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Hypothesis/Commentary Accelerating Translation of Physical Activity and Cancer Survivorship Research into Practice: Recommendations for a More Integrated and Collaborative Approach Siobhan M. Phillips 1,2 , Catherine M. Alfano 1 , Frank M. Perna 3 , and Russell E. Glasgow 2,4 Abstract Physical activity has been deemed safe and effective in reducing many negative side effects of treatment for cancer survivors and promoting better overall health. However, most of this research has focused on highly controlled randomized trials and little of this research has been translated into care or policy for survivors. The purpose of the present article is to present a research agenda for the field to accelerate the dissemination and implementation of empirically supported physical activity interventions into care. We provide rationale for the role of basic, behavioral, clinical implementation, and population scientists in moving this science forward and call for a more coordinated effort across different phases of research. In addition, we provide key strategies and examples for ongoing and future studies using the RE-AIM (reach, efficacy/effectiveness, adoption, imple- mentation, and maintenance) framework and pose recommendations for collaborations between researchers and stakeholders to enhance the integration of this research into policy and practice. Overall, we recommend that physical activity and cancer survivorship research use additional study designs, include relevant stakeholders, and be more collaborative, integrated, contextual, and representative in terms of both setting and participants. Cancer Epidemiol Biomarkers Prev; 23(5); 687–99. Ó2014 AACR. Introduction There are an estimated 14 million cancer survivors in the United States with this number expected to increase to 18 million over the next decade (1, 2). Cancer and its treatment are associated with deleterious psychosocial and physical side effects that may be chronic or have a delayed onset and result in compromised quality of life (QOL; ref. 3). In addition, cancer survivors are at increased risk for developing comorbid conditions (4, 5) and second primary cancers (6, 7) as well as premature mortality (8). Evidence indicates increased physical activity in cancer survivors is associated with reduced negative treatment– related side effects, enhanced QOL, and improved dis- ease-specific outcomes (i.e., longer survival, reduced risk of recurrence, and mortality; refs. 9–17). Consequently, guidelines recommending physical activity for all cancer survivors (18, 19) have been developed. Despite the benefits of physical activity, cancer survi- vors are at least as inactive, or more inactive, than the general population (20–22) and other populations with chronic conditions (23–25). Population-based estimates indicate that only about one-quarter to one-third (20– 22, 26) of survivors meet the public health recommenda- tions for aerobic or strength training activities. Although many factors (e.g., demographics, prediagnosis activity, disease and treatment characteristics, symptoms, and behavioral and socioenvironmental factors; refs. 27–32) may contribute to dismal activity levels in this population, the lack of widely available disseminable evidence-based physical activity programs for cancer survivors (33) may be particularly detrimental. A good example of this is the fact that only one such program has been included in the Research-Tested Intervention Programs database (http://rtips.cancer.gov/rtips/index.do). This is likely reflective of most physical activity interventions for can- cer survivors being designed as randomized clinical trials (RCT) that, by design, are time and resource intensive and often ignore, or hold constant, individual (e.g., interven- tion delivery preferences, motivational factors, comorbi- dites, and symptoms) and contextual (e.g., resources, safety, and cost) factors that influence real-world inter- vention uptake and sustainability (33). Although efficacy studies have been important to establish the evidence base for the beneficial effects of physical activity, the inherent limited generalizability of this research precludes wide- spread dissemination and implementation (D&I; ref. 19). Although some recent studies have adopted more prac- tical study designs in real-world settings (34–38), increas- ing the number of these types of studies and enhancing the Authors' Afliations: 1 Ofce of Cancer Survivorship; 2 Implementation Sciences Team; 3 Health Behaviors Research Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD; and 4 Colorado Health Outcomes Program, University of Colorado, Boulder, Colorado Corresponding Author: Siobhan M. Phillips, National Cancer Institute, 9609 Medical Center Drive, Ofce 4E516, Rockville, MD 20850. Phone: 240-276-6939; Fax: 240-276-7908; E-mail: [email protected] doi: 10.1158/1055-9965.EPI-13-1355 Ó2014 American Association for Cancer Research. Cancer Epidemiology, Biomarkers & Prevention www.aacrjournals.org 687 on July 7, 2020. © 2014 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from Published OnlineFirst March 5, 2014; DOI: 10.1158/1055-9965.EPI-13-1355

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Hypothesis/Commentary

Accelerating Translation of Physical Activity and CancerSurvivorshipResearch intoPractice: Recommendations for aMore Integrated and Collaborative Approach

Siobhan M. Phillips1,2, Catherine M. Alfano1, Frank M. Perna3, and Russell E. Glasgow2,4

AbstractPhysical activity has been deemed safe and effective in reducing many negative side effects of treatment for

cancer survivors and promoting better overall health. However, most of this research has focused on highly

controlled randomized trials and little of this research has been translated into care or policy for survivors. The

purpose of the present article is to present a research agenda for the field to accelerate the dissemination and

implementation of empirically supported physical activity interventions into care.Weprovide rationale for the

role of basic, behavioral, clinical implementation, and population scientists inmoving this science forward and

call for amore coordinated effort across different phases of research. In addition,we provide key strategies and

examples for ongoing and future studies using the RE-AIM (reach, efficacy/effectiveness, adoption, imple-

mentation, and maintenance) framework and pose recommendations for collaborations between researchers

and stakeholders to enhance the integration of this research into policy and practice. Overall, we recommend

that physical activity and cancer survivorship research use additional study designs, include relevant

stakeholders, and be more collaborative, integrated, contextual, and representative in terms of both setting

and participants. Cancer Epidemiol Biomarkers Prev; 23(5); 687–99. �2014 AACR.

IntroductionThere are an estimated 14 million cancer survivors in

theUnited Stateswith this number expected to increase to18 million over the next decade (1, 2). Cancer and itstreatment are associated with deleterious psychosocialand physical side effects that may be chronic or have adelayed onset and result in compromised quality of life(QOL; ref. 3). In addition, cancer survivors are at increasedrisk for developing comorbid conditions (4, 5) and secondprimary cancers (6, 7) as well as premature mortality (8).Evidence indicates increased physical activity in cancersurvivors is associated with reduced negative treatment–related side effects, enhanced QOL, and improved dis-ease-specific outcomes (i.e., longer survival, reduced riskof recurrence, and mortality; refs. 9–17). Consequently,guidelines recommending physical activity for all cancersurvivors (18, 19) have been developed.Despite the benefits of physical activity, cancer survi-

vors are at least as inactive, or more inactive, than the

general population (20–22) and other populations withchronic conditions (23–25). Population-based estimatesindicate that only about one-quarter to one-third (20–22, 26) of survivors meet the public health recommenda-tions for aerobic or strength training activities. Althoughmany factors (e.g., demographics, prediagnosis activity,disease and treatment characteristics, symptoms, andbehavioral and socioenvironmental factors; refs. 27–32)may contribute to dismal activity levels in this population,the lack of widely available disseminable evidence-basedphysical activity programs for cancer survivors (33) maybe particularly detrimental. A good example of this isthe fact that only one such program has been includedin the Research-Tested Intervention Programs database(http://rtips.cancer.gov/rtips/index.do). This is likelyreflective of most physical activity interventions for can-cer survivors being designed as randomized clinical trials(RCT) that, by design, are time and resource intensive andoften ignore, or hold constant, individual (e.g., interven-tion delivery preferences, motivational factors, comorbi-dites, and symptoms) and contextual (e.g., resources,safety, and cost) factors that influence real-world inter-vention uptake and sustainability (33). Although efficacystudies havebeen important to establish the evidence basefor the beneficial effects of physical activity, the inherentlimited generalizability of this research precludes wide-spread dissemination and implementation (D&I; ref. 19).Although some recent studies have adopted more prac-tical study designs in real-world settings (34–38), increas-ing thenumber of these types of studies andenhancing the

Authors' Affiliations: 1Office of Cancer Survivorship; 2ImplementationSciences Team; 3Health Behaviors Research Branch, Behavioral ResearchProgram, Division of Cancer Control and Population Sciences, NationalCancer Institute, Rockville, MD; and 4ColoradoHealth Outcomes Program,University of Colorado, Boulder, Colorado

Corresponding Author: Siobhan M. Phillips, National Cancer Institute,9609 Medical Center Drive, Office 4E516, Rockville, MD 20850. Phone:240-276-6939; Fax: 240-276-7908; E-mail: [email protected]

doi: 10.1158/1055-9965.EPI-13-1355

�2014 American Association for Cancer Research.

CancerEpidemiology,

Biomarkers& Prevention

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generalizabillity of new and existing efficacy/effective-ness studies is a critical next step for moving research inthis area forward (39–44). We recognize that there aresome trials (e.g., those answering biologic mechanism ordose questions) in which not all suggestions provided arefeasible to implement (e.g., these likely need to be con-ducted in controlled laboratory settings). However, evenin these cases, investigators can take some steps toimprove the eventual translation of their findings, forexample, by including a more representative sample ofsurvivors.

Factors limiting D&I of physical activity and cancersurvivorship research are consistent with other scientificdisciplines and include a predominant focus on discov-ery; limited study relevance and efficiency; and inade-quate collaboration and coordination among scientists(basic, clinical, population, and implementation) and sta-keholders (45–47). Fortunately, many existing limitationscan be addressed through the application of two frame-works: (i) the translational research process (45–48) and(ii) RE-AIM (reach, efficacy/effectiveness, adoption,implementation, and maintenance; ref. 49). The transla-tion research process identifies five phases for translatingscientific discovery topopulationhealth impact (see Fig. 1;refs. 45–48). Each phase answers a different question, usesdifferent methods, and informs every other making thisframework particularly useful for identifying exactlywhat research is needed and how research at every phase(e.g., basic, clinical, behavioral, implementation, and pop-ulation) can be more collaborative and coordinated (45–48). RE-AIM is a conceptual model designed to enhance

quality, speed, andpublic health impact of efforts tomoveresearch into long-term effectiveness in real-world set-tings (49) and can be used to provide specific study designrecommendations to enhance the contribution of eachtranslational phase (T0–T4) in achieving the ultimate goalof translating physical activity and cancer survivorshipresearch into practice.

The purpose of the present article is to (i) summarizekey facilitators for translating physical activity andcancer survivorship research into practice; (ii) recognizethe importance of each T0 to T4 phase, highlight its rolein translating research in this area to practice and arguefor a more coordinated approach to advance this sci-ence; and (iii) provide specific recommendations foreach RE-AIM element to accelerate the translation ofphysical activity and survivorship research into policyand practice.

Five Phases of Translational ResearchThe translational research process consists of five

phases (T0–T4; see Fig. 1) that provide guidance aboutwhat is needed to successfully develop, implement, andsustain evidence-based approaches in real-world settings(45, 46). The translational process starts with the "discov-ery" of an opportunity to approach a health issue (T0). Thefirst phase (T1) involves research from,mechanistic, basicbehavioral, or clinical research resulting in the develop-ment of tests or clinical and nonmedical (i.e., policy,behavioral, social, or other public health interventions)interventions (45, 46). The second phase (T2) involvesrigorous analysis and investigation of new intervention

T3

T1

T2

T4

T0

Modified from Alfano et al. [48] and Lam et al. [51]

Effect of physical

activity on the health

and disease burden

of survivors at

population level

Promising physical

activity applications

and interventions

for cancer survivors

Evidence-based

physical activity

recommendations,

guidelines, or

policies for cancer

survivors

Physical activity

programs for cancer

survivors in practice,

organization, and

community settings

Describe

health outcomes

and determinants

Mechanisms; preclinical studies;

phase I and II trials

Evaluation of interventions

(phase III trials)

Implementation and

dissemination in real-world settings

Evaluating outcomes in

real-world settings

Collaboration

Knowledge integration

Iterative feedback

Scientific discovery of

effects of physical

activity on health and

disease outcomes

in cancer survivors

Figure 1. The translational scienceprocess for physical activity andcancer survivorship.

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effects for improving health outcomes resultant in evi-dence-based guidelines and recommendations (45, 46).The third phase (T3) consists of investigations to increaseuptake and implementation of evidence-based recom-mendations into practice. The final phase (T4) involvesevaluation of intervention effectiveness/cost-effective-ness in real-world settings and population or publichealth impact.Akey characteristic of the translational researchprocess

is that it is nonlinear. Each phase is important and nec-essary, leads to new insights that fuel discoveries andcontributes to knowledge integration by informing eachand every other phase to, ultimately, enhance translationof science into practice (see Table 1). The translationprocess is driven by (i) ongoing and updated knowledgeintegration from basic, clinical, and population sciences;(ii) collaboration and transdisciplinary team science (50);(iii) multilevel analyses and interventions; and (iv) tech-nology (51). Consequently, to accelerate translation, acollaborative, coordinated approach is needed amongstakeholders and researcher across phases. Althoughstudies must be designed to answer phase-specificresearch questions, the other phases and overall end goalof translating discovery into practice should be kept inmind. For example, although the main purpose of a T2studymay be to determine the efficacy of physical activityfor fatigue reduction, the studymaybedelivered remotely(i.e., web based) with limited on-site appointments, ifappropriate, thereby facilitating T3 and T4 research byusing a more practical and feasible approach. Table 1provides detailed examples, research needs, and role intranslation for physical activity and survivorship researchfor each T0 to T4 phase.Most physical activity and survivorship research has

consisted of observational studies and phase II clinicaltrials (T0–T2) examining the effects of physical activity onspecific health and disease-related outcomes (45, 46). It isessential for research in this area to progress beyond T2 toinclude activities to drive translation of research findingsinto practice and policy (47). However, it is also necessaryto balance the requirement for more practical, effective-ness research with the limited efficacy data currentlyavailable for the many potential combinations of activitycharacteristics and health outcomes (43). Because thecurrent funding environment limits the feasibility of con-ductingRCTs for every exposure and outcome (52), itmaybe necessary to adopt the Institute of Medicine mantra "toact on the best evidence available" (53) and draw fromstudies other than traditional RCTs, including systems’dynamic models (54), N-of-1 (55, 56), comparative effec-tiveness research (CER; ref. 57), and fractional factorialdesigns [i.e., multiphase optimization strategy trials(MOST) and sequential multiple assignment random-ized trials (SMART; ref. 58)]. This approach embracesthe nonlinear nature of the translational research pro-cess and has the potential to simultaneously contributeto the evidence base, inform practice and policy, and,ultimately, move research in this area forward.

Factors Influencing D&I of Physical ActivityResearch in Cancer Survivors across T0 to T4

Figure 2 presents examples of factors that have con-strained widespread D&I of physical activity interven-tions for survivors across T0 to T4 research. These factorsinclude intervention characteristics, target setting context,research design, healthcare system factors, knowledgeabout physical activity behavior, physical activity mea-surement, and definitions and interactions among thesefactors (59–62). In addition,most studieshavenot engagedstakeholders (e.g., survivors; oncologists; and communityorganizations; nurses, administrators, and families;ref. 43). Failure to address these factors limits potentialD&I and sustainability of existing interventions by reduc-ing their feasibility, adaptability, and relevance to cancersurvivors and intervention delivery systems (e.g., hospi-tals, community centers; refs. 52, 63).

Enhancing D&I Potential of Physical Activity andSurvivorship Research across T0 to T4

Ongoing and future research can contribute to over-coming barriers to D&I of physical activity and survivor-ship research. As detailed in Table 1, researchers at everyT0 to T4 phase can contribute to translation withoutbecoming a D&I scientist. This is only possible, however,if researchers adopt a collaborative coordinated transdis-ciplinary approach (50) and involve relevant stakeholdersto integrate knowledge, ask novel research questions anddesign innovative and transformative studies (51). Tooptimize chances of success, investigators in every phaseshould consider the real-world context inwhich survivorslive and attempt to incorporate this context in their science(52) by adequately mimicking the real-world clinical con-text (e.g., treatment protocols, symptoms), disease expe-rience (e.g., cooccurring conditions, treatment toxicities),patient diversity/complexity (e.g., multiple chronic con-ditions, age), and variability in protocol adherence (64).These factors should be considered by T1 researchers indeveloping preclinical and humanmodels (64) and along-side practice-based evidence (i.e., characteristics of inter-ventions that have previously worked or failed in real-world settings) for T2 to T4 researchers (59).

Figure 3 uses cardiovascular disease (CVD) preventionto illustrate how these principles can be applied in a morecoordinated and collaborative manner. The initial stepwould be to form transdisciplinary scientific and stake-holder teamswhowill be actively engaged throughout theresearch process. First, scientists would corroborate withstakeholders to understand their needs, experiences,resources, and expectations with regard to factors thatmay influence the likelihood a physical activity programwould be adopted, implemented, and maintained atboth an individual (e.g., intervention setting, time com-mitment, and type of activity) and systems/setting level(e.g., staffing, time, and resources). It is importantto recognize that stakeholder and researcher needs maynot always be complementary. For example, although

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Table 1. Physical activity and cancer survivorship—stages of translational research examples, researchneeds, and translational impact

Key drivers across all phases: collaboration, knowledge integration, technology, multilevel interventions, and analyses

Researchphase Example(s) Research needs Translational impact

T0 * Discovery that exercise isassociated with reductions inmetabolic syndrome in cancersurvivors

* Discovery that exercise isassociated with increaseddisease-free survival

* Examine physical activity inrelation to chronic conditions, functionaloutcomes, cancer progression, survival,and potential intermediary endpoints

* Examination of these relationshipsin diverse cancer types

* Assessment of effects of dose–responseusing observational data

* Provide scientific justificationfor future research

* Identify exercise dosage forfuture intervention studies

T1 * Initial pilot physical activityintervention trial to examinethe relationship betweenexercise and development ofmetabolic syndrome

* Initial pilot physical activityintervention trial to examineinflammation as a potentialmechanism underlying thesurvival benefits of physicalactivity

* Cost–benefit analyses of physical activityin comparison with other currentlyavailable approaches to symptom anddisease management

* Animal and human models of exerciseand cancer survivorship that mimic oneanother and the real-world

* Determination of potential mechanismsunderlying the health benefits for physicalactivity (e.g., aerobic fitness) andidentification of intermediary markers forprognosis and survival

* Provide scientific justificationfor widespread implementationof physical activity interventions

* Determine safety of physicalactivity interventions

* Mechanism data provideevidence for third partyreimbursement and morepersonalized physical activityrecommendations

T2 * Large intervention trial totest the effects of physicalactivity on lymphedema inbreast cancer survivors

* Replication of efficaciousphysical activity interventionsin low-resource settings

* Development of evidence-based physical activityprograms and physicalactivity guidelines

* Common metrics for comparison* Innovative; more practical study designs* More diverse participants* Multisite collaborations* Fractional factorial and pragmatic trialsto determine most effective interventioncomponents and physical activity dosage

* Studies to determine the MINC forspecific health benefits

* Use of technology to increaseintervention reach

* Synthesis of evidence to overcomebarriers to physical activity participation

* Evidence of long-term efficacy ofphysical activity intervention on behavioraland health outcomes

* Multilevel analyses of factors influencingphysical activity participation andintervention effectiveness

* Strengthen evidence base* Provide evidence-basedinterventions to be tested indiverse settings

* More generalizable findings;reductions in health disparities

* Reduce implementation costsand increased interventionuptake

* Facilitate development ofindividualized physical activityprogram recommendations

* Increase focus on contextand boundary conditions ofeffects

T3 * Implementation of evidence-based physical activityprograms in multiple,diverse. and low-resourcereal-world settings

* Implementation of evidence-basedprograms in multiple, real-world settings

* Contextual assessment* Standardized intervention and trainingmaterials

* Prevent and reduce sideeffects of cancer and itstreatments at more globallevel

(Continued on the following page)

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researchers and clinicians may be interested in CVD riskas an outcome, this may not be an important outcome tosurvivors. Thus, compromise may be required to achieveinterventions and assessments amenable to both groups.Next, researchers would conduct rapid and recursivestudies to refine preclinical and human models integrat-ingdata from the laboratory, stakeholders, and real-worldimplementation. This process would continue until theintervention strikes the proper balance of feasibility andeffectiveness and maximizes the likelihood clinical andreal-world environments mimic one another and effectestimates are accurate. The resulting physical activityintervention and prescription(s) would be safe, effica-cious for improving CVD risk factors (e.g., cardiorespi-ratory fitness, lipid profile), and supported by stake-holders (52). The intervention could then be replicatedin diverse settings to determine feasibility and effec-tiveness. Finally, when appropriate, interventionswould be broadly disseminated and effects on CVD incancer survivors could be monitored at the population-level using existing data sources (e.g., Behavioral RiskFactor Surveillance System; National Health InterviewSurvey; ref. 65).Although an integrated collaborative approach incor-

porating D&I from the start may be ideal, (66) it may notalways be possible and is not without challenges. Regard-less, immediate steps can be taken to enhance studyrelevance and D&I potential. We use RE-AIM to outlinespecific recommendations for enhancing D&I of physical

activity and survivorship research across the T0 to T4phases.

RE-AIMRE-AIMhas been used inmore than 200 studies to plan,

evaluate, and review health promotion and disease man-agement interventions (67, 68) and is intended for use atall stages of research, from planning to evaluation tosyntheses (68, 69). The five dimensions (RE-AIM) arerelated to internal and external validity and incorporateindividual and setting levels. Applying these five dimen-sions to physical activity and survivorship research canaddress key issues in translation and increase the prob-ability of D&I of this research into policy and practice.

RE-AIM recommendations for enhancing D&Ipotential across T0 to T4

Elements of these recommendations are intended toapply across T0 to T4, including basic, behavioral,clinical, and population sciences (45, 46). Overall, werecommend research in this area maintain its rigor, butstrive to be more rapid, relevant, robust, recursive, andtransparent (47, 70). Recommendations for each RE-AIM element are intended to encourage clinically rel-evant research that leverages existing resources andinfrastructure, uses more efficient and innovativeresearch designs and mixed methods (52, 71), andincorporates relevant stakeholders (43). Furthermore,adoption of a solution-oriented approach focused on

Table 1. Physical activity and cancer survivorship—stages of translational research examples, researchneeds, and translational impact (Cont'd )

Key drivers across all phases: collaboration, knowledge integration, technology, multilevel interventions, and analyses

Researchphase Example(s) Research needs Translational impact

* Assessment of factors thatinfluence interventionsuccess and implementation

* Examination of the broaderimpacts of physical activity(e.g., QOL) and unintendedconsequences (e.g., sedentarybehavior)

* Multilevel analyses of factors influencingphysical activity participation andintervention effectiveness

* Assessment of factors that influence thesuccess of the intervention andimplementation

* Establish optimal interventionimplementation strategies

* Establish sustainableinfrastructure

* Provide affordable, effectivephysical activity programs

* Provide data on broaderimpacts of physical activityparticipation in cancer survivors

T4 * Measurement of physicalactivity and prevalence oftargeted interventionoutcomes (e.g., diabetes,depression) in survivors at thepopulation level

* Cost-effectiveness analyses forimplementing evidence-basedinterventions in practice

* Pooling of data resources that monitorphysical activity behavior of cancersurvivors

* Pooling of data resources with behavioraland medical usage data

* Focus on key institutions providing cancercare to conduct quality improvementprojects

* Inform policy development,future discovery, andintervention development

* Potential improvements inquality of care/patientexperience and populationhealth and reducedhealthcare costs

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improving the health of cancer survivors through phys-ical activity in a sustainable way is encouraged over aproblem-oriented, reductionist approach focused solelyon understanding cause and effect relationships betweenactivity and health outcomes (72). Finally, as single inter-ventions are generally insufficient to create sustainablechange, multilevel and multistrategy approaches arerecommended (73, 74). Key strategies for addressing eachRE-AIM element and examples of how to use these strat-egies in ongoing and future studies are detailed in Table 2and described below.

ReachAlthough well-defined homogenous samples are often

considered hallmarks of rigorous research, they also maylimit applicability of findings to real-world heterogeneouspopulations (75). Existing physical activity and cancersurvivorship study samples mainly consist of breast can-cer survivors who are middle-aged, White, English-speaking, and high socioeconomic status (33), which is

not entirely representative of the survivor population (2).The representativeness of experimental, intervention, andobservational study samples should be increased to pro-vide more accurate estimates of effects and cost-effective-ness (76).

Specific strategies and recommendations for improvingreach are detailed in Table 2. First, concerted and iterativeefforts should be made to recruit harder to reach cancersurvivors using methods including bilingual staff, trans-lated and culturally adapted intervention materials, com-munity leaders (77), and snowball sampling techniques(78). Second, study eligibility criteria should be expandedto include survivors over age 65, beyond 5 years afterdiagnosis and/or those with other chronic conditions(2, 79). Data also need to be collected to compare partici-pants and nonparticipants. Ideally, this would be accom-plished through waivers of informed consent to obtainbasic demographic and health status data on nonpartici-pants for comparison. If this is unfeasible, study sam-ples should be compared with the local survivor

Intervention characteristics

• Intense, high cost, on-site interventions in high-resource settings

• High level of expertise required to deliver intervention

• Inflexible programs that are not adapted or tailored to meet the needs of survivors

• Not “packaged” or manualized

• Survivors may not want to travel to cancer centers to participate

Target setting context

• Lack of time and resources for physical activity programs

• Competing demands

• Physical space restrictions

• Limited staff with expertise in physical activity

• Limited organizational support

• Specific needs or situations limit ability to implement

Research design

• Exclude those with co-occurring chronic conditions

• Nonrepresentative, homogenous samples

• Failure to evaluate cost/implementation

• Do not involve stakeholders (e.g., survivors; nurses; and community leaders)

Measurement/definitions of physical activity

• Self-report vs. objective measures

• Inclusion of all types of activity vs. only including moderate/ vigorous intensity activity

• Meeting public health guidelines vs. increasing activity more generally

• Different physical activity modalities (walking vs. strengthvs. yoga)

Health care system factors

• Clinicians believe not enough evidence to support

• Impression that exercise might be harmful

• Little value placed on outcomes other than survival

• More generalizable populations used are viewed negatively

• No referral pathways or reimbursement mechanisms for physical activity programs

Knowledge about physicalactivity behavior

• Little known about cancer survivors’ knowledge, barriers, environment, motivation

• Do not know full value added of physical activity for caner survivors

• What works for whom?

• Frequency

• Intensity • Duration

• Type • Outcome specific?

[33,45,47,48]

Interaction

among factors

Figure 2. Examples of factors influencing D&I of current physical activity and cancer survivorship research into practice.

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Assessment of population-level effects

Scientists: Analyze effects on health outcomes, costs/benefit of interventions, and sustainability

Stakeholders: Support sustainability

Broad intervention dissemination

Scientists: Evaluate effectiveness on health/ behavioral outcomes; assess RE-AIM; evaluate feasibility, unintended consequences, and sustainability

Stakeholders: Provide support and facilitate sustainability

Intervention replication in diverse populations/settings

Scientists: Evaluate and refine interventions based on setting needs; assess RE-AIM

Stakeholders: Provide feedback and insight into success and failures; provide resources, settings, and support for intervention replication

Intervention refinement

Scientists: Balance effects vs. feasibility; consider context, reach, adoption, behavior maintenance, sustainability, unintended consequences, and costs

Stakeholders: Provide feedback/ insight into success and failures; provide resources, settings, and

support for testing interventions

Small, rapid recursive exercise protocol/intervention studies

Scientists: Test effects and underlying mechanisms; consider context and cost; and integrate stakeholder feedback

Stakeholders: Support intervention testing; provide feedback aboutfeasibility and necessary protocol changes

Assess/prioritize both parties’ needs and perceptions

Scientists: Balance relevance, rigor, scalability in intervention/protocol design; and consider context

Stakeholders: Provide researchers with data/knowledge about context (e.g., feasibility, available resources, support) and outcome(s) deemed important

Interdisciplinary researchers and stakeholders collaborate

Scientists: cardiologists, oncologists, basic, clinical, behavioral, D&I population scientists; and economists

Interactive working group formed with

specific interests and challenges of each

side; represented; meets regularly; all

major decisions must be agreed upon

Decide to pursue tapered on-site to home-

based technology supported walking

program with goal of 150 min/wk based

on stakeholders concerns about feasibility

and researchers concerns about fidelity

Example(s)/outcome(s)

Experiments to determine effect of

timing/dose of intervention on CVD

indicators (of interest to scientists) and

physical function (of interest to

stakeholders) reveal exercise should be

started pretreatment and continued

through to posttreatment; time is reduced

to 100–120 min/week

Modify program to allow participants to

choose tapered or all home-based

program based on stakeholder feedback,

cost effectiveness analysis, and

measurement of RE-AIM elements;

reveal increased sitting time is unintended

consequence and develop plan to prevent

Program is packaged, delivered, and found

to be effective in academic and

community cancer centers and community

centers; supported by rich network of

stakeholders

Tapered and/or home-based intervention

is offered to most cancer survivors as part

of standard of care; provides cohort of

survivors to study as part of natural

experiment

Program is maintained and risk factors for

CVD decline as measured by existing

national surveys

Stakeholders: cancer survivors, nurses, rehabilitation specialists, and community leaders

Figure 3. A more coordinated and integrated approach for translating research into practice: Exercise to prevent CVD in cancer survivors as anexample.

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Table 2. Key strategies across T0 to T4 research phases for ongoing studies

Definition Key strategiesExamples—both ongoingand future studies

Examples specific tofuture studies

Reach The absolutenumber, proportion,and representativenessof individualswho are willing toparticipate in agiven initiative

* Collect data onnonparticipants and usemixed methods tounderstand whypeople do notparticipate ordropout

* Increase recruitmentefforts to hard toreach populations

* Expand eligibility criteriafor interventions andobservational analyses

* Assess demographics/health status ofnonparticipants

* Involve key communityleaders; snowballrecruitment

* Include individuals withother chronic conditionsand those �65 whenpossible

* Interview participants,nonparticipants anddropouts

* Incorporate evaluabilityprocedures to assessReach and othercomponents below

Efficacy/effective-ness

The impact of anintervention onimportantoutcomes,includingpotential negativeeffects, QOL, andeconomicoutcomes

* Track unanticipated/adverse events

* Study moderating factorsand subgroup effects

* Determine MINC* Use practical, standardizedmeasures

* Collect data on contextualand individual factorsand other behaviors

* Interview participantsand dropouts

* Assess if participants usingany other physical activitysupports or resources

* Report on outcomes by keyhealth disparities

* Collect data on physicalactivity beyondadherence tointervention protocol

* Coordinate with otherscientists to use commonmetrics for sameoutcomes

Adoption The absolutenumber, proportion, andrepresentativenessof settings andinterventionagents willing toinitiate a program

Setting level* Collect data onnonparticipatingsites or reasonsexcludeda

* Build partnershipswith survivors,clinicians, andorganizationalleadership

Setting level* Track importantcharacteristics (e.g.population served,location, size, etc.)of all sitesapproached toparticipate andreasons for ineligibility

Setting level* Use real-world settingand the comparisongroup

Staff level* Collect informationon characteristics ofparticipating andnonparticipating staff

* Track staff participation

Staff level* Interview staff atparticipating andnonparticipatingsites

Staff level* Use real-worldpractitioners asinterventiondelivery-agents

Implemen-tation

The interventionfidelity ofagents to the variouselements of theprotocol of anintervention,including consistencyof delivery as intended

* Assess resources andmonetary costs

* Document adaptationsneeded

* Create standardized trainingand delivery materials

* Assess consistency ofintervention implementation

* Track costs, includingtraining, staffing,assessments, physicalresources, and time

* Document challenges,barriers, and adaptations/solutions and any changesin the study protocol

* Allow for tailoring ofintervention componentsto setting

* Use nontraditionalresearch designs (e.g.,MOST, SMART,and CER) as appropriateto address likely challenges

(Continued on the following page)

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population (68). Finally, data on factors influencingparticipation decisions should be collected from parti-cipants, nonparticipants and dropouts. These recom-mendations are all relatively obtainable through proto-col amendments for ongoing studies.

Efficacy/effectivenessMost physical activity and survivorship studies have

beendesigned tomaximize efficacy and effectiveness (33).Thus, recommendations in this area are focused on report-ing of broader and potential negative, or unanticipated,outcomes and "understanding what works for whom inwhat situation for which outcomes" (80). Key strategiesand examples of how to increase efficacy/effectivenessare provided in Table 2.Although adverse events are typically tracked in accor-

dance with data safety and monitoring plans, these num-bers are not always reported in publications (33). Trackingand reporting of these events is crucial for identifyingspecific individual, delivery, or setting characteristicsinfluencing adverse events rates. In addition, broader andunanticipated consequences of physical activity interven-tions (e.g., increased sedentary behavior or caloric con-sumption) should be measured periodically as they mayhave important implications beyond intended effects (81,

82). Data should also be collected on use of physicalactivity resources other than the assigned intervention todistinguish true intervention effects (83).

A key factor in discerning what works for whom underwhat conditions for which outcomes is understanding thecontext in which interventions are (and are not) effective(84). Investigators should collect and report data on con-textual (e.g., organizational, environmental) and individ-ual (e.g., demographic,motivation) factors thatmay influ-ence intervention efficacy/effectiveness. These data canalso be used to conduct subgroup and moderation anal-yses to clarify differential intervention or dosage effects(84). Physical activity measurement should also beenhanced to test effects of activity characteristics (e.g.,type, volume) on various outcomes. Thismay consist of (i)supplementation of intervention adherence measureswith objective and/or self-reportmeasures; (ii) evaluationof physical activity atmore frequent time intervals beyondpre- and postintervention; and (iii) incorporation of awide range of physical activity dosages in analyses. Ulti-mately, these techniques could support identification ofthe minimal intervention necessary for change (MINC;refs. 85, 86). In this case the MINC would represent thelowest intervention intensity, expertise, and resourcesneeded to achieve a clinically significant improvement

Table 2. Key strategies across T0 to T4 research phases for ongoing studies (Cont'd )

Definition Key strategiesExamples—both ongoingand future studies

Examples specific tofuture studies

and the time and cost ofthe intervention

* Track how interventions wasimplemented by differentstaff members, settings,and across subgroupsof individuals

* Collect information onintervention settingcontext

* Use mHealth and eHealthintervention deliverymethods with less roomfor variability

Mainte-nance

Individual level:Long-term effects of aprogram on outcomes� 6 months afterintervention

Setting level:Extent to which aprogram or policybecomes institutionalizedor part of routineorganizational practicesand policies

Individual level* Include, basicminimal assessmentof physical activitymaintenance andintervention effects�6 months afterintervention

* Examine subgroupseffects overfollow-up period

* Incorporate maintenanceassessment period

* Interview participants aboutmaintenance of behavior

* Interview setting aboutmaintenance of intervention

* Assess and report anyprogram changes afterformal research evaluation

* Use mHealth and eHealthintervention deliverymethods that can bemaintained afterintervention

* Incorporate interventionsustainabilityassessment

Setting level* Assess maintenanceof intervention withinsetting �6 monthsafter intervention

aFor multisite interventions (49).

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in activity or a specific outcome for a specific group ofsurvivors under a particular set of conditions, whendelivered in a specific way (85, 86). Identification of theMINC for various outcomeswould provide a standard forcomparison for outcome improvements based on therelative cost of more intensive interventions as well asmore personalized activity recomendations for survivorsin terms of program/prescription characteristics (86).Finally, use of practical, standardized outcome measuressuch as validated single-item symptom assessments isrecommended to facilitate knowledge integration andmonitor congruence at multiple assessment levels (e.g.,clinical and population; ref. 87).

AdoptionSpecific recommendations for increasing adoption of

physical activity interventions for cancer survivors atthe setting and staff level are detailed in Table 2. First,researchers conducting single- and multisite interven-tions should focus on building partnerships within uni-versities, hospitals, cancer centers, and communities togarner support for their programs to increase eventualadoption potential. Future and ongoing interventionsshould track participating and nonparticipating sites(e.g., populations served, location, and size) and staff(e.g., education, training) characteristics (68). Staff adher-ence and qualitative data on contextual factors they feelinfluenced adoption should be collected. Finally, futurestudies should use a more pragmatic approach to inter-vention design, including using diverse real-worldand low-resource settings (i.e., YMCAs, rehabilitationfacilities, community centers, and worksites), clinicallyrelevant comparison groups (76), and practitioners asdelivery agents (e.g., American College of Sports Medi-cine–certified cancer exercise trainers, community healthworkers; ref. 39).

ImplementationImplementation can be facilitated through the use of

technology, replication in diverse settings, collection ofdata on intervention adaptations or protocol changes,costs, resource requirements (e.g., training, staffingequipment, and time), and value added (see Table 2;ref. 88). In addition, standardized training and inter-vention materials similar to EnhanceFitness (89) and Fitand Strong (90) physical activity programs for olderadults should be created for widespread D&I of pro-grams for cancer survivors. To increase adherence,future studies should consider permitting tailoring ofintervention components such as modality (e.g., onsite,telephone, and internet), start date, setting (e.g., group,individual), or physical activity type (e.g., walking,swimming, and aerobics) to meet setting or participantneeds (61). Investigators should also consider usingmore innovative intervention delivery and data collec-tion methods (e.g., internet, mHealth) and nontradition-al research designs [e.g., MOST (ref. 58), SMART, andCER (ref. 57)] to increase potential feasibility and sus-

tainability (91). Use of systems science models (92) and/or simulation modeling are also recommended for iden-tifying points of maximum leverage for interventions,effects of physical activity policies, and programs on avariety of outcomes, and unintended consequences (82).Finally, future studies should incorporate D&I modelsand measures in the study design (93, 94).

MaintenanceFew trials in cancer survivors incorporate any mainte-

nance period or assessment (33, 43). Table 2 providesspecific strategies and examples for monitoring and eval-uating interventionmaintenance at individual and settinglevels. Follow-up after intervention is necessary to eval-uate behavior change maintenance, program sustainabil-ity and maintenance, and potential delayed onset ofintervention effects. At a minimum, brief individual andsetting level physical activity behavior and/or programmaintenance assessments should be conducted at least 6months after intervention. In addition, individual andsetting level data should be collected to examine potentialcontextual (e.g., organizational support, interventioncost) or individual (e.g., health status, motivation) factorsthatmaydifferentiate thosewhomaintain from thosewhodo not (68). For settings or individuals that maintainprograms, intervention changes or modifications shouldbe examined.

Projects in the planning phase should consider usingmHealth or related lower cost, technologies to deliverinterventions to enhance their potential maintenance(52). Finally, significant effort should be directed towardenhancing setting level maintenance and sustainability.Promising approaches to enhance setting sustainabilityare (i) stakeholder involvement from the outset; (ii)modest intervention costs and resource demands; and(iii) alignment with the setting’s business core valuesand relevant reimbursement or return on investmentpolicies.

DiscussionDespite the benefits of physical activity for cancer

survivors, population-specific physical activity recom-mendations (19) and a process for implementing theseguidelines into clinical practice (95), most physicalactivity research has not been, and is not likely to be,disseminated and implemented into practice. If thisresearch is to move beyond T0 to T2 to have popula-tion-level effects, it is imperative researchers considerthe broader implications of their work within the largertranslational context and collaborate to advance sciencein this area.

It is strongly recommended that investigators at all Tphases (i) adopt a more relevant, transparent, collabora-tive, and transparent approach; (ii) attempt to addresselements of RE-AIM or other D&I frameworks; and (iii)consider these elements in planning, design, and through-out study execution. We highlight key contributions ofeach T phase of translational research and provide key

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strategies for incorporating RE-AIM elements across allphases with the goals of improving external validity ofongoing and future studies and increasing the speed andlikelihood research will influence practice and policy. Inaddition, we have provided recommendations for howscientists from different phases can collaborate with oneanother, survivors, and stakeholders to enhance researchvalue and relevance.A potential reaction is that the actions called for seem

unrealistic or impractical, especially given competingdemands, bad reporting, institutional requirements andpotentially limited funding mechanisms, and reviewpanels with expertise to facilitate these types of studies.Our response to this likely objection is 4-fold. First,several recommendations do not require additionaltime, effort or funding mechanisms, but recommenddoing things differently from the outset (e.g., thinkingabout eventual users and the context in which they areworking). Second, many recommendations do notrequire additional resources, but, rather, taking theperspective of stakeholders and transparently reportinginformation likely available from implementation notesof project staff. Some things such as collecting interven-tion costs and sustainability data will require additionalresources or doing things differently. Third, severalrecent funding announcements provide support for amore innovative and integrated approach [e.g., "Inno-vative research methods: Prevention and managementof symptoms in chronic illness" (PAR-13-165); "Systemsscience and health in the behavioral and social science"(PAR-11-314/5) and "Short-term mentored careerenhancement awards in the basic behavioral and socialsciences: Cross-training at the intersection of animalmodels and human investigation" (RFA-DA-14-002);"dissemination and implementation research in health"(PAR-13-055); "Physical activity and weight controlinterventions among cancer survivors: effects on bio-markers of prognosis and survival" (PAR-12-228/9)].

Finally, we assert that the present paradigm of each Tstage, and often each research laboratory, doing thingsin their own silo has been demonstrably ineffective atstimulating translation. If we are serious about makingresearch more broadly applicable and having a popu-lation health impact (45, 46), business as usual will notachieve these goals.

We do not expect every study at every T phase toincorporate all the recommendations in the tables andtext. Incremental progress is needed and will be helpful.However, given the magnitude of the challenges andimportant goal of eventually broadly disseminating effec-tive and sustainable physical activity programs for cancersurvivors, multiple actions are required. Like other usefulguides, such as the chronic caremodel (96, 97) greater andmore rapid progresswill bemade if future research uses amajority of the strategies above in conjunction with eachother, rather than in isolation.

Disclosure of Potential Conflicts of InterestNo potential conflicts of interest were disclosed.

DisclaimerThe opinions expressed are those of the authors and do not necessarily

represent those of the National Cancer Institute.

Authors' ContributionsConception and design: S.M. Phillips, C.M. Alfano, F.M. Perna,R.E. GlasgowDevelopment of methodology: C.M. Alfano, F.M. Perna, S.M. PhillipsWriting, review, and/or revision of the manuscript: S.M. Phillips,C.M. Alfano, F.M. Perna, R.E. GlasgowStudy supervision: S.M. Phillips

The costs of publication of this article were defrayed in part by thepayment of page charges. This article must therefore be hereby markedadvertisement in accordance with 18 U.S.C. Section 1734 solely to indicatethis fact.

Received December 20, 2013; revised February 17, 2014; acceptedFebruary 18, 2014; published OnlineFirst March 5, 2014.

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