco 12 2 10 1 10 06/4Q $85K $170K $42.5K $212.5K

633 Renal 20 0 20 0.25* 20+ 09+ $65K $585K+ $32.5K $617.5K

634 Sleep-wake 100 10 90 1.75 52 09+ $250K $1.25M+ $125K $1.375M

635 Spatial 10 5 5 0.7 7 06/3Q $165K $288.75K $82.5K $371.3K

636 Spin 10 0 10 1.25*** 8 06/3Q $300K $525K $150K $675K

637 Chromoso me 10 0 10 2* 5 06/1Q 0 0 0 0

639 Mechanisms s 16 0 16 1.25** 13 07/2Q $300K $750K $150K $900K

E011 EVARM 9 2 7 1* 7 06/2Q 0 0 0 0

TBD Grav (merfeld eld) 24 0 24 1.25*** 20 08/3Q $480K $3.72M $240K $3.96M

TBD Stability (Cohen) 16ohen) 16 0 16 1.25** 13 07/2Q $350K $875K $175K $1.50M

Notes:

* limited history estimate *****quarter/year, assuming start in fy05 using flt rate of 5/6/5/6 flts/year thru 08

** no history, judged similar to midodrine note: 1 finish date is quarter/year of last flight. Reporting phase followup is 6 months longer.

*** no history, judged similar to OVAR 2. All international experiments have 0 costs (Cytokine, Chrom., EVARM)

****Russians only, end-date ????

75

Chart G

RANKING OF HRF FLIGHT EXPERIMENTS BY COST TO COMPLETE

Expt # Title Prin. Inv. N required N comp(1) N to fin. N/ incr. Inc(yrs) left.Cost/yr Cost from Inc 8 to end (3)Inc2-Inc7 (inc 8 on) proj fin rate (at 2 inc/yr) (from SM) flite cost report cost Total

E010 Chromosomeobe 10 6 4 2.4 2 (1)E011 Evarm thomson 9 12 0 NA 0

EO44 Puff west 6 10 0 NA 0EO49 Swab (1) pierson NA NA NA NA 3 (1.5)

E046 Cardiac bung/levine 12 0 12 1.0** 12 (6) $450K $2.7M $225K $2.925MEO57 RenalStne whitson 20 13 7 2.2 4 (2) $130K $260K $65K $325K

EO79 Vibe rubin 12 0 12 2* 6 (3)EO82 H-reflex watt 4 8 0 NA 0

EO83 Ultrasound dulchowski 3 0 3 1* 3 (1.5) $350K $525K $175K $700KEO85 Voila (2) oman 6 2 4 1.25*** 4(2)

E088 Spac. Cues clement 5 0 5 1.25*** 4 (2)EO96 Interactions kanas 15 14 1 2 1 (0.5) $450K 225K $225K $450K

E104 Journals stuster 10 0 10 2**** 5 (2.5) $30K $75K $15K $90KE117 Card Cont hughson 6 0 6 1** 6 (3)

E120 Mobility bloomberg 18 9 9 2.25 4 (2) $350K $700K $175K $875KE129 Ep.-Barr pierson 62 S+L (2) 9L+16S (2) 37 S+L (2) 2.2 9 est L(4.5) $310K $1.40M $155K $1.56M

E290 Xenon1 gabrislson 4 8 0 NA 0E318 Foot cavanagh 3 +3 insur. 1 5 1.2 5 (2.5) $175K $438K $87.5K $526K

E343 Sub. Bone lang 15+ 4 insur. 17 2 2.5 1 (0.5) $85K $44.5K $42.5K $87KE370 Grav Cues merfeld 12 0 12 1.25*** 10 (5)

E400 Biopsy fitts 9 +6 insur. 7 8 2 4 (2) $600K $1.2M $300K $1.5MSMOs

SMO 006 Midodrine meck 10 2 8 1.4 6 (3)SMO 008 Entry Mon meck 8 0 8 1.4** 6 (3)

SMO 015 Sams ??SMO 016 Ca Met smith $114K $57K

SMO 017 Starex putchaSMO 018 aRED hagan non flite

NSBRIsnsbri 009 PSE kanas 15 0 15 2**** 8 (4) $300K $1.2M $150K $1.350M

nsbri 041 Trec schneider 10 0 10 1.2***** 9 (4.5)nsbri 042 SADA brunner 6 0 6 2****** 3 (1.5)

Notes:* limited history estimate *****quarter/year, assuming start in fy05 using flt rate of 5/6/5/6 flts/year thru 08

** no history, judged similar to midodrine note: 1 finish date is quarter/year of last flight. Reporting phase followup is 6 months longer.*** no history, judged similar to OVAR 2. all international experiments have 0 costs (Cytokine, Chrom., EVARM)

****Russians only, end-date ???? 3. report costs = flite cost billed for 1/2 year

76

Chart D

COMPOSITE RANK OF DSO FLIGHT EXPERIMENTS BY CATEGORY AND MEAN SCORE

DSO # Title P.I N/ flight Cost/yr Rank Rank by Science* CM rank Rank by end date. (from SM) 0-1 scale lower is better for science and CM raw # ofquarters starting 05/1Q

490B PMZ Putcha 1.9 $85K 0.085 3 6 06/4Q 7

493 Latent Vir Pierson 2.5 $135K 0.135 4 6 07/1Q 8

498 Immune FxnPierson 4.3 $140K 0.14 4 6 07/2Q 9

499 OVAR Clement 1.25 $80K 0.08 1 6 05/1Q 1

500 Epstien-Barr Barrett 2.5 $300K 0.3 4 6 09/3Q 18

501R Cytokine Uchakin 1**** 0 0.001 4 6

503S Midodrine Meck 1.25 $100K 0.1 4 2 08/1Q 12

504 Muscle ctrl DeLuca 1* $400K 0.4 3 6 07/1Q 8

632B GI alteratn Putcha 1 $85K 0.085 3 6 07/3Q 10

633 Renal Whitson 0.25* $65K 0.065 4 2 10+ 20+

634 Sleep-wakeCzeisler 1.75 $250K 0.25 2 6 10+ 20+

635 Spatial Paloski 0.7 $165K 0.165 1 6 06/4Q 7

636 Spin Moore 1.25*** $300K 0.3 1 2 07/3Q 10

637 Chromosome Obe 2* 0 0.001 1 6 06/2Q 5

639 MechanismsMeck 1.25** $300K 0.3 4 6 08/2Q 13

E011 EVARM Thomson 1* 0 0.001 1 6 06/4Q 7

TBD Grav-inert Merfeld 1.25*** $480K 0.48 1 6 10/1Q 20

TBD Stability Cohen 1.25** $350K 0.35 1 6 08/2Q 13

NOTESLOWER NUMBERS ARE BETTER FOR ALL CATEGORIES EXCEPT N/FLIGHT CONFORMANCE RATE

* limited history estimate ****Russians only, end-date ????** no history, judged similar to midodrine *****quarter/year, assuming start in fy05 using 5/6/5/6 or 4 flts/year

*** no history, judged similar to OVARNOTE; INTERNATIONAL EXPTS ARE VERY LOW COST, GIVEN A .001 RANK

77

Chart H

COMPOSITE RANK OF HRF FLIGHT EXPERIMENTS BY CATEGORY AND MEAN SCORE

Expt # Title Prin. Inv. Rank by N/flt avg Rank by Cost Rank by Science* CM rank Rank by end date raw $/ yr- SM) 0-1 scale lower numbers are better inc. needed quarters required

E010 Chromosomeobe 2.4 1 6 2inc(1 year) 4E011 Evarm thomson NA 1 6 0 0

EO44 Puff west NA 4 6 0 0EO49 Swab (1) pierson NA 4 6 3 (1.5) 6

E046 Cardiac bung/levine 1.0** $450K 0.45 1 6 12 (6) 24EO57 RenalStne whitson 2.2 $130K 0.13 4 2 4 (2) 8

EO79 Vibe rubin 2* 2 2 6 (3) 12EO82 H-reflex watt NA 4 6 0 0

EO83 Ultrasound dulchowski 1* $350K 0.35 1 2 3 (1.5) 6EO85 Voila (2) oman 1.25*** 5 6 4(2) 8

E088 Spac. Cues clement 1.25*** 1 6 4 (2)EO96 Interactions kanas 2 $450K 0.45 1 6 1 (0.5) 2

E104 Journals stuster 2**** $30K 0.03 1 6 5 (2.5) 10E117 Card Cont hughson 1** 4 6 6 (3) 12

E120 Mobility bloomberg 2.25 $350K 0.35 4 6 4 (2) 8E129 Ep.-Barr pierson 2.2 $310K 0.31 4 6 9 est L(4.5) 18

E290 Xenon1 gabrislson NA 4 6 0 0E318 Foot cavanagh 1.2 $175K 0.175 2 6 5 (2.5) 10

E343 Sub. Bone lang 2.5 $85K 0.085 4 6 1 (0.5) 2E370 Grav Cues merfeld 1.25*** 1 6 10 (5) 20

E400 Biopsy fitts 2 $600K 0.6 3 6 4 (2) 8SMOs

SMO 006 Midodrine meck 1.4 4 2 6 (3) 12SMO 008 Entry Mon meck 1.4** 6 6 (3) 12

SMO 015 Sams ??SMO 016 Ca Met smith $114K 0.114 2 6

SMO 017 Starex putcha 4SMO 018 aRED hagan

NSBRIsnsbri 009 PSE kanas 2**** $300K 0.3 1 6 8 (4) 16

nsbri 041 Trec schneider 1.2***** 4 2 9 (4.5) 18nsbri 042 SADA brunner 2****** 3 6 3 (1.5) 6

NOTESLOWER NUMBERS ARE BETTER FOR ALL CATEGORIES EXCEPT N/FLIGHT CONFORMANCE RATE

notes: quarters required assumes no stoppage from sts107, start date is from increment 7

78

Appendix 3. MTA Program and Sample Output

79

Near-Term Input/Output Set

Enter Quarters: 20Enter Ratio: 3

KEY:

Science CM Conf Cost Theta 1Science 1 0.333333333 5 7 0.06931

CM 3 1 5 7 Theta 2Conf 0.2 0.2 1 5 0.28904

Max 4 6 5 0.75 Cost 0.1428571 0.142857143 0.2 1DSO # Sci Rank CM Rank Conf Rank Cost R Quarters Score 1 Score 2 Theta Near Term Score

499 1 6 1.25 0.080 0.37654 1 0.93303 0.74898 0.20630 0.81359

637 1 6 2.00 0.001 0.39805 5 0.70711 0.23570 0.20158 0.36499

E011 1 6 1.00 0.001 0.37535 7 0.61557 0.13222 0.20656 0.23552

635 1 6 0.70 0.165 0.35923 7 0.61557 0.13222 0.21011 0.22976

490B 3 6 1.90 0.085 0.18425 7 0.61557 0.13222 0.24855 0.17554

504 3 6 1.00 0.400 0.14594 8 0.57435 0.09903 0.25697 0.12800

493 4 6 2.50 0.135 0.09165 8 0.57435 0.09903 0.26890 0.11635

501R 4 6 1.00 0.001 0.06522 8 0.57435 0.09903 0.27471 0.11106

498 4 6 4.30 0.140 0.13222 9 0.53589 0.07417 0.25999 0.09634

636 1 2 1.25 0.300 0.79110 10 0.50000 0.05556 0.11521 0.31596

632B 3 6 1.00 0.085 0.16383 10 0.50000 0.05556 0.25304 0.07963

503S 4 2 1.25 0.100 0.49233 12 0.43528 0.03117 0.18086 0.11414

TBD 1 6 1.25 0.350 0.36121 13 0.40613 0.02334 0.20967 0.06550

639 4 6 1.25 0.300 0.05392 13 0.40613 0.02334 0.27719 0.02723

500 4 6 2.50 0.300 0.08228 18 0.28717 0.00550 0.27096 0.00762

TBD 1 6 1.25 0.480 0.35383 20 0.25000 0.00309 0.21129 0.01461

634 2 6 1.75 0.250 0.27486 20 0.25000 0.00309 0.22864 0.01033

633 4 2 0.25 0.065 0.47162 20 0.25000 0.00309 0.18541 0.02452

good, enter '2'for the value to be half as much?

If two experiments take 5 quarters to complete, and one has all variables at an optimum and the other has all variables at a minimum, how much better is the optimum experiment than the minimum one? Ex. If one was twice as

If an experiment took 10 quarters to complete and all the other variables were at an optimumhow many more quarters would it have to take

9= A is critically more important

Original Matrix (Near Term)1= A & B are equal in importance3= A is slightly more important than B5= A is definitely more important than B7= A is strongly more important than B

80

Mid-Term Input/Output Set

KEY: B1.5000 Quarters CM Conf Cost WeightsTheta 1 Quarters 1 0.2 0.2 3 0.097800.4000 CM 5 1 5 5 0.58855Theta 2 Conf 5 0.2 1 5 0.256000.1000 Cost 0.33333333 0.2 0.2 1 0.05766

6 5 0.75 20CM Rank Conf Rank Cost Quarters R Score 1 Score 2 Theta Mid Term Score

6 1.25 0.080 1 0.21331 0.47237 1.00000 0.16400 0.57807

6 2.00 0.001 5 0.23719 0.47237 1.00000 0.17117 0.59045

2 1.25 0.300 10 0.62090 0.47237 1.00000 0.28626 0.79814

6 1.00 0.001 7 0.17569 0.47237 1.00000 0.15272 0.55877

6 0.70 0.165 7 0.14773 0.47237 1.00000 0.14433 0.54459 Enter ratio 2.12

6 1.25 0.350 13 0.13078 0.47237 1.00000 0.13925 0.53607

6 1.25 0.480 20 0.08476 0.47237 1.00000 0.12545 0.51323

6 1.75 0.250 20 0.12804 0.40655 0.90481 0.13843 0.46315

6 1.90 0.085 7 0.21532 0.25925 0.67035 0.16461 0.33182

6 1.00 0.400 8 0.13987 0.25925 0.67035 0.14198 0.30514

6 1.00 0.085 10 0.15379 0.25925 0.67035 0.14615 0.30996

6 2.50 0.135 8 0.23704 0.22313 0.60654 0.17112 0.29590 Enter ratio 2.59

6 1.00 0.001 8 0.17055 0.22313 0.60654 0.15118 0.27415

2 1.25 0.100 12 0.62598 0.22313 0.60654 0.28778 0.44243

6 4.30 0.140 9 0.32367 0.22313 0.60654 0.19711 0.32576

6 1.25 0.300 13 0.13462 0.22313 0.60654 0.14040 0.26283

6 2.50 0.300 18 0.17289 0.22313 0.60654 0.15188 0.27490

2 0.25 0.065 20 0.53630 0.22313 0.60654 0.26088 0.40595

0.86686 0.74075 1.34977 0.36003 1.28262 Enter ratio 1.11

7= A is strongly more important than B9= A is critically more important

Original Matrix (Mid Term)1= A & B are equal in importance3= A is sightly more important than B5= A is definitely more important than B

If two experiments both have a science

ranking of 1 and one has all other variables

at an optimum and the other has all other

variables at a minimum, how much better is

the optimum than the minimum? 2X = '2'

If two experiments both have a science

ranking of 3 and one has all other variables

at an optimum and the other has all other

1 and the other has a science score of 2, how

much better is the experiment ranking 1 than the

experiment ranking 2? 2X= '2'

variables at a minimum, how much better is

the optimum than the minimum? 2X = '2'

If two experiments both have all other variables

at an optimum, and one has a science score of

81

Far-Term Input/Output Set

Enter Ratio: 3.00KEY:

Science CM Conf Quarters Theta 2 WeightsScience 1 0.333333333 5 7 0.33333 0.33013

CM 3 1 3 7 Theta 1 0.49621Conf 0.2 0.333333333 1 5 1.00000 0.13109

Max 4 6 5 20 Quarters 0.142857143 0.142857143 0.2 1 0.04257DSO # Sci Rank CM Rank Conf Rank Quarters R Cost Score 1 Score 2 Theta Far Term Score

637 1 6 2.00 5 0.41617 0.001 0.99867 0.33289 0.61078 0.60997

E011 1 6 1.00 7 0.38547 0.001 0.99867 0.33289 0.59031 0.58953

501R 4 6 1.00 8 0.05311 0.001 0.99867 0.33289 0.36874 0.36825

633 4 2 0.25 20 0.40352 0.065 0.91333 0.30444 0.60235 0.55015

499 1 6 1.25 1 0.40547 0.080 0.89333 0.29778 0.60365 0.53926

490B 3 6 1.90 7 0.18898 0.085 0.88667 0.29556 0.45932 0.40727

632B 3 6 1.00 10 0.15867 0.085 0.88667 0.29556 0.43911 0.38934

503S 4 2 1.25 12 0.44767 0.100 0.86667 0.28889 0.63178 0.54754

493 4 6 2.50 8 0.09243 0.135 0.82000 0.27333 0.39496 0.32386

498 4 6 4.30 9 0.13739 0.140 0.81333 0.27111 0.42492 0.34560

635 1 6 0.70 7 0.37761 0.165 0.78000 0.26000 0.58507 0.45635

634 2 6 1.75 20 0.26597 0.250 0.66667 0.22222 0.51064 0.34043

636 1 2 1.25 10 0.78227 0.300 0.60000 0.20000 0.85485 0.51291

639 4 6 1.25 13 0.04846 0.300 0.60000 0.20000 0.36564 0.21938

500 4 6 2.50 18 0.07003 0.300 0.60000 0.20000 0.38002 0.22801

TBD 1 6 1.25 13 0.37858 0.350 0.53333 0.17778 0.58572 0.31238

504 3 6 1.00 8 0.16315 0.400 0.46667 0.15556 0.44210 0.20631

TBD 1 6 1.25 20 0.36290 0.480 0.36000 0.12000 0.57527 0.20710

1.08043 1.00000 0.33333 1.05362 1.05362

3= A is sightly more important than B5= A is definitely more important than B7= A is strongly more important than B9= A is critically more important

If two experiments cost .100 to complete, and one has all variables at an optimum and the other has all variables at a minimum, how much better is the optimum experiment than the minimum one? Ex. If one was twice as good, enter '2'

1= A & B are equal in importance Original Matrix (Far Term)

82

Chart 1. MTA analysis integrated with red, yellow, green 5x5 matrix

Mid Term Score

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1 2 3 4

Science Ranking

Mid Term Score

Score 1

Score 2

636

637499E011635TBDTBD

634

490B

632B504

503S

633

498493500501R639

83

program code

define fex4version 7.0/* evaluates mid-term FEX III score function V(q,s,c,m) */args V wcm wq wcf wm s S c C q Q f F m M/* s = science ranking (1 to S) c = countermeasure relevance (1 to C) q = expected # of quarters to complete (1 to Q) f = conformance other than affecting completion date (1 to F) m = cost ranking (1 to M) wcm, wq, wcf and wm are AHP weights for linear comb of c q f mwcm, wq, wcf, wm, S, C, Q, F and M are numerical valuess,c,q,f,m are names of Stata variables where the experiments are theobservations*/

tempvar v1 v2qui gen int `v1'=int((`s'+1)/2)qui gen int `v2'=1+mod((`s'-1),2)qui cap gen y=.qui replace y=117.5-2.5*`v1'*`v1'+1.25*`v2'-16.25*`s'/* generate snew = nonlinear transform of `s' keeping 1 to `S' range */qui cap gen snew=.qui replace snew=1+(1-y/100)*(`S'-1)qui cap gen fs = 0qui replace fs =(`S'-snew)/(`S'-1)

qui cap gen r=.qui replace r =`wcm'*(`C'-`c')/(`C'-1)+`wq'*(`Q'-`q')/(`Q'-1)+`wm'*(1-`m'/`M')+`wcf'*(`F'-`f')/(`F'-1)qui cap gen `V'=.qui replace `V'=fs*sqrt(r)

end

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DSO NEAR TERM 6/5/03

. use fex_dso_050803.dta,clear

. fex3 S_near 0.1733 0.0578 .170 .20 .538 .092 quarters science 4 cmrank 6compliance 4 cnorm 6. gsort -S_near

. list dso quarters r S_near

dso quarters r S_near 1. 499 1 .7296111 .9148182 2. 637 5 .6052055 .5963105 3. 635 7 .8173833 .5756557 4. E011 7 .7845389 .5605705 5. 636 10 .8615 .4780847 6. 490B 7 .4990722 .445036 7. 504 8 .6202222 .443386 8. 632B 10 .6604722 .3790244 9. 493 8 .3284167 .3385976 10. 503S 12 .7170556 .3376448 11. TBD 13 .6951111 .2984387 12. 633 20 .9008611 .2503211 13. 639 13 .5315 .2334347 14. 498 9 .0049777 .2112896 15. TBD 20 .6785 .1497684 16. 634 20 .5615556 .114314 17. 500 18 .3073333 .0837052 18. 501R . .6145389 .

HRF NEAR TERM 5/5/03

. use fex_hrf_050803.dta,clear

. fex3 S_near 0.1733 0.0578 .170 .20 .538 .092 q sci 4 cmrank 6 comp 4 cnorm6. list hrf q r S_near

hrf q r S_near 1. EO83 6 .8999444 .6595889 2. EO96 2 .5478333 .8024783 3. E046 24 .7271667 .1172445 4. E104 10 .6015 .3540676 5. nsbri 009 16 .567 .1781759 6. E318 10 .6697722 .3831177 7. EO57 8 .5428556 .4127961 8. E400 8 .4153333 .3669125 9. E343 2 .3348055 .7639447 10. E120 8 .3457778 .344073 11. E129 18 .3598556 .093363 12. SMO 016 . . .

85

MID TERM DSOs

. use fex_hrf_050803.dta,clear

. fex4 S 0.40 0.10 1.5 .5885 .0978 .2560 .0577 sci cmrank 6 q 24 comp 4raw_cost 600000. gsort -S

hrf sci r S 1. EO83 1 .8610391 .9283857 2. EO96 1 .3219145 .6350873 3. E046 1 .3137 .6307145 4. E104 1 .2878971 .6170384 5. nsbri 009 1 .262384 .6036098 6. E318 2 .3561637 .5725008 7. EO57 4 .7501348 .4950943 8. E400 3 .2964014 .3619382 9. E343 4 .2792478 .310232 10. E120 4 .2750681 .3087941 11. E129 4 .236813 .2958201 12. SMO 016 2 . .

MID TERM HRF

. use fex_dso_050803.dta,clear

. fex4 S 0.40 0.10 1.5 .5885 .0978 .2560 .0577 science cmrank 6 quarters 20compliance 4 raw_cost 600000

. gsort -S

dso science r S 1. 636 1 .8146403 .9036896 2. 635 1 .4062158 .6804254 3. 499 1 .3901667 .6717353 4. E011 1 .3806158 .6665758 5. TBD 1 .3283982 .638545 6. 637 1 .3055772 .6263993 7. TBD 1 .2923666 .6194007 8. 633 4 .8485 .5382872 9. 634 2 .2497 .5202725 10. 503S 4 .8043456 .5187616 11. 504 3 .3754684 .3927107 12. 632B 3 .3651737 .3886292 13. 490B 3 .3038158 .3647668 14. 639 4 .3283982 .3274357 15. 493 4 .2474684 .2994001 16. 500 4 .1959947 .2823494 17. 498 4 .088721 .2488098 18. 501R 4 . .

86

Appendix 4. Sample Revised Ground NRA emphasizing Countermeasures (changes to 2001 NRA in blue)

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March XX, 2003NRA 03-OBPR-XX

OMB Approval No. XXXX

National Aeronautics and Space AdministrationOffice of Biological and Physical ResearchWashington, DC 20546-0001

Research Announcement

Research Opportunities forFlight Experiments in

Space Life Sciencesand Space Sciences

Notices of Intent Due: March XX, 2003Proposals Due: May XX, 2003

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NOTE: THIS IS SECTION 3, for BR&C, changes to 01 NRA are in blue

III. Biomedical Research and Countermeasures and Human Factors Research Emphases

This solicitation requests flight research proposals that will lead to the development of effectivecountermeasures or operational techniques for problems associated with the 12 disciplines covered by theCritical Path Roadmap (see below). These include the following: 1. Cardiovascular; 2. Neurovestibular; 3.Bone; 4. Muscle; 5. Pharmacokinetics; 6. Immune System; 7. Behavior and Performance; 8. Food andNutrition; 9. Radiation; 10 Toxic Exposure; 11. Multisystem and 12. Clinical/Operational Research. NASAand the National Space Biomedical Research Institute have developed the Critical Path Roadmap to guideits bioastronautics research in systematically mitigating or eliminating the risks to astronaut health, safety,and performance during and after space flight. There are 55 risks associated with the 12 disciplinescovered by the Critical Path Roadmap, and 250 unique critical questions whose answers are consideredessential to mitigate the 55 risks. The current flight research program has some 45 experiments either inflight or soon to be in flight. They break down by discipline as follows: Cardiovascular, 7; Neurovestibular,6; Bone, 7; Muscle, 4; Pharmacokinetics, 4; Immune systems, 4; Behavior and Performance, 5; Food andNutrition, 1; Radiation, 3; Toxic Exposure, 1; Multisystem, 1 and Clinical Operation Research, 1. Sincethese experiments constituted the initial complement for long and short duration missions, they wereprimarily mechanistic in nature. Some 84% of the current ISS and STS complement seek to understandmechanisms while 14% propose countermeasures. To achieve its goals of risk mitigation, NASA and theNational Space Biomedical Research Institute will require a far greater complement of countermeasure-based experiments in the future. To implement that requirement, the number of mechanistically-basedproposals accepted in response to this solicitation will be limited to roughly 50% with the remaindertargeting specific countermeasures. The number of experiments selected within each discipline will also belimited according to gaps in the risks not being addressed as well as programmatic concerns. To avoidredundancy with the current flight program and achieve the goals of the CPR, an effort will be made toconcentrate the resources of the flight program on those critical risks not currently being studied or notaddressed by countermeasures. For informational purposes, the distribution of critical risks currentlyaddressed and the number of studies addressing them (in parentheses) are as follows: Cardiovascular, Risk#s 13 (3), 14 (3) and 17 (1); Neurovestibular, Risk #s 33 (4) and 34 (3); Bone, Risk #s 9 (2), 10 (3) and 12(2); Muscle, Risk #s 28 (1), 29 (1) and 30 (2); Pharmacokinetics, Critical Risk #s 45 (3); Immune systems,Risk #s 22 (4); Behavior and Performance, Risk #s 18 (3), 19 (1) and 20 (1); Food and Nutrition, Risk # 8(1); Radiation, Risk #s 38 (1); Toxic Exposure, Risk # 44 (1); Multisystem, Risk # 49 (1) and ClinicalOperation Research, Risk # 43 (1). Submissions addressing the above risks that are mechanistic in naturewithout a proposed countermeasure or a clearly stated description of one evolving from the study will berejected out of hand. In addition to the emphasis on critical risks and countermeasures, programmaticconcerns will also be used to select and prioritize experiments. The ranking of acceptable and selectedflight experiments will be red (high), yellow (medium) or green (low) according to guidelines establishedby the NASA REMAP committee (show 5x5 in Appendix XXX). For comparative purposes, the currentflight program breaks down as follows: Red (highest prioirty)--Critical Risk #s 13, 33, 9, 18, 19, 38 and 43;Yellow (intermediate priority)--Critical Risk #s 14, 16, 17, 34, 10, 12, 28, 29, 30, 45, 49, 22, 44 and 8; andGreen-- Critical Risk # 20. The distribution is roughly 40 % red; 55% yellow and 5% green and of these,only #s 14, 17, 33, 34, 10 and 12 have countermeasures proposed in the suite of existing experiments. Riskscurrently not being addressed at all either mechanistically or with countermeasures for the Bioastronauticsprogram include Risk #s 23, 39, 40 and 46 (High priority Red); Risk #s 11, 21, 7, 53, 55, 31, 36, 41, 42, 24,35, 47, 48, 54 and 49 (intermediate priority Yellow; and Risk #s 3, 4, 25, 32, 37, 15, 26, 27 and 50 (Lowpriority green. It should be added that this distribution is for the current “balanced program” emphasis. Theprioritization of Critical Risks is a dynamic task, as is the Critical Path Roadmap itself. Program shifts suchas a greater emphasis on exploration class missions are likely to change this prioritization and respondeesare cautioned to stay abreast of such shifts.

Once an investigation is selected for flight, the selected investigator will become a member of a researchteam pursuing an integrated set of objectives. While an invitation to participate on a team will be based onthe strengths of the individual proposal, successful applicants will be required to work with other team

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members to develop an integrated set of objectives that can be met within fiscal and flight resourceconstraints. Development of this integrated approach may result in modification, transfer, or deletion ofsome objectives put forth in an individual proposal. A majority of the ISS resources (crew time, launch andreturn logistics, etc.) available for biomedical research will be provided by NASA.

Proposals must clearly and directly benefit the health and/or performance of astronauts during or afterspace flight, and should also benefit people on Earth. Benefits of the proposed research may take any ofthe following forms:• risk assessment, reduction and/or acceptability (monitoring and/or modeling);• scientific knowledge related to the development of appropriate countermeasures or operational

procedures (mechanisms and/or processes);• development of risk mitigating requirements (pharmacological, nutritional/dietary, exercise regimes

and fitness levels, rehabilitation, and/or stress reduction strategies);• development of procedures for medical intervention (diagnosis and treatment, and/or post-landing

rehabilitation);• development of improved procedures for crew screening and enhancing crew selection criteria

(physiological, genetic and psychological criteria, applicable to the individual and/or the group);• improvement of crew training procedures (pre-, in- and postflight, including the use of expert systems);• enhancement of design specifications (related to environmental habitability, including lighting and

noise levels, hygiene, food systems, etc., and the use of artificial gravity and/or mechanical assistancedevices) and improvement of mission operations (monitoring of physiological, behavioral andenvironmental aspects); and

• technology development which will aid in carrying out the research objectives of this solicitation.

A. Primary Research Thrust: Cross-Disciplinary Interactions

Although mechanistic studies are essential to understanding the underlying physiologicalprocesses associated with spaceflight, no system is an island in the human body. Experience hasshown that interactions between physiological systems may dominate overall response and thissolicitation seeks studies focusing on these cross-disciplinary interactions. Proposals that includea plan to account for the interactions of diet, exercise, pharmacologic, neurovestibular,cardiovascular and the other disciplines are actively solicited. Proposals that are highly likely tolead to verifiable countermeasures within three to five years or enhance the efficiency andeffectiveness or current countermeasures such as treadmill exercise are also highly encouraged.

Of particular interest are research proposals that:• use accessible, functional measurements of endpoints (e.g., bone density, muscle size, and strength);• test appropriate pharmacological or hormonal replacement countermeasures, including anti-resorptive

bone agents, growth hormone, and/or sex hormone replacement therapy; (Note: the use of drugsrequires convincing data that they can be safely administered in the space flight environment.)

• account for nutritional requirements and dietary factors;• provide evidence that other indices of muscle function (e.g., surface electromyography) correlate to the

forces generated by specific muscle groups during exercise;• study the use of resistance exercise hardware to prevent loss in muscle strength and mass. Such

research could compare the effectiveness of different exercise prescriptions (e.g., through crew

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exercise time, intensity, duration, frequency, etc.) or could assess the amount of work that is actuallybeing performed. In the event that design, performance, and instrumentation requirements forresistance exercise hardware exceed those of the available hardware (the “Interim Resistive ExerciseDevice” which is described in the Flight Experiment Information Package), the requirements should beclearly specified so that NASA could consider the development of a new device to support highlymeritorious proposals.

• include studies that can lead to new rehabilitation strategies for enhancing and monitoring the recoveryof the musculoskeletal system following space flight.

B. Primary Research Thrust: Human Factors and Behavior & Performance

A second primary research emphasis is to develop or improve preflight or inflightcountermeasures or postflight rehabilitation techniques that will result in measurable improvementin the areas of human factors, psychosocial adaptation, human system design, and humanperformance optimization. Research proposals that are highly likely to lead to verifiablecountermeasures within three to five years are solicited. Excellent proposals will include a plan toaccount for the impact of the proposed countermeasures on the whole human subject.

Human factors proposals are solicited which:• assess and predict crew performance and efficiency;• evaluate effects of the crew-system interfaces on crew performance;• develop and validate non-intrusive methods of assessing human performance that can be related to

crew efficiency and productivity.

Behavior and performance proposals are solicited which:• are designed to understand changes in individual and team performance, and develop countermeasures

to prevent or ameliorate detrimental effects;• identify behaviors, experiences, personality traits and leadership styles that contribute to successful

crew performance during long-duration space flight and develop and validate methods to identify thesefactors during the crew selection process;

• identify acute and long-term effects of exposure to the space environment (microgravity, isolation,stress) on:ÿ human cognition, sensation, perception, learning, problem-solving, and decision making;ÿ the nervous system and related neurobehavioral mechanisms;ÿ human emotional reactivity, stress responses, mood modulation, and vulnerability to affective

disorders.

C Supplemental Research Objective: Clinical Capability

Research in the supplemental area of clinical capability will utilize spacecraft resources (e.g., crewtime, launch and return logistics) not required for the primary research thrusts. In most cases,studies in this area will be implemented as individual investigator experiments, although teamingof investigations may be requested in some cases. Successful proposals will focus on thedevelopment of medical knowledge and technologies required to maintain human health andperformance in space and on return to Earth. Clinical research proposals to develop tools to dealwith acute medical scenarios in space are encouraged (e.g., musculoskeletal injuries includingsprains, contusions and fractures; wounds, lacerations, and burns; toxic exposures and acuteanaphylaxis including drug reactions). In addition, this area includes research required to addressand answer specific questions about inflight on-orbit management of acute medical problems.The highest priority proposals for clinical capability should address:

• development and validation of diagnostic and treatment technologies, protocols and proceduresnecessary to effectively diagnose, treat, and recover patients from likely acute medical scenarios inspace;

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• the most effective options, protocols and technologies to support patient transport and return to Earthfor definitive medical care;

• mechanisms and changes that occur during space flight or immediately postflight in the therapeuticeffectiveness of representative classes of medications;

• the effects and implications of space-flight alterations in human physiology on the absorption,distribution, metabolism, clearance, excretion, clinical efficacy, side effects and drug interactions forclinically useful medications. The most important classes of drugs are antibiotics and anti-infectiveagents, CNS!medications, such as anti-nausea and sleep, that may affect performance and cognitiveacuity, and medications with narrow therapeutic windows such as cardiovascular agents (e.g., anti-arrhythmic). NOTE: During this phase of the International Space Station it is not expected that it willbe possible to conduct standard timed urine and blood sampling, therefore the proposal of alternativemethodologies is encouraged.

• the most appropriate dosage forms and routes of administration for the most commonly administeredand clinically useful medications administered in space flight; and

• diagnostic and laboratory technologies necessary to manage medication side effects and toxicity duringspace flight.

D. Countermeasure Evaluation and Validation Project

Potential investigators should be aware that NASA has established a separate solicitation andreview process for the final evaluation and validation step for specific countermeasures prior totheir implementation as part of regular medical operations in space. No solicitations have beenissued for this program at this time, but one is planned for release later in 2001. Any proposalssubmitted in response to the present solicitation which appear to focus on the final evaluation andvalidation of a specific countermeasure may be held and evaluated later through the reviewprocess established for the Countermeasure Evaluation and Validation Program. Access to thefuture solicitation for this program can be found by following the “research opportunities” link atthe following Web address: http://spaceresearch.nasa.gov.

IV. Flight Experiment Opportunities and Constraints

Two types of flight experiments are currently solicited: (1) pre-mission and post-mission studies involvingdata collection and analysis of biological specimens prior to and on return from space, and (2) on-orbitexperiments that can be implemented on the space platforms of the Space Shuttle or the ISS. Proposalsmust be compatible with the operational constraints and capabilities of the International Space Station andthe Space Shuttle. The Space Life Sciences and Space Sciences Flight Experiments Information Packageprovides detailed information on these constraints as well as a description of the unique aspects of theevaluation and selection process for flight experiments.

All flight experiments must address one or more of the research program emphases defined in Sections IIand III above. Flight investigations must represent mature studies strongly anchored in previous ground-based research or previous flight research. Ground-based research may, and usually must, represent onecomponent of a flight experiment proposal. However, that research should be limited to activities that areessential to the final development of an experiment for flight and for the completion and publication of thescientific results of the experiment. Preparatory ground research designed to define a mature space flightexperiment should be proposed separately and in its own right as part of the ground-based program.

Opportunities for flight experiments are highly competitive due to limited resources. A majority of the capacity ofthe Space Shuttle fleet will be dedicated to assembly and operation of the ISS for the foreseeable future, whichwill limit the opportunities for Shuttle-based experiments (DSOs). ISS experiments will be constrained as welldue to limitations on mass, volume, power, re-supply of consumables, and crew time. In addition, the imposedlimit of a 3 versus 6 person crew for the foreseeable future will also constrain the number of subjects available per

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study. That said, studies requiring an N less than 10 or more than 20 are discouraged. At 2 subjects per missionaverage, this translates to roughly 5-10 missions or 3-6 years per experiment excluding the definition andreporting phase (see below). This is a minimum estimate as actual durations are likely to be longer due to launchdelays, subject non-conformance and other factors.

Priority for initial use of some research hardware on the ISS will be for validation testing of the hardwareoperation and capabilities. Detailed limitations on Space Shuttle and ISS flight experiments are included inthe Space Life Sciences and Space Sciences Flight Experiments Information Package. Proposals requiringresources beyond the capabilities defined in this document should not be submitted in response to thisAnnouncement.Flight experiments that are selected as a result of this Announcement will enter a definition phase. Theexperiment will not be considered for an actual flight prior to successful completion of the definition phase.Selection of a flight experiment through this Announcement does not represent a guarantee for flight.

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Appendix 5. The Experiment Commonality Matrix

94

Experiment Commonality Matrix: Boiler PlateGroundrules:

REMAP..only 3 category red experiments deemed feasible per discipline over ISS lifetimeParts of experiments may be retained /other parts rejectedThose hypothesis with higher score in 5x5 matrix or higher critical question are more essentialParts of different experiments can be combined via datasharingCrew time, implementation complexity and cost are secondary to science relevance at first cutCrew time, implementation complexity and cost determine priority after 5x5 status determined

Science Commonalities

Experiment 1 2 3 4 5 6 7

Hypothesis(key words) Discipline

CPR Question

Priority category (red/yellow/green)

Mechanistic (M) vs Countermeasure (C)

Cost (total)

Subjects required,

Estimated end date

Short/long duration

Increments/STS flts required

Crew time Scale(1-5, 5 being most)

Implementation Scale(1-5, 5 being hardest)

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2. BDC/Data Commonalities (I=inflite, Pr=preflite, Ps=postflite)

Experiment: Expt 1 Expt 2 Expt 3 Expt 4 Expt 5(Russian) Expt 6(ESA)

Parameters measured

Cardiac Output

Cardiac size

Stroke Volume

Compliance

Peripheral Resistance

Blood pressure

ECG

Heart rate

Lung volume

PC02

Bone loss

Others

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3.0 Hardware Commonalities (I=inflite, Pr=preflite, Ps=postflite)

Experiments Expt 1 Expt 2 Expt 3 Expt 4 Expt 5 (Russian) Expt 6 (ESA)

MRI

DEXA

EKG

Echo

Doppler

CVP

LBNP

Holter EKG

Echo

Actigraphy

R+0 –specific issues

Exclusion issues

Crew constraint issues

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Experiment Commonality Matrix: (Cardiovascular) Groundrules: REMAP..only 3 category red experiments deemed feasible per discipline over ISS lifetime Parts of experiments may be retained /other parts rejected Those hypothesis with higher score in 5x5 mat rix or higher critical question are more essential Parts of different experiments can be combined via datasharing Crew time, implementation complexity and cost are secondary to science relevance at first cut Crew time, implementation complexity and cost d etermine priority after 5x5 status determined

A. Science Commonalities Experiment Cardiac Atrophy Cardiac Control Bone Cardiac Stability PI Bungo/Levine Hughson Lang Cohen Hypothesis cardiac atrophy artererial baroreflex bone loss hemodynamics (key words) diastolic function ARMA model CSI Model TWA analysis venous compliance TWA analysis , filling dynamics peri resistance, HR HR baroreflex

ECG,.arrhythmia ECG,. arrhythmia ECG,.arrhythmia stroke volume stroke volume stoke volume, hypovolemia vasoconstriction tilt test Ortho. Intolerance Ortho. Intolerance Ortho. Intol. Cardiac output Cardiac output 3 aims: CSI, Q-T disp.elect.cond. ECG, R-R segment TWA, midodrine

Invasive CVP Invasive CVP/LBNP Non invasive In flite ultrasound HR var/beat by beat HR/beat by beat MRI Discipline Cardiovascular Cardiovascular Bone Cardiovascular CPR Risk # 13, 14, 15 14, 15 13/14 Priority category Red 1/Ye2/Gr2 Ye2/Gr 2 Red1/Ye2 Mechan (M)/CM M M M M/ (CM) CPR Question 3.01, 3.06, 3.18 3.05, 3.17 3.01, 3.05,

3.08, 3.09 Cost (total) $3.3M $10-15K (impl. $ only) $1.01M (NSBRI) Subjects required, N 12 6 15 36 Estimated end date 2008 2006 2004 2008 Short/long duration L L L L/S Increment/STS flts 6 2 7 18 STS Crew time flt/grnd* 3.5/3.5 3/3 NA NA/2 Implement. scale* 4 4 1 1

*1-5, 5 being most difficult

98

2. BDC/DATA Commonalities Experiment Bungo/Levine Hughson Lang Cohen (NSBRI) Parameters measured Cardiac Output Cardiac size Stroke Volume Compliance Peripheral Resistance Blood pressure ECG Heart rate Lung volume PC02 Bone loss R-R wave Q-T interval Twave alternans

99

3.0 Hardware Commonalities (I=inflite, Pr=preflite, Ps=postflite) Experiment-- Bungo/Levine Hughson Lang Cohen (NSBRI)

MRI DEXA EKG Echo Doppler CVP LBNP

Holter EKG Echo Actigraphy

R+0 –specific issues

Exclusion issues Crew constraint issues

100

Experiment Consolidation Matrix: Neurovestibular Groundrules:TBD as per REMAP….best guess as follows: 3 category red experiments deemed feasible per discipline over ISS lifetime Parts of experiments may be retained /other parts rejected Those hypothesis with higher score in 5x5 matrix or higher critical question are more essential Parts of different experiments can be combined via datasharing Crew time, implementation complexity and cost are secondary to science relevance at first cut Crew time, implementation complexity and cost determine priority after 5x5 status determined A. Science Commonalities--NEURO Experiments 1. Influence of sens int on grav/inert. cues (E370A/B) 2. Centrifugation as a Countermeasure for Otolith Deconditioning During Spaceflight (DSO#) 3. Effect of Off Vertical Axis Rotation on eye movement&motor perception (OVAR -DSO499) 4. Effect of Altered Gravity on spinal cord excitability (H-Reflex-E082) 5. Sensory Motor Response Generalizibility (Motor—E120) 6. Spatial Orientation (DSO635) PI:s 1 Merfeld 2. Moore 3. Clement 4. Watt 5. Bloomberg 6. Paloski 7.RSA Hypothesis influ. of semi influ of Co-PI with (key words) cir. canals & otolith/ocular Moore vision on tilt reflexes on & translation orthostat. intol. , percept. Effect Control data of null gravity to validate Manual & neurolab Passive tilt . AG data. Protocols Protocols- xntrl input static tilt Eye movement eye move Discipline N E U R O V E S T I B U L A R CPR Question 33 33 33 34 34 33 Priority Red 1 Red 1 Red 1 Yellow 2 Yellow 2 Red 1 Mechanism/CM M CM M M CM M Cost (total) $3.32M $0.57M (impl. $ only) Subjects required 10 10 5 4 18 10 End date (est) Incr 13 2006 Duration (S/L) L/S S S L L S Increments/STS flts 3/3 Crew time Scale (1-5, 5 being most) Implementation Scale

101

Appendix 6. R+0 Principal Investigator Query