1 / 64

RECRUITMENT, ADHERENCE, AND RETENTION STRATEGIES TALES FROM CLINICAL TRIALS

RECRUITMENT, ADHERENCE, AND RETENTION STRATEGIES TALES FROM CLINICAL TRIALS. Kelley R. Branch, MD, MSc, FACC Associate Director, Clinical Trials Services Unit Medical Director, CCU/5NE. A Clinical Trial Story…. Once upon a time, there were 4 hypertension trials….

gavan
Download Presentation

RECRUITMENT, ADHERENCE, AND RETENTION STRATEGIES TALES FROM CLINICAL TRIALS

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. RECRUITMENT, ADHERENCE, AND RETENTION STRATEGIESTALES FROM CLINICAL TRIALS Kelley R. Branch, MD, MSc, FACC Associate Director, Clinical Trials Services Unit Medical Director, CCU/5NE

  2. A Clinical Trial Story… Once upon a time, there were 4 hypertension trials…

  3. COMPARISON OF SHEP, STOP-H, MRC-92 AND SYST-EUR CHARACTERISTICS

  4. Sys-Eur Trial: Accrual

  5. Trial Adherence

  6. SYST - EURA WORST CASE ANALYSIS? Late Recruitment = Fewer Events High Lost to Follow Up = No Definitive Conclusions from the Trial

  7. Major Trial Issues • Recruitment - Timely Enrollment • Adherence • Complete Follow Up

  8. RECRUITMENT MANTRA: “Get Sufficient Population In a Reasonable Time”

  9. RECRUITMENTFUNDAMENTAL POINT Successful recruitment depends on developing a careful plan with multiple strategies, maintaining flexibility, establishing interim goals and preparing to devote the necessary effort. Friedman, Furberg and DeMets

  10. RECRUITMENT • Successful recruitment has been documented in many trials • Clinical Sites: Past performance predicts future • Centers carefully selected by past performance (http://www.fhcrc.org/science/phs/swog/recrcct/)

  11. RECRUITMENT:BASIC ISSUES • Planning • Sources and support • Strategies • Conduct - Implementation • Monitoring - Short and long term goals • Problems - Expect them to happen • Solutions - Make them occur • Have reasons for participation

  12. RECRUITMENT: CAREFUL PLANNING • BE CONSERVATIVE IN YOUR ESTIMATES • Design easy recruitment • Establish interim goals • Have contingency plans • 3 TO 6 MONTH PERIOD TO SEE RESULTS

  13. TRIAL PLANNING • Increase likelihood of getting sufficient participants • Staff – Organized, experienced • Institutional support - proper facilities • Publicity - start before trial • Multiple recruitment strategies - at least 3 • Pilot test strategies • Contingency plans • Statistical power - assumes constant enrollment

  14. ADVANTAGES: WIDE ENTRY CRITERIA • Easier screening and recruitment • More feasible and affordable • Broader range of variables and larger study size • Reliable overall result • Greater public health impact • Testing subgroup hypotheses

  15. RECRUITMENT DATA: Variable Success in 13 NHLBI Studies

  16. SELECT Trial AccrualProjected and Actual Projected

  17. ACCORD Initial Trial

  18. ACCORD Main Trial Accrual

  19. RECRUITMENT STRATEGIES (N=3)How to Get Patients Chart Review Websites Media Efforts Registries Direct Mail Blood Bank Donors Mass Screening Occupational Screening Laboratory Lists Medical Referrals

  20. Checklist: OVERALL RECRUITMENT PROGRAM • Start recruitment on target date • Choose physically accessible location • Use at least three recruitment strategies • Recruitment Coordinator - overall responsibility • Trial-wide recruitment coordinator network • Accurate tracking system • Match staff and screenees

  21. OVERALL RECRUITMENT PROGRAM • Provide staff back-up • Be aware and anticipate staff burnout • Inform medical and lay communities • Recruits - Solicit in simple language • Medical associations and hospital staffs - contacted by the Principal Investigator

  22. OVERALL RECRUITMENT PROGRAM • Identify excellent, experienced staff • Calendar for ENTIRE recruitment period • Pretest your recruitment strategies • Regular review and evaluation of program • Develop contingency plans • Flexible clinic hours

  23. PATIENT REASONS FOR PARTICIPATION • Answer scientific question accurately • Altrusim: Benefit other patients - current and future • Benefit to themselves • additional monitoring • second opinion of their condition • reassurance regarding diagnosis

  24. RECRUITMENT OF STUDY POPULATION RECRUITMENT FAILURE CAUSES: • Late start • Inadequate planning • Insufficient effort • Overly optimistic expectations MANTRA: “Get Sufficient Population In a Reasonable Time”

  25. POTENTIAL PROBLEMSExpect them-they will occur • Inadequate funding for screening process • Unwillingness to refer or allow participation • Overestimation of prevalence • Overly rigorous entry criteria

  26. POSSIBLE RECRUITMENT SOLUTIONS • EXTEND THE TIME FOR ENROLLMENT-X? • RELAX INCLUSION/EXCLUSION CRITERIA-X • ACCEPT A SMALLER SAMPLE SIZE-X • RECYCLE PREVIOUS INELIGIBLES-O • CHANGE THE DESIGN-XXX

  27. Recruitment: Summary • Plan, plan, plan • Design for success with recruitment program • At least 3 recruitment strategies • Problems happen • Sufficient population in reasonable time

  28. Clinical TrialsADHERENCE

  29. ADHERENCE DEFINITION Adherence is the extent to which a person’s behavior coincides with medical or health advice in terms of taking medications, following diets, using devices, or executing life-style changes.

  30. TERMINOLOGY: ADHERENCE VS. COMPLIANCE • Adherence is preferred term • Adherence: Active, choice, interactive • Compliance: Passive, non-selective NHLBI Workshop, Bethesda, MD 1987

  31. OVERALL ADHERENCE PLAN • Develop a bottom line - cannot be transgressed • Minimum amount of data which is essential • Set adherence goals depending on protocol • “Acceptability” trial • “Alteration of natural history” trial • Teach adherence techniques, plan for poor adherence • Run-in and test dosing procedures • Have a maintenance plan for everyone

  32. BOTTOM LINE:MINIMUM ACCEPTABLE ADHERENCE • Know primary outcome status on every randomized participant. • Human behavior will allow few to purposely harm a worthy scientific project.

  33. Adherence is bad in clinical trials. Get over it.

  34. SAMPLE SIZE ADJUSTMENT FOR REDUCED ADHERENCE • Key Point - Adherence correction term-sample size formula, a squared function. 2N = 2(z + z)2  (1 - 2)2(1-p)2 p = Reduction in Adherence pSS Increase .01 1.02 .05 1.11 .10 1.23 .20 1.56 .30 2.04 .50 4.00 MRC

  35. “ALTERATION OF NATURAL HISTORY” TRIAL • Enrolled group must do the intervention • Looking for efficacy on clinical outcomes • Adherence is crucial • e.g., Phase IV trials

  36. LRC: ANALYSIS FOR PREDICTORS OF ADHERENCE Adherence after first month associated with: • Adherence in first month- most powerful predictor (r=.59 or r²=.34) • r²=.36 with smoking and other factors added • Smoking status • Age • Extent of Psychological Distress • No statistical association with: • Exercise -Overall risk status • Weight -Motivational level • Vitamin consumption

  37. FACTORS AFFECTING ADHERENCE TO INTERVENTIONS

  38. “RUN-IN” PERIOD • Pre-randomization procedure • Single blind • Placebo used • Stress test for "pill-taking behavior”

  39. CONCLUSIONS ABOUT “PLACEBO RUN-IN PERIOD” What does it do • Identifies a group of individuals who don’t adhere well during designated run-in • Successful repeat run-in performers (6.9%) adhere less well during trial • Those identified representative of those enrolled What doesn’t it do • Identify all who will adhere poorly to intervention Uncertainties • If those who “fail” would all be poor adherers • Cost/Benefit-advantageous

  40. “TEST-DOSING” PERIOD • Pre-randomization procedure • Single blind • Active drug used • Identify those with severe adverse effects

  41. Non-Adherence

  42. SIGNS OF POTENTIAL NON-ADHERENCE: “RED FLAGS” • Missed visits • Difficulty in reaching by phone or failure to return calls • Rescheduling appointment twice (change in behavior) • Complaints about office visits • Impatience during clinic visit • Length of time (mandatory) at each visit • “Distance” during interview • Length of time since participation in study was discussed between physician and participant • Humor dealing with negative aspects of trial medication

  43. SIGNS OF POTENTIAL NON-ADHERENCE: “RED FLAGS” • Sarcasm about trial or study medication • Any expression by participant that he/she may discontinue study medication • Unusual or unexplained change in adherence to study medication • Unconcern by participant about adherence rate • Reassignment to new primary-care manager • Reassignment to other new clinic personnel • Illness with increased attention to “trial related disease” • Hospitalization for any reason • Any major change in life style which is imminent

  44. DISTRIBUTION OF ADHERENCE PROBLEMS IN A CADRE OF DROPOUTS AND OTHERS IN AN RCT

  45. MECHANISMS INVOLVED IN PARTICIPANT NON-ADHERENCE • Lack motivation • Lack of knowledge (disease, intervention) • Rejects medical diagnosis • Denies significance of disease process • Self-debate over intervention regimen • Rejects intervention regimen

  46. Psychologist-Behaviorist Nurse-Clinician Therapeutic Plan Participant(Patient) Intervention Schedule PhysicianAssistant Physician Dietitian-Nutritionist MEDICAL THERAPEUTICS TEAM

  47. PRINCIPLES AND GOALS: PARTICIPANT COUNSELING IN DROPOUT RECOVERY

  48. RECOVERY OF DROPOUTS BAYLOR-METHODIST CLINIC OF CPPT • 94 % were recovered for some regular visit with clinic personnel (90% within 6 months ) • Remaining participant was contacted regularly by telephone • 3% recidivism • 70% reinstituted study medication • Average adherence: study medication 35 %

More Related