ETHICS COMPANION STUDIES: STRATEGIES, SUCCESSES, AND SETBACKS

Transcription

1 ETHICS COMPANION STUDIES: STRATEGIES, SUCCESSES, AND SETBACKS Rebecca D. Pentz, PhD Margie D. Dixon, Research Coordinator Kristopher A. Hendershot, Ethics Fellow

2 Why Would You Include an Ethicist? Rebecca D. Pentz, PhD Clinical and Research Ethics Consultant CLINICAL RESEARCH

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4 RESEARCH ETHICIST: WHAT DOES SHE DO?

5 RESEARCH ETHICIST

6 Mrs. Fix-it Dr Pentz, We now can do next-gen sequencing but none of our consents allows us to do that. Can you fix it? Sincerely, Brilliant Researcher

7 Rescuer Dr. Pentz, We need one more publication for this grant submission to show what a great team we are. Can you finish those interviews you are doing, analyze, and submit in 4 weeks? Sincerely, Great Grant Writer

8 Adapter The Ethics Team is tasked to design Ethics Companion Studies for every major grant submitted by Winship. We also have our agenda. How to mesh the two?

9 Ethics Companion Study: Empirically study an ethics question raised by the design, patient population, or other aspect of the primary study.

10 Embedding a Companion Study in a Grant Ethics writes a short paragraph stating objectives. Saves grant space for the primary study. The complete Ethics Protocol is attached in an appendix. Ethics PI gets 1-5% effort. Ethics research coordinator gets 5-20% effort. Strategy: Gives the grant an attention to ethics without substantial cost.

11 Ethics Companion Studies Companion ethics study is a strength; consent to the research-only biopsy may be a challenge. Grant review by External Advisory Board

12 Success as the Adapters Ethics Team is concerned about Phase I research.

13 Phase 1 Ethical Concerns Patients with no proven treatment options Hope to personally benefit Willing to take risks and discomfort - biopsies Difficult to adequately inform Have a short life expectancy and phase I trial may decrease quality of life.

14 RESPONSE RATES IN PHASE I CANCER TRIALS : 228 Phase I Trials 6.0% Objective Response Complete Response (0.9%) lasted median 6 months Partial response (5.0%) lasted median 3 months DD Huff, J Turner. Response Rates, Duration of Response and Dose Response effects in Phase I Studies of Antineoplastics. Investigational New Drugs. (1991) 9:

15 Newer Phase I Trials: No Adult Data on Benefit New kinds of agents: antibodies, vaccines, antiangiogenesis, molecularly targeted like imatinib mesylate (Gleevec) ( complete response rate of 98% in phase I). Old designs minimize toxicity but also minimize chance of benefit. New trials may use more than one agent.

16 Therapeutic Misconception (TM): Conflating Research and Treatment When participants blur research and therapy (they believe that research is designed specifically for their personal care).

17 Therapeutic Misestimation Overestimating the probability of benefit. Underestimating the probability of risk.

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19 Research Procedures

20 Lung Cancer PO1: PI Fadlo Khuri Included several Phase I trials: RAD001 Phase IB RAD001 Phase I/II

21 Designed a mixed methods empirical study of Phase 1 patients Quantitative: Thinking about the research study you discussed with your physician, is the research study (Please check one answer) a. mostly intending to help you as a person? b. mostly intending to help research and gain knowledge?

22 Mixed Methods: Qualitative What would you say is the main reason you wanted to join this research study? Answer recorded verbatim on interview form by interviewer, code dictionary developed, double coded, third investigator resolved disputes, and major themes identified.

23 Study Population 95/114(83%) Phase I participants: The median age was 57 (range 28-85); 56% males; 67% white; 50% college graduates; 57% incomes > to $60,000. Typical of Phase I participants.

24 Results % understood that phase I research is not standard medical care. Misunderstanding associated with: -less than a college degree (p = 0.008); -family incomes less than $60,000 (p =0.001); -a higher religion score (REL) (p=0.031).

25 Results - 2 Motivation: 76% - direct medical benefit Chance of benefit: >70% (62%) -this estimate is factual 18% -this is what I hope will happen 33% -a positive attitude is important 45% Least frequently identified risk: Risks novel to research, such as non-therapeutic biopsies. Pentz, Cancer 2012

26 Results - Research Biopsies 31% (19/62) understood lack of benefit from research biopsy. Research biopsies considered non-risky (mean score of 3/10). 65% would agree to an optional biopsy. I've had so many, it s no big deal. I hope to help all of us. It is my way of giving back.

27 Subaims Research Biopsies Observed 18 consent conversations: 11 were about trials with research biopsies. Only 27% clearly differentiated research and clinical biopsies. Clear: Unfortunately, for this study, you know that it is an extra biopsy. You don't need to have this biopsy done ordinarily.

28 Subaims Research Biopsies Reviewed all the consents for trials with biopsies (n=28): Only 11% were clear whether the biopsy would help the patient, impact care. Unclear: Careful explanation that the research biopsy would gauge the effect of the study agent on BM but silent about whether impacted patient care. R Pentz, IRB 2012

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30 SO NOW WHAT??

31 Ethics is here to Make a Difference in Clinical Care Improved Consent Form: Embedded in new Lung PO1 submission Integrate Supportive Care: Funded by Winship Values Tool: Funded by Winship

32 Improved Consent Form for Research Biopsy A chart listing whether each procedure: 1. Is being done for research (i.e. would not be done in standard care); 2. Whether the result impacts patient care (e.g. decides treatment). Improved consents have never worked before BUT this one is very targeted.

33 Supportive Care Consult Pilot study to provide Supportive Care Consults to 15 persons on the Phase I Waiting List. Hypothesis: Patients will more seriously consider alternatives to Phase I postsupportive care consult.

34 Values Tool Patients check their top 4 of 16 priorities at this point in their care: Spending more time at home with my family than in the clinic Having access to new treatments, even if they are not yet proven and are part of research

35 Values Tool Goal Help physicians differentiate patients who value Phase I participation from those who do not.

36 OTHER ETHICS COMPANION STUDIES

37 Head and Neck SPORE Primary Study: Chemoprevention study with a natural compound. Ethics Companion: Explore communication about and usage of CAM. Result: Found lack of communication and no standard lexicon of CAM terms.

38 H&N Spore Deliverable Grant renewal: Ethics will interview participants and produce a standardized lay language CAM lexicon.

39 Breast SPORE: Primary study does whole genome and epigenome sequencing. Patient understanding of genetic testing poor.

40 Breast SPORE Companion study: (1) Conduct mixedmethod interviews to identify knowledge gaps and concerns; (2) Design a one-page educational tool using the words of the patients to inform future patients. Deliverable: Genetic Educational Tool

41 Setbacks: Phase 0 Trial part of SPORE

42 Phase 0 Trials Intended to make drug development speedier, more efficient, and cost effective. Less pre-clinical data needed: Two animal species only. Compounds do not need to be GMP quality or produced in large quantities.

43 SPORE Phase 0 Which curcumin analog is most promising?

44 Ethical Concerns: Phase 0 No possibility of benefit to patient. Trial has: Two biopsies Day 0 and Day 8; Blood draws Day 0, 1, 3, 8. No possibility to continue if patient thinks he/she feels better.

45 DESIGNED A STUDY TO ASSESS MOTIVATION AND UNDERSTANDING

46 Curcumin Analogs Were Too Toxic

47 Exception from Informed Consent for Emergency Research LURED BEYOND CANCER

48 Ethicist for the ProTECT Study Closed head traumatic brain injury study. Can t consent participants. Use FDA s EFIC rules. Ethics Team helping fulfill EFIC rules.

49 Two Companion Studies Studying the required Community Consultation: Comparing the pros and cons of each CC method. Interviewing actual participants after the trial about their understanding and attitude toward being included.

50 Why Do Ethics Companion Studies? Embedding ethics companion studies contributes to ethics research to improve patient care.

51 Why Do Ethics Companion Studies? The Winship Ethics Team is producing: Improved research biopsy consent; Integration of Supportive Care; Values Tool; CAM lay lexicon; Genetic testing educational material.

52 DISCUSSION AND QUESTIONS