Ten Commandments of Successful Trial Management

Ten Commandments of Successful Trial Management1

Susan E. Margitic, M.S.,2 and Nancy L. Miles, M.S.N.

Department of Public Health Sciences, Bowman Gray School of Medicine, Wake Forest University,Winston-Salem, North Carolina 27157-1063; and Department of Preventive Medicine, University of Tennessee,

Memphis, Tennessee 38105-9664

A well-designed, adequately funded clinical trialbased on sound science and conducted by experiencedinvestigators and staff can falter if participating trialclinics are not managed well. Ten commandments forsuccessful trial clinic management address key orga-nizational and operational issues.

● Commandment I: Thou shalt know and follow thyrules.

● Commandment II: Thou shalt know and fulfill thyroles.

● Commandment III: Thou shalt meet thy commit-ments.

● Commandment IV: Thou shalt collaborate.● Commandment V: Thou shalt communicate.● Commandment VI: Thou shalt document.● Commandment VII: Thou shalt honor thy partici-

pants.● Commandment VIII: Thou shalt keep thy partici-

pants’ secrets.● Commandment IX: Thou shalt revere thy data.● Commandment X: Thou shalt know and accept

thy limitations.

This report puts these commandments into contextby providing concrete examples in the clinical trialsetting. These commandments could serve as guide-lines to the spectrum of personnel involved in the op-erations of a trial clinic, namely, principal investiga-tors and co-investigators, trial coordinators, datamanagers, technicians, administrators, and supportstaff. © 1998 Academic Press

Key Words: clinical trial; management; organization;communications; trial management communications.

INTRODUCTION

Clinical trial management issues have not received agreat deal of attention in the clinical trial or medical

literature. Although a triad of key textbooks do offersome discussion on this topic [1–3], few journal reports,to our knowledge, focus on trial management [4–6]. Op-erations and management of a trial clinic may not rep-resent ‘‘rocket science,’’ but lack of their considerationcould contribute to the failure of a well thought out,soundly designed study. Poor management can havetremendous repercussions on recruitment efforts (lead-ing to unexpected study extensions [7] or prematuretrial closure [8]), and can potentially compromise dataquality as well as impede an investigator’s efforts tocompete for future research awards.

In Hunninghake’s article on recruitment in clinicaltrials [9], the ramifications of facing a prolonged re-cruitment period are discussed. These same conse-quences could be cited for a poorly managed trial clinic:‘‘. . . prolonged duration of the trial, increased costs,morale problems for both participants and staff, andpossible alteration of the study results.’’

This report focuses on key management and opera-tional issues with which experienced trial personnelare very likely familiar, but which have not been com-prehensively addressed in the literature. These issues,formulated as ten commandments for successful trialmanagement, could prove useful to those new to clini-cal trials and could perhaps serve as worthwhile re-minders to those already involved in trial clinic opera-tions. Although the information offered is based pri-marily on the multicenter clinical trial experience ofthe authors, these directives are relevant to single-center trial clinics as well.

TEN COMMANDMENTS OF SUCCESSFULTRIAL MANAGEMENT

Commandment I: Thou Shalt Know and Follow Thy Rules

Whether a study is multicenter based or a singleresearch clinic, standardization and consistency areimperative for the collection of highly credible data.Trial staff and study investigators should have a work-ing knowledge of the study protocol and the more de-tailed Manual of Procedures (MOP) that elaborates onprotocol procedures. Local training and certification/

1 Adapted from a lecture given in the Clinical Trials ManagementWorkshop I at Bowman Gray School of Medicine.

2 To whom reprint requests should be addressed at Public HealthSciences, Bowman Gray School of Medicine, Medical Center Boule-vard, Winston-Salem, NC 27157-1063. Fax: (910) 716-5425. E-mail:[email protected].

PREVENTIVE MEDICINE 27, 84–92 (1998)ARTICLE NO. PM970243

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0091-7435/98 $25.00Copyright © 1998 by Academic PressAll rights of reproduction in any form reserved.

recertification for protocol-related procedures help tomaintain the theoretical and practical knowledgeneeded by trial personnel. Procedural revisions instudy conduct (usually originating from the sponsor orstudy coordinating center) should be relayed promptlyto trial personnel so that appropriate changes can beimplemented. Regular contact between the sponsor orcoordinating center and the trial coordinators can fa-cilitate procedural changes and clarify evolving issues.

Trial recruitment can present special challenges interms of complying with study regulations and policies.Temptations to ‘‘bend’’ the eligibility rules must be re-sisted. This can prove especially difficult when recruit-ment is not going well [1]. Clinic personnel must ad-here rigorously to the protocol inclusion/exclusion cri-teria and must also remain keenly aware thatrandomization of a participant into a trial is usuallyconsidered an irreversible process (in terms of partici-pant follow-up and, if appropriate, continued treat-ment). Study staff and investigators need to under-stand and abide by the intention-to-treat principle(once randomized, always analyzed), which, in manyrespects, guides trial conduct during both the recruit-ment and the follow-up phases of a study (in terms ofrandomization, adherence, and retention).

Trial personnel also face conflicts in adhering to theprinciple of trial blinding. Although one can appreciatethe importance of blinding as a strategy to minimize ahost of biases in clinical trials [1], some may perceivethis approach to be a hindrance to honest and opencommunications with participants, which remain a keycomponent to the successful clinician–patient relation-ship. All trial personnel must understand and be will-ing to honor the rules of blinding. Equally important isthe appreciation of and willingness to abide by the con-ditions dictating unblinding (for example, when neededto evaluate and treat severe adverse events).

In addition to knowledge of and adherence to trial-wide rules, regulations, and guidelines, there needs tobe awareness of and compliance with (1) local institu-tional policies [(a) Institutional Review Board (IRB)guidelines such as proper procurement and documen-tation of informed consent and securing IRB approvalfor revisions to the approved protocol or the informedconsent document, (b) Occupational Safety and HealthAdministration regulations, and (c) handling/accountability/disposal of study drugs] and (2) sponsorand government policies [(a) National Institutes ofHealth and (b) Food and Drug Administration (FDA)rules and regulations].

Commandment II: Thou Shalt Know and Fulfill Thy Roles

All clinical trial personnel need to be aware of theirexpected roles, which should be defined clearly duringthe interview or orientation process. Key personnel in-volved in running a trial clinic include clinicians, cliniccoordinators, data collectors, data coordinators, re-

cruitment coordinators, technicians, and support staff,as well as specialized personnel who are unique to theintervention being evaluated (e.g., dietitians involvedin a dietary intervention).

Personnel configuration will vary from site to site,depending, in great part, on available resources. How-ever, two prominent players generally remain as ‘‘con-stants’’ in clinical research studies [5]: the trial coordi-nator and the principal investigator. Their activities,which can influence all aspects of trial conduct andoperations, are discussed below (Tables 1 and 2 sum-marize these roles).

A. Roles of the Trial Coordinator

Sometimes referred to as the clinic coordinator, clinicmanager, program manager, or project manager, therole of the trial coordinator has been described in anumber of reports [10–14]. Trial coordinators may ormay not be clinicians involved in direct participanthealth care; however, all should be considered researchprofessionals who make significant contributions to hu-man research studies [5]. This position involves nu-merous administrative responsibilities, such as coordi-nating IRB documents (consent forms and annual IRBreports), reporting adverse events to the sponsor or tothe study coordinating center, overseeing drug ac-countability, and expediting paperwork for clinic par-ticipants/staff and clinic operations.

Trial coordinators, in some scenarios, may have toassume the role of fiscal specialist, attending to clinicbudgets and interacting with the trial sponsor as wellas the local institution to address fiscal matters thatare critical to continued study operations. Anothercritical role is recruitment coordinator. Even when suf-ficient funds are available to hire other personnel torecruit participants into a study, the trial coordinatorusually oversees recruitment efforts to ensure that tar-get recruitment goals are met on time. The trial coor-dinator also frequently serves as the primary liaison[regularly communicating with the principal investiga-tor (PI), sponsor representatives, trial staff, partici-pants, participants’ families, and physicians], team

TABLE 1General Responsibilities of the Trial Coordinator

• Clinician• Research professional• Administrator• Fiscal specialist• Recruitment coordinator• Liaison• Team leader• Educator• Counselor and confidante• Strategic planner• Arbitrator• Resource person

TEN COMMANDMENTS OF TRIAL MANAGEMENT 85

leader, and clinic educator (coordinating training andcertifying/recertifying staff on protocol-related activi-ties and ensuring staff compliance with national andinstitutional regulations). Clinic education also entailsinstructing participants about intervention and com-pliance issues.

Since the trial coordinator, by definition, coordinatestrial operations, certain responsibilities should be con-sidered mandatory for this position. These would in-clude functioning as a counselor and confidante (to staffand participants), strategic planner (facilitating clinicflow, being sensitive to staff burden, participating inshort- and long-term planning efforts), arbitrator (ad-dressing personnel conflicts, participant adherenceproblems), and primary resource person (who is inti-mately familiar with the study protocol and MOP andwho can advise both staff and participants on trial-related matters). As the primary resource person in theclinic, the trial coordinator should be familiar with allaspects of trial operations, for backup purposes as wellas to be better able to appreciate and advise staff, togain their respect, and to enhance professional cred-ibility.

Trial coordinators need to examine their strengthsand weaknesses in the above-noted roles so that theycan perhaps delegate some of these responsibilities toother colleagues who may have greater expertise inparticular areas. Whether they assume all or some ofthese roles, trial coordinators often face new challengesthat call for creativity and flexibility to find solutionsthat remain within the guidelines of the study protocol.

B. Roles of the Principal Investigator

There is very little in the clinical trial literatureabout the role of the trial investigator [15] or the PI[4,5]. This is unfortunate, because many trial investi-gators have minimal experience in the administrationand management of research trials [16]. Principal in-vestigator responsibilities formulated in this paper arebased on our experience and interaction with a numberof PIs who fulfill all the roles listed below. Some ofthese roles relate to nonmanagement topics, but in of-fering descriptions of these roles, we felt that a morecomprehensive overview would be relevant. These re-sponsibilities relate to the trial itself, to trial partici-pants, to trial personnel, and to the medical commu-nity.

1. PI responsibilities to the trial. The trial PI ideallyhas input into the design of a clinical trial since he orshe should accept substantial responsibility for theconduct and findings of the study. In assuming thisrole, the PI implicitly agrees to provide good manage-ment of the study clinic and effective study leadership.An example of the former includes assuming a proac-tive role during the planning phase of the trial (secur-ing adequate clinic space, making contact with othermedical investigators/facilities to be included in thetrial, etc.). The serious commitment of meeting the clin-ic’s recruitment goal is not to be taken lightly. Prelimi-nary enthusiasm and optimism can wane as the rigorsof recruitment become all too real [17,18]. Failure torecruit participants in a timely fashion could be inter-preted as a lack of commitment to the trial.

Principal investigators also should be willing tovouch for the scientific integrity of the study (includingethical conduct as well as data integrity), should dis-close any potential conflicts of interest (holding stock inor receiving consulting fees from the company produc-ing the drug/device that is being evaluated) [19], andshould participate in the dissemination of study results(active involvement in the preparation of the primaryoutcome paper and other trial-related manuscripts andpresentation of trial findings at scientific meetings).Efforts to maintain the scientific integrity of the studyshould include communicating to all trial investigatorsand staff the reasons for random (and often blinded)allocation of treatment assignments and the impor-tance of ensuring that randomization does indeed re-main a random process [20].

Faculty level clinicians and researchers who are con-sidering the prospect of serving as clinical trial PIs arevery likely more interested in the scientific rather thanthe management aspects of trial participation. This is,in part, a reflection of the premium placed on scientific(as opposed to management) expertise in academia. Asuccessful PI is one who appreciates the intimate rela-tionship between good science and good management.

TABLE 2General Responsibilities of the Principal Investigator

To the trial• Design• Management• Leadership• Meeting recruitment goal• Scientific integrity• Conflicts of interest• Dissemination

To trial participants• Communication• Accessibility• Medical management

To trial personnel• Accountability• Familiarity with clinic operations• Accessibility• Support, direction, and mediation• Delegation with authority

To the medical community• Information about trial• Regular contact with participants’ physicians• Promote team approach

MARGITIC AND MILES86

2. PI responsibilities to participants. Although notall PIs have direct and frequent contact with studyparticipants, PIs should be willing to communicatewith participants when the need arises (perhaps to dis-cuss a safety issue that is of concern to a participant orto facilitate compliance) [21]. Toward this end, the PIshould be accessible to the participant. In accepting therole of principal investigator, the PI should also as-sume responsibility for appropriate medical manage-ment of the participant. (See also No. 4 of this section).

3. PI responsibilities to trial personnel. The PIshould be held accountable for trial clinic conduct andoperations. This accountability should encompass in-vestigator and staff adherence to good clinical practicepolicies and to the study protocol. In multicenter clini-cal trials, management problems at one site can affectthe entire study. In trials that we have been involvedin, the sponsor—and study investigators at othersites—turn to the PI when problems materialize in his/her clinic. Within the context of accountability is theexpectation that the PI will have a working knowledgeof the study protocol as well as familiarity with allaspects of clinic operations.

Several reports [22,23] have confirmed that investi-gator unavailability and lack of involvement in a trialrepresent significant sources of frustration for trial co-ordinators. PI accessibility to study staff is critical.This may entail not only meeting regularly with staff,but being available on an ‘‘as needed’’ basis to providesupport, direction, and, if necessary, mediation. Al-though trial operations in a particular trial clinic mayrepresent just one piece of a PI’s professional pie, trialstaff usually have a much greater time commitment tothe study. PI attentiveness, encouragement, praise,and willingness to advise and troubleshoot demon-strate a commitment to the trial and to the trial staff.Finally, the often frequent removal of PIs from day-to-day clinic operations mandates that the PI delegatewith authority to that person coordinating clinic activ-ity [2]. This could be a study co-investigator or the trialcoordinator.

4. PI responsibilities to the medical community.The medical community should be informed about anupcoming clinical trial that may enroll patients of localphysicians [9,24,25]. The PI should be involved activelyin ‘‘priming’’ the medical community via letters to phy-sicians and presentations to local medical organiza-tions. Community physicians should be informed thatpatient involvement in the trial will not include pri-mary care, but that patient welfare and safety remaina primary concern for those enrolled in the study (seeCommandment V, Section B, for additional safety in-formation to be communicated to study participants’physicians). The PI should ‘‘reach out’’ to physicians of

enrolled (or potentially enrolled) participants [26]through early and regular contact to enlist their coop-eration and support. This, in turn, can promote a teamapproach between trial staff and the personal physi-cian that may facilitate participant trial compliance.

The authors of this report acknowledge that the rolesdescribed above are not all inclusive and will, espe-cially for the trial coordinator, vary with the type oftrial, the available funding, the personnel configura-tion of the trial clinic, and the individual expertise ofthose assuming these roles.

Commandment III: Thou Shalt Meet Thy Commitments

Being part of a trial clinic implies making certaincommitments, such as agreeing to abide by the studyprotocol, being willing to put forth the enormous effortand extra time to screen and randomize a predeter-mined number of participants, fulfilling assigned trialroles, and working as a team to accomplish mutualgoals. During the interviewing process, prospectivetrial employees should be made aware of the responsi-bilities they will assume and the corresponding com-mitments expected of them. These should be discussedin the context of the environment in which they will beworking. The implications of working in a trial clinic asopposed to a regular clinical practice should be con-veyed, since the activities and goals of these two dif-ferent work settings vary considerably [12]. For ex-ample, trial clinic patient management focuses on pro-tocol-related outcomes and adverse events, with moregeneral patient care being channeled back to the pri-mary physician. Clinicians working in a study clinicmust also be willing to accept more rigorous training,more routine quality control monitoring, and less flex-ibility in practicing medicine than if they were workingin a regular medical practice.

Often, the goals and commitments of a study changeas the study evolves. New tests/procedures may be re-quired without the benefit of additional funding or un-expected budget cuts may be encountered. This callsfor exercising flexibility and finding creative solutionsto meet new commitments (enlisting services of volun-teers, obtaining contributions in goods and servicesfrom local businesses, etc.).

Commandment IV: Thou Shalt Collaborate

Although managing a trial clinic involves division oflabor, successful trial operations depend on group andindividual efforts. No one person can conduct even thesmallest trial single-handedly. Collaboration, thereforeis a primary factor in successful trial clinic operations.

Collaborative activities involved in running a trialclinic include:

● trial coordination (managing and coordinatingclinic activities),


● recruitment coordination (committed to screeningand recruitment),

● retention/adherence monitoring (committed toparticipant retention in the trial and adherence tothe assigned treatment regimen),

● data collection (interviewing participants andcompleting the data collection forms),

● data coordination (editing the forms, keying thecollected data into the study database, correctingdata errors),

● clinician responsibilities (performing physical ex-ams and medical tests, interpreting diagnosticprocedures),

● technician responsibilities (drawing and process-ing blood, performing blood pressure and othermeasurements),

● outcomes surveillance (verifying primary and sec-ondary study endpoints), and

● support staff responsibilities (preparing writtendocuments, providing phone support, schedulingappointments, etc.).

Unfortunately, we live in a fiscal climate dictated bybudget constraints [27] and controlled staffing pat-terns, compelling investigators to make difficult deci-sions concerning staff configuration. One solution tothis problem involves hiring individuals to assumemultiple roles: the trial coordinator may be the studyclinician, support staff could be trained to do data en-try, and the recruitment coordinator could later focuson retention/adherence activities.

Investigators need to prioritize staff positions, thendetermine which multiple responsibilities could be as-sumed by one person. Factors affecting these decisionsinclude the level of funding, the size of the trial, thelevel of expertise among trial staff, and the personalpreferences of the PI and the trial coordinator. An im-portant downside to this approach is the greater prob-ability for staff burnout among those individuals whodo perform multiple trial activities. The advantages ofthis tactic relate to cross training (which should beimplemented in all trial clinics to allow for backup ofkey personnel) and greater job satisfaction and com-mitment for those individuals who enjoy the challengeand diversity associated with assuming multiple jobresponsibilities.

Another dimension of trial collaboration relates tocollaboratively written clinical trial reports. Investiga-tors should be aware that nonfaculty study personnelsuch as trial coordinators may be just as eager to par-ticipate in the publication process as their faculty/investigator counterparts. Opportunities should beavailable for key trial employees to become engaged inand receive credit for publication efforts.

Commandment V: Thou Shalt Communicate

Good communication is the cornerstone of collabora-tion. Effective (and reciprocal) communication is one of

the most essential components of multicenter clinicaltrials [16].

Three primary modes of communication in the clini-cal trial setting include communication among clinicalstaff, communicating with participants’ physicians,and clinic communications with the coordinating cen-ter and/or trial sponsor (communications with studyparticipants is discussed under Commandment VII).Table 3 provides a summary of communications in aclinical trial.

A. Communications among Clinical Staff

Regular and frequent staff meetings provide forumsfor discussion of logistical issues such as problems withclinic flow and recruitment and compliance. Thesemeetings also provide opportunities to build staff mo-rale, reinforce team building, and allow staff to airgrievances that may be shared by their colleagues. Tochannel such interactions in a productive direction, theperson conducting these meetings in the absence of thePI needs to have good delegation of authority from thePI. Communication also involves resolving conflictsthat may arise among staff or between staff membersand participants, briefing the PI on appropriate issues,and ensuring that the PI briefs trial staff on policy orprotocol changes. Successful communications with thePI implies PI accessibility to his/her staff.

TABLE 3Communications in the Clinical Trial Setting

Communications among trial staff• Regular and frequent staff meetings• Good delegation of authority• Resolving conflicts• Briefing the PI• PI briefs staff• PI accessibility• Encourage comments from co-workers• Hierarchy of communication

Communications with participants’ physicians• Establish early contact• Provide information• Reassure physicians’ roles as primary caregivers• Forward appropriate and pertinent participant data• Refer participants back to physicians• Promote team approach

Communications with participants• High priority to informed consent• Quick follow-up on inquiries• Timely provision of appropriate clinical data• Good clinic phone coverage• Uniform information from staff and investigators• Convey sincerity, patience, sensitivity, and recognition• Accommodate participant needs• Maintain professional integrity/appearance

Communications with coordinating center or sponsor• Routine issues• Safety issues• Clarification


The clinic supervisor (usually the trial coordinator ora study co-investigator) should encourage commentsand suggestions from co-workers. These can providefresh perspectives that may lead to improved opera-tions, and they demonstrate appreciation for and rec-ognition of trial employees.

Finally, a hierarchy of communication needs to beestablished so that staff members know to whom theyshould report and with whom they could consult aboutparticular issues.

B. Communications with Participants’ Physicians

As noted under Commandment II, Section B4, trialclinic personnel should establish early contact withparticipants’ physicians (usually through a lettersigned by the PI) to inform physicians of their patients’involvement in the trial; to provide information aboutthe trial goals, interventions, risks, benefits, length offollow-up, frequency of follow-up visits, tests, and pro-cedures; and to reassure physicians that they will re-main the primary health care providers for their pa-tients. Also to be communicated to participants’ physi-cians are promises to forward appropriate andpertinent participant data in a timely fashion (routinetest findings, pathology reports, etc.) and to refer par-ticipants back to their physicians should unexpectedfindings emerge in the trial clinic. These communica-tions, though time-consuming for clinic staff, can pro-mote a team approach between the trial clinic and thepersonal physician. Potential participants should beencouraged to discuss trial enrollment with their per-sonal physicians [28]. Continued support for the trialfrom a participant’s health care provider can facilitateparticipant trial compliance.

C. Communications with the Coordinating Centerand/or the Trial Sponsor

Communications with the coordinating center and/orthe trial sponsor could be classified into three catego-ries: routine, safety related, and clarification. Ex-amples of routine communications include regularlyscheduled conference calls [16] (during which informa-tion is shared between sites and protocol issues andproblems are discussed), clinic requests for central pur-chase of standard inventory items (blood collection sup-plies) or unexpected additional items not included inthe original clinic budget, and discussions regardingdata edits/corrections and budgetary issues. Examplesof safety-related communications include reporting ad-verse events, questioning whether or not a study medi-cation should be discontinued or tapered, requestingan emergency unblinding of a participant, and provid-ing information regarding the death of a study subject.Clarification issues often refer to interpretation of theprotocol, questions about study eligibility, administra-

tion of the intervention, exceeding the permitted windowof time surrounding a screening or follow-up visit, etc.

Commandment VI: Thou Shalt Document

Proper study documentation involves accuratecompletion of the data collection forms in conjunctionwith interviewing participants and retaining data-related source documents (lab slips, pathology or ECGreports, etc.). Examples of critical documents to bestored and updated on site include IRB approval lettersand communications, protocol amendments and MOPrevisions, FDA 1572 Forms for investigational drug tri-als (to be completed for original and new investigatorsjoining the study), and investigational drug adverseevent reports and accountability logs. Important writ-ten and e-mail communications should also be stored,and pertinent phone calls should be documented andfiled. These could relate to protocol interpretation (forexample, confirmation from the coordinating centerthat a participant remains eligible for enrollment de-spite some unusual circumstance or condition), report-ing adverse events to the FDA/coordinating center/sponsor, and relevant conversations with participants,their physicians, or study sponsor representatives.

Commandment VII: Thou Shalt Honor Thy Participants

Without participants, there would be no clinical re-search. Respect, concern, and appreciation should beconveyed to all potential and randomized participants,in conjunction with providing comprehensive yet un-derstandable information about the trial. Informationgiving begins during the informed consent process. De-spite receiving informed consent, there are indicationsthat participants remain ignorant about important as-pects of a trial in both the short term [29,30] and thelong term [31]. Trial staff and investigators should givehigh priority to the informed consent process so thatparticipants understand what is involved in trial par-ticipation. Providing pertinent information about thetrial and trial-related issues should be an ongoing pro-cess that spans the duration of the study. Study news-letters can greatly facilitate this information-givingprocess [16]. Investigators and staff should maintainregular contact with study participants throughout thetrial to reinforce enthusiasm for the study and to pro-mote adherence [1].

Immediate attention to participant adverse events,whether self-reported or measured, is essential. Quickfollow-up on participant concerns and inquiries reflectsstaff/investigator dependability, credibility, and con-cern, as does the timely provision of appropriate clini-cal data (for example, certain diagnostic test results).Since participants communicate regularly with trialstaff by phone, good clinic phone coverage is essential.Uniform information from clinic staff/investigators im-plies that all trial personnel are familiar with clinicoperations, the study protocol, and the MOP, so that


participants receive consistent directions, advice, andresponses to their questions. Conveying sincerity, pa-tience, sensitivity, and recognition may require extraeffort and time; however, these attributes may enhancecompliance and retention. Another measure to improveparticipant compliance and retention relates to com-municating staff willingness to accommodate partici-pant needs (for example, scheduling clinic visits in theevenings or on the weekends) [28]. Trial personnelshould also maintain good professional integrity andprofessional appearance, which can lead to greater par-ticipant confidence in the staff and in the study. Table3 summarizes these communication strategies.

Commandment VIII: Thou Shalt Keep ThyParticipants’ Secrets

Participant confidentiality must be maintained dur-ing and after a clinical trial [2]. Efforts to ensure par-ticipant confidentiality include arranging maximal pri-vacy for interviewing, securing participant files toguard against their unauthorized use (participant filesshould never be left in undesignated areas of the clinicwhere other participants or nontrial employees couldlook through them), and having restricted access to thestudy database (only authorized personnel with properpasswords should be able to log on to the clinic com-puter). Finally, participant identifiers (name, photo-graph, identification or social security number) shouldnever be included in trial publications or presenta-tions, unless preapproved by the participant [2].

Commandment IX: Thou Shalt Revere Thy Data

Given the daily grind and bureaucracy involved inrunning a trial clinic, staff and investigators should bereminded occasionally that one of their primary goalsis the collection of high-quality data, which will allowthe study to answer an important medical questionthat could contribute to improved health care. This be-gins with proper training, certification, and standard-ization [32]; scrupulous data collection [33]; transcrip-tion and source documentation, and awareness of andinvolvement in quality control efforts.

Those coordinating clinic operations should build inpersonnel time and effort to review the data collectionforms for completeness, consistency, and accuracy be-fore their timely entry into the study database. Re-sponses to coordinating center inquiries about ques-tionable data should be prompt. Backups of the localdatabase should be performed daily, and, if distributeddata entry is not utilized, data should be downloadedand forwarded to the coordinating center according tothe study-dictated schedule. Training, certification,and recertification of staff (and sometimes investiga-tors) are laborious but necessary to maximize the like-lihood of obtaining consistent measures within and be-tween trial staff.

Clinics utilizing the services of a local outside facility

for study purposes (laboratory analyses, mammogram,or bone scan site) should work closely with facility staffto promote adherence to protocol guidelines (perform-ing standardized procedures/measurements, propercompletion of the data collection forms, etc.).

Quality assurance efforts cover a spectrum of activi-ties in a trial clinic. These include, but are not limitedto, assuring: (1) the safety of study participants (forexample, training staff to properly monitor and docu-ment adverse and clinical events that may or may notbe related to study participation); (2) the integrity ofthe informed consent process, randomization, andblinding; (3) protocol-dictated delivery of and adher-ence to the intervention, including timely participantfollow-up visits and primary/secondary outcome mea-sures; and (4) systematic monitoring of study data(data editing, correction, and analysis).

Commandment X: Thou Shalt Know and AcceptThy Limitations

Trial coordinators (as well as other clinic personnel)are at risk for burnout, because, in great part, suchdemanding positions attract dedicated and hard-working individuals who place many demands onthemselves. There is also the broad spectrum of coor-dinator duties that can be especially overwhelming tothose new to this position [16].

Conducting a clinical trial is a collaborative effortthat implies shared responsibility in its operation andmanagement. No one individual, not even the trial co-ordinator, should be expected to perform an unrealisticnumber of tasks. Cross training and back-up strategiescan partially guard against staff burnout. However,study investigators need to be sensitive to this loomingthreat, which can significantly slow down trial prog-ress if burnout leads to job resignation.

Arrangements should be made for trial staff and in-vestigators to occasionally meet socially in and out ofthe clinic. Earned vacations should be taken at mutu-ally agreed upon times. Staff incentives (e.g., closingthe clinic for one day when interim recruitment goalsare attained) can prove to be real motivators. Person-nel should be encouraged to vent their work-relatedfrustrations by discussing their concerns with their su-pervisors.

CONCLUSION

Although we have tried to cover major points relatedto clinical trial management, the topics discussed andthe examples given are not all-inclusive. We do feelthat the ten commandments addressed in this reporthave relevance to other types of epidemiological inves-tigations beyond clinical trials, such as observationalstudies.

The information and recommendations provided inthis paper are based on the multicenter clinical trialexperience of the authors, who have been involved in


Phase III clinical trials conducted in an academic en-vironment. We therefore cannot address other types ofresearch settings, such as earlier phase trials or phar-macokinetic studies, nor can we offer advice specific tothose working in a contract research organization,which conducts trials sponsored by industry. Althoughwe feel certain that the ten commandments discussedwould apply to these settings, it would be very usefulfor those working in these environments to put forwardtheir own experiences and recommendations concern-ing how best to manage a clinical trial.

Some examples cited in this report fall under morethan one commandment (communications with partici-pant physicians are described under CommandmentsII and V). Although this leads to some redundancy, wefelt that these topics merited discussion under the twodifferent categories.

If one were to highlight the major challenges andsources of frustration encountered in managing a trialclinic, the list would probably include the heroic effortsneeded to achieve the recruitment goal [22,25,28,34],insufficient funding, the constant and demanding bur-den of paperwork [22] and documentation, the unend-ing vigilance needed to maintain participant and staffcompliance with the protocol, challenges faced in re-taining participants in the study, and personnel turn-over (more of a threat to longer running trials). Per-sonnel turnover may be due to frustrations originatingfrom inadequate staffing to get the job done, lack of PIsupport and involvement, insufficient autonomy, mis-guided expectations, unrealized salary expectations,lack of job security, and personnel conflict (for example,troublesome colleagues who either fail to contributetheir expected workload or bring conflict rather thancollaboration to the work setting). Staff turnover canimpede trial progress, whether it occurs during theearly [35] or later stages of a trial.

Principal investigators and clinic supervisory staffshould do everything possible to make job conditions asreasonably pleasant, harmonious, productive, and effi-cient as possible. This too can be a daunting challenge,given today’s budgetary constraints. Maintaining agood sense of humor (no costs involved) can prove to beespecially valuable as a stress reliever.

The positive aspects of working in a trial clinicshould be emphasized. These include collaboration,contribution to science and improved public health, pa-tient contact, intellectual stimulation, job diversity,publication, and sometimes travel opportunities. Ex-pecting the unexpected could be considered a positivefactor for creative individuals who enjoy new chal-lenges.

The day-to-day problems faced in managing a clini-cal trial can obscure the reasons for initially becominginvolved in medical research. The following excerptedquote by D. S. Fredrickson [36] sums up the frustra-tions faced and ultimate ‘‘raison d’etre’’ for performing

human research studies (referred to as ‘‘field trials’’ inhis article).

[Field trials] . . . lack glamour; they strain our resources andpatience, and they protract to excruciating limits the moment oftruth. Still, they are among the most challenging tests of ourskills . . . I have no doubt that when the problem is well chosen,the study is appropriately designed, and all the population con-cerned made aware of the route and the goal, the reward can becommensurate with the effort. If, in major medical dilemmas,the alternative is to pay the cost of perpetual uncertainty, havewe really any choice?

ACKNOWLEDGMENT

The authors thank Dr. Roger Anderson, Dr. Walter Ettinger, Ms.Beate Griffin, Ms. Patricia Hogan, and Dr. Electra Paskett for theirwillingness to review the manuscript and to provide valuable com-ments, which have enriched the paper.

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Ten Commandments of Successful Trial Management