Skip to main content
SpringerLink
Log in

Prevention Trials: Challenges in Design, Analysis, and Interpretation of Prevention Trials

  • Living reference work entry
  • First Online:
Principles and Practice of Clinical Trials

  • 76 Accesses

Abstract

Designing a prevention trial requires understanding the natural history of the disease, and the likely length of intervention required to achieve a reduction in incidence. The population suitable to contribute meaningful information to the outcomes under study, the intervention is appropriate and likely will generate a balance of risks and benefits for the typically disease free population, and the primary outcome is biologically plausible and clinically relevant. Given the relatively long evolution of chronic diseases, prevention trials bring extra pressures on two fundamental issues in the design of the trial: adherence to the preventive intervention among participants who are otherwise healthy, and sustained follow-up of trial participants. With growing emphasis on the composition of the trial participant population reflecting the overall population for ultimate application of the results, there is the need for additional attention to recruitment and retention of participants. This is fundamental to planning a prevention trial. Planning for follow-up after the intervention is completed helps place the intervention and outcomes in the context of the disease process but adds complexity to recruitment. Never the less this adds to insights from prevention trials. Improving risk stratification for identification of eligible participants for recruitment to prevention trials can improve efficiency of the trials and fit prevention trials in the context of precision prevention.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Alberts DS, Martinez ME, Roe DJ, Guillen-Rodriguez JM, Marshall JR, van Leeuwen JB, Reid ME, Ritenbaugh C, Vargas PA, Bhattacharyya AB, Earnest DL, Sampliner RE (2000) Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians’ Network. N Engl J Med 342(16):1156–1162. https://doi.org/10.1056/NEJM200004203421602

    Article  Google Scholar 

  • Blot WJ, Li JY, Taylor PR, Guo W, Dawsey S, Wang GQ, Yang CS, Zheng SF, Gail M, Li GY et al (1993) Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 85(18):1483–1492. https://doi.org/10.1093/jnci/85.18.1483

    Article  Google Scholar 

  • Cairns J, Cohen L, Colton T, DeMets DL, Deykin D, Friedman L, Greenwald P, Hutchison GB, Rosner B (1991) Issues in the early termination of the aspirin component of the Physicians’ Health Study. Data Monitoring Board of the Physicians’ Health Study. Ann Epidemiol 1(5):395–405. https://doi.org/10.1016/1047-2797(91)90009-2

    Article  Google Scholar 

  • Chen MS Jr, Lara PN, Dang JH, Paterniti DA, Kelly K (2014) Twenty years post-NIH Revitalization Act: enhancing minority participation in clinical trials (EMPaCT): laying the groundwork for improving minority clinical trial accrual: renewing the case for enhancing minority participation in cancer clinical trials. Cancer 120(Suppl 7):1091–1096. https://doi.org/10.1002/cncr.28575

    Article  Google Scholar 

  • Chen WY, Rosner B, Colditz GA (2007) Moving forward with breast cancer prevention. Cancer 109(12):2387–2391. https://doi.org/10.1002/cncr.22711

    Article  Google Scholar 

  • Cook NR, Cole SR, Hennekens CH (2002) Use of a marginal structural model to determine the effect of aspirin on cardiovascular mortality in the Physicians’ Health Study. Am J Epidemiol 155(11):1045–1053. https://doi.org/10.1093/aje/155.11.1045

    Article  Google Scholar 

  • Cuzick J (2010) Long-term follow-up in cancer prevention trials (it ain’t over ‘til it’s over). Cancer Prev Res 3(6):689–691. https://doi.org/10.1158/1940-6207.CAPR-10-0096

    Article  Google Scholar 

  • DeCensi A, Puntoni M, Guerrieri-Gonzaga A, Caviglia S, Avino F, Cortesi L, Taverniti C, Pacquola MG, Falcini F, Gulisano M, Digennaro M, Cariello A, Cagossi K, Pinotti G, Lazzeroni M, Serrano D, Branchi D, Campora S, Petrera M, Buttiron Webber T, Boni L, Bonanni B (2019) Randomized placebo controlled trial of low-dose tamoxifen to prevent local and contralateral recurrence in breast intraepithelial neoplasia. J Clin Oncol 37(19):1629–1637. https://doi.org/10.1200/JCO.18.01779

    Article  Google Scholar 

  • Eriksson M, Eklund M, Borgquist S, Hellgren R, Margolin S, Thoren L, Rosendahl A, Lang K, Tapia J, Backlund M, Discacciati A, Crippa A, Gabrielson M, Hammarstrom M, Wengstrom Y, Czene K, Hall P (2021) Low-dose tamoxifen for mammographic density reduction: a randomized controlled trial. J Clin Oncol 2021:JCO2002598. https://doi.org/10.1200/JCO.20.02598

    Article  Google Scholar 

  • Fisher B, Costantino J, Wickerham D, Redmond C, Kavanah M, Cronin W, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N, Other National Surgical Adjuvant Breast and Bowel Project Investigators (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 90:1371–1388

    Article  Google Scholar 

  • Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, Robidoux A, Bevers TB, Kavanah MT, Atkins JN, Margolese RG, Runowicz CD, James JM, Ford LG, Wolmark N (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 97(22):1652–1662

    Article  Google Scholar 

  • Glynn RJ, Buring JE, Manson JE, LaMotte F, Hennekens CH (1994) Adherence to aspirin in the prevention of myocardial infarction. The Physicians’ Health Study. Arch Intern Med 154(23):2649–2657. https://doi.org/10.1001/archinte.1994.00420230032005

    Article  Google Scholar 

  • Grau MV, Baron JA, Sandler RS, Wallace K, Haile RW, Church TR, Beck GJ, Summers RW, Barry EL, Cole BF, Snover DC, Rothstein R, Mandel JS (2007) Prolonged effect of calcium supplementation on risk of colorectal adenomas in a randomized trial. J Natl Cancer Inst 99(2):129–136

    Article  Google Scholar 

  • Greenwald P, Anderson D, Nelson SA, Taylor PR (2007) Clinical trials of vitamin and mineral supplements for cancer prevention. Am J Clin Nutr 85(1):314S–317S

    Article  Google Scholar 

  • Jaffee EM, Dang CV, Agus DB, Alexander BM, Anderson KC, Ashworth A, Barker AD, Bastani R, Bhatia S, Bluestone JA, Brawley O, Butte AJ, Coit DG, Davidson NE, Davis M, DePinho RA, Diasio RB, Draetta G, Frazier AL, Futreal A, Gambhir SS, Ganz PA, Garraway L, Gerson S, Gupta S, Heath J, Hoffman RI, Hudis C, Hughes-Halbert C, Ibrahim R, Jadvar H, Kavanagh B, Kittles R, Le QT, Lippman SM, Mankoff D, Mardis ER, Mayer DK, McMasters K, Meropol NJ, Mitchell B, Naredi P, Ornish D, Pawlik TM, Peppercorn J, Pomper MG, Raghavan D, Ritchie C, Schwarz SW, Sullivan R, Wahl R, Wolchok JD, Wong SL, Yung A (2017) Future cancer research priorities in the USA: a Lancet Oncology Commission. Lancet Oncol 18(11):e653–e706. https://doi.org/10.1016/S1470-2045(17)30698-8

    Article  Google Scholar 

  • Klein WM, Stefanek ME (2007) Cancer risk elicitation and communication: lessons from the psychology of risk perception. CA Cancer J Clin 57(3):147–167. https://doi.org/10.3322/canjclin.57.3.147

    Article  Google Scholar 

  • Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM, Diabetes Prevention Program Research Group (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346(6):393–403. https://doi.org/10.1056/NEJMoa012512

    Article  Google Scholar 

  • Limburg PJ, Wei W, Ahnen DJ, Qiao Y, Hawk ET, Wang G, Giffen CA, Wang G, Roth MJ, Lu N, Korn EL, Ma Y, Caldwell KL, Dong Z, Taylor PR, Dawsey SM (2005) Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib. Gastroenterology 129(3):863–873

    Article  Google Scholar 

  • Martinez ME, Marshall JR, Giovannucci E (2008) Diet and cancer prevention: the roles of observation and experimentation. Nat Rev Cancer 8(9):694–703

    Article  Google Scholar 

  • Martino S, Cauley JA, Barrett-Connor E, Powles TJ, Mershon J, Disch D, Secrest RJ, Cummings SR (2004) Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 96(23):1751–1761

    Article  Google Scholar 

  • Matheny M, Israni S, Ahmed M, Whicher D (2019) Artificial intelligence in health care: the hope, the hype, the promise, the peril, NAM special publication. National Academy of Medicine, Washington, DC

    Google Scholar 

  • Moons KG, Kengne AP, Grobbee DE, Royston P, Vergouwe Y, Altman DG, Woodward M (2012a) Risk prediction models: II. External validation, model updating, and impact assessment. Heart 98(9):691–698. https://doi.org/10.1136/heartjnl-2011-301247

    Article  Google Scholar 

  • Moons KG, Kengne AP, Woodward M, Royston P, Vergouwe Y, Altman DG, Grobbee DE (2012b) Risk prediction models: I. Development, internal validation, and assessing the incremental value of a new (bio)marker. Heart 98(9):683–690. https://doi.org/10.1136/heartjnl-2011-301246

    Article  Google Scholar 

  • Parker-Pope T (2007) Do pills have a place in cancer prevention? Wall Street J 2007:D1

    Google Scholar 

  • Peto R, Gray R, Collins R, Wheatley K, Hennekens C, Jamrozik K, Warlow C, Hafner B, Thompson E, Norton S et al (1988) Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J 296(6618):313–316. https://doi.org/10.1136/bmj.296.6618.313

    Article  Google Scholar 

  • Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, Margolis KL, Limacher MC, Manson JE, Parker LM, Paskett E, Phillips L, Robbins J, Rossouw JE, Sarto GE, Shikany JM, Stefanick ML, Thomson CA, Van Horn L, Vitolins MZ, Wactawski-Wende J, Wallace RB, Wassertheil-Smoller S, Whitlock E, Yano K, Adams-Campbell L, Anderson GL, Assaf AR, Beresford SA, Black HR, Brunner RL, Brzyski RG, Ford L, Gass M, Hays J, Heber D, Heiss G, Hendrix SL, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Kotchen JM, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Henderson MM (2006) Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295(6):629–642

    Article  Google Scholar 

  • Qiao YL, Dawsey SM, Kamangar F, Fan JH, Abnet CC, Sun XD, Johnson LL, Gail MH, Dong ZW, Yu B, Mark SD, Taylor PR (2009) Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial. J Natl Cancer Inst 101(7):507–518

    Article  Google Scholar 

  • Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288(3):321–333

    Article  Google Scholar 

  • Sargent DJ, Conley BA, Allegra C, Collette L (2005) Clinical trial designs for predictive marker validation in cancer treatment trials. J Clin Oncol 23(9):2020–2027

    Article  Google Scholar 

  • Schatzkin A, Lanza E, Corle D, Lance P, Iber F, Caan B, Shike M, Weissfeld J, Burt R, Cooper MR, Kikendall JW, Cahill J (2000) Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. N Engl J Med 342(16):1149–1155. https://doi.org/10.1056/NEJM200004203421601

    Article  Google Scholar 

  • Shapiro S, Venet W, Strax P, Venet L, Roeser R (1985) Selection, follow-up, and analysis in the Health Insurance Plan Study: a randomized trial with breast cancer screening. Natl Cancer Inst Monogr 67:65–74

    Google Scholar 

  • Steering Committee of the Physicians’ Health Study Research Group (1988) Preliminary report: findings from the aspirin component of the ongoing Physicians’ Health Study. N Engl J Med 318(4):262–264. https://doi.org/10.1056/NEJM198801283180431

    Article  Google Scholar 

  • Steyerberg EW (2009) Clinical prediction models. A practical approach to development, validation, and updating, Statistics for biology and health. Springer, New York. https://doi.org/10.1007/978-0-387-77244-8

    Book  MATH  Google Scholar 

  • Stoll CRT, Izadi S, Fowler S, Philpott-Streiff S, Green P, Suls J, Winter AC, Colditz GA (2019) Multimorbidity in randomized controlled trials of behavioral interventions: a systematic review. Health Psychol 38(9):831–839. https://doi.org/10.1037/hea0000726

    Article  Google Scholar 

  • Tanvetyanon T, Bepler G (2008) Beta-carotene in multivitamins and the possible risk of lung cancer among smokers versus former smokers: a meta-analysis and evaluation of national brands. Cancer 113(1):150–157. https://doi.org/10.1002/cncr.23527

    Article  Google Scholar 

  • The Diabetes Prevention Program Research Group (1999) The Diabetes Prevention Program. Design and methods for a clinical trial in the prevention of type 2 diabetes. Diabetes Care 22(4):623–634. https://doi.org/10.2337/diacare.22.4.623

    Article  Google Scholar 

  • The Lancet (2007) NCI and the STELLAR trial. Lancet 369(9580):2134. https://doi.org/10.1016/S0140-6736(07)60987-8

    Article  Google Scholar 

  • US Food and Drug Administration (2021) Table of surrogate endpoints that were the basis of drug approval or licensure. https://www.fda.gov/drugs/development-resources/table-surrogate-endpoints-were-basis-drug-approval-or-licensure

  • Ware JH (2003) Interpreting incomplete data in studies of diet and weight loss. N Engl J Med 348(21):2136–2137. https://doi.org/10.1056/NEJMe030054

    Article  Google Scholar 

  • Ware JH, Hamel MB (2011) Pragmatic trials – guides to better patient care? N Engl J Med 364(18):1685–1687. https://doi.org/10.1056/NEJMp1103502

    Article  Google Scholar 

  • Warner ET, Glasgow RE, Emmons KM, Bennett GG, Askew S, Rosner B, Colditz GA (2013) Recruitment and retention of participants in a pragmatic randomized intervention trial at three community health clinics: results and lessons learned. BMC Public Health 13:192. https://doi.org/10.1186/1471-2458-13-192

    Article  Google Scholar 

  • Wolin KY, Steinberg DM, Lane IB, Askew S, Greaney ML, Colditz GA, Bennett GG (2015) Engagement with eHealth self-monitoring in a primary care-based weight management intervention. PLoS One 10(10):e0140455. https://doi.org/10.1371/journal.pone.0140455

    Article  Google Scholar 

  • Writing Group (1979) Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA 242(23):2562–2571

    Article  Google Scholar 

  • Writing Group (1998) Design of the Women’s Health Initiative clinical trial and observational study. The Women’s Health Initiative Study Group. Control Clin Trials 19(1):61–109. https://doi.org/10.1016/s0197-2456(97)00078-0

  • Yach D, Hawkes C, Gould CL, Hofman KJ (2004) The global burden of chronic diseases: overcoming impediments to prevention and control. JAMA 291(21):2616–2622. https://doi.org/10.1001/jama.291.21.2616

  • Yusuf S, Joseph P, Dans A, Gao P, Teo K, Xavier D, Lopez-Jaramillo P, Yusoff K, Santoso A, Gamra H, Talukder S, Christou C, Girish P, Yeates K, Xavier F, Dagenais G, Rocha C, McCready T, Tyrwhitt J, Bosch J, Pais P, International Polycap Study 3 Investigators (2021) Polypill with or without aspirin in persons without cardiovascular disease. N Engl J Med 384(3):216–228. https://doi.org/10.1056/NEJMoa2028220

  • Zelen M (1988) Are primary cancer prevention trials feasible? J Natl Cancer Inst 80:1442–1444

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Saint Louis, MO, USA

    Shu Jiang & Graham A. Colditz

Authors
  1. Shu Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Graham A. Colditz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Graham A. Colditz .

Editor information

Editors and Affiliations

  1. Samuel Oschin Comprehensive Cancer Insti, WEST HOLLYWOOD, CA, USA

    Steven Piantadosi

  2. Bloomberg School of Public Health, Johns Hopkins Center for Clinical Trials Bloomberg School of Public Health, Baltimore, MD, USA

    Curtis L. Meinert

Section Editor information

  1. Statistician, MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK

    Babak Choodari-Oskooei

  2. MRC Clinical Trials Unit and Institute of Clinical Trials and Methodology, University College of London, London, England

    Mahesh Parmar

  3. The Johns Hopkins Center for Clinical Trials and Evidence Synthesis, Johns Hopkins School of Public Health, Baltimore, MA, USA

    Curtis L. Meinert

  4. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Steven Piantadosi

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Jiang, S., Colditz, G.A. (2021). Prevention Trials: Challenges in Design, Analysis, and Interpretation of Prevention Trials. In: Piantadosi, S., Meinert, C.L. (eds) Principles and Practice of Clinical Trials. Springer, Cham. https://doi.org/10.1007/978-3-319-52677-5_96-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-52677-5_96-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-52677-5

  • Online ISBN: 978-3-319-52677-5

  • eBook Packages: Springer Reference MathematicsReference Module Computer Science and Engineering

Publish with us

Policies and ethics

Search

Navigation