Ethical Considerations for Vaccine Research

Transcription

1 Ethical Considerations for Vaccine Research Leila C. Sahni, MPH Immunization Project Texas Children s Hospital September 28, 2012 Texas Immunization Summit 2012

2 Objectives for Participants 1. Understand the ethical considerations associated with vaccine research and studies involving children; 2. Identify the common study designs proposed by antivaccine groups and describe the associated flaws; 3. Describe ideal vaccine research study designs and understand why these designs are or are not feasible.

3 Ethics What are they? What do they have to do with research? Why do they matter?

4 The Nuremberg Trials Often, in those difficult hours in camp, I had been sustained by the faith that there would be a day when those responsible for this regime would be called before the bar. This faith gave me the strength to keep going. Today this day is here. Ernst Michel Former Prisoner Number 104,995

5 The Tuskegee Syphilis Experiment

6 STD Research in Guatemala Ethically Impossible: STD Research in Guatemala from 1946 to 1948

7 The Nuremberg Code 1. Voluntary consent 2. Societal benefits 3. Uses prior knowledge 4. No unnecessary suffering 5. No risk of death or disabling injury 6. Risk from participation less than value of results 7. Protection from injury, disability, death 8. Conducted by scientifically qualified investigators 9. Withdrawal at any time 10. Termination by investigators at any time if probable cause

8 How has this Impacted Research Today? Creation of Institutional Review Boards Development of ethics committees Declaration of conflicts of interest Implementation of peer-review process

9 Question 1 A physician wants to collect blood samples from healthy children for use in a study comparing blood markers in autistic and non-autistic children. He proposes recruiting the healthy children at his son s birthday party. Given that he is only recruiting 20 children, he determines that IRB approval is not needed. After obtaining verbal parental permission, he will pay each child $10 for participating. Should this research have been reviewed by an IRB?

10 Text your response to Yes: No: I don t know: 63891

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12 What is an Institutional Review Board? Composed of MDs, PhDs, ethicists, lay persons Reviews all research involving human subjects Ensures the protection of human subjects Special protection for vulnerable populations Evaluates risks and benefits of proposed study

13 IRB Considerations Informed Consent Risk:Benefit Meaningful Contribution Ethical Oversight

14 Question 2 A physician wants to collect blood samples from healthy children for use in a study comparing blood markers in autistic and non-autistic children. He proposes recruiting the healthy children at his son s birthday party. The protocol has been reviewed and approved by his institution s IRB. After obtaining verbal parental permission, he will pay each child $10 for participating. Is verbal parental permission adequate?

15 Text your response to Yes: No: I don t know: 64010

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17 What Constitutes Informed Consent? Informed Consent Procedures, risks, and benefits are explained in ageappropriate, lay language Participants questions are answered Written documentation (few exceptions) Parent/guardian consents for minor < 18 years; children 7 years must assent

18 Question 3 A physician wants to collect blood samples from healthy children for use in a study comparing blood markers in autistic and non-autistic children. He proposes recruiting the healthy children at his son s birthday party. The protocol has been reviewed and approved by his institution s IRB. After obtaining verbal parental permission, he will pay each child $10 for participating. Is the risk to the children minimal?

19 Text your response to Yes: No: I don t know: 64022

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21 Risk-Benefit Ratio Risk:Benefit Evaluation of risk-benefit ratio is a major responsibility of the IRB Are the risks to subjects justified by the anticipated benefits to the individual or society? Includes physical, economic, and psychological risks Minimal risk commonly used research standard

22 Question 4 A physician wants to collect blood samples from healthy children for use in a study comparing blood markers in autistic and non-autistic children. He proposes recruiting the healthy children at his son s birthday party. The protocol has been reviewed and approved by his institution s IRB. After obtaining verbal parental permission, he will pay each child $10 for participating. Was it ok to do this at a children s birthday party?

23 Text your response to Yes: No: I don t know: 64073

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25 Ethical Oversight and Vulnerable Populations Ethical Oversight Additional safeguards for subjects particularly vulnerable to coercion Children, prisoners, pregnant women, mental illness Essential that subjects have the capacity to consent Research involving prisoners and children highly regulated; most restricted to minimal risk category

26 Question 5 A physician wants to collect blood samples from healthy children for use in a study comparing blood markers in autistic and non-autistic children. He proposes recruiting the healthy children at his son s birthday party. The protocol has been reviewed and approved by his institution s IRB. After obtaining verbal parental permission, he will pay each child $10 for participating. Is this a meaningful contribution to knowledge about autism?

27 Text your response to Yes: No: I don t know: 64058

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29 Meaningful Contribution to Existing Knowledge Meaningful Contribution Somewhat subjective; dependent on knowledge of the field Research may appear meaningful, but not the case if study has already been conducted Is the study adequately designed to evaluate its research question?

30 Basic research principles Power and sample size Randomization Bias and confounding

31 Power and Sample Size Power: the ability of the study to detect a difference in 2 groups. Expressed as a probability or percentage; usually 80% or 90% Sample size: the number of people needed in each group to describe the characteristics of the group and detect a difference between the two, if one exists

32 Randomization Subjects are assigned to study groups by chance; assignment is unpredictable and characteristics are distributed equally

33 Bias A systematic error in the design or analysis of a study that results in a mistaken estimate of the risk of disease Selection bias: Differences between people who agree and do not agree to participate in a study Differences between people in each of the study groups

34 Confounding Confounding: the relationship between the outcome and factor of interest is obscured by another factor that is related to both the outcome and the first factor

35 Studies requested by the anti-vaccine movement What do they want? Why are they not appropriate?

36 IOM: Assessment of Health Outcomes and the Immunization Schedule Comparison of health outcomes in children who followed ACIP schedule and those who did not Identification of research approaches, study design, and methodologies Important to consider end points, herd immunity, indirect effects Barbara Loe Fisher Courtesy of NVIC

37 Study 1: Prospective Study of Pregnant Women Voluntary participation of pregnant women enrolled in their first trimester Participants choose vaccination schedule for their children Morbidity and mortality outcomes compared across exposure groups Analysis at 6 and 15 years Is this a strong study design? Proposed by Barbara Loe Fisher, IOM meeting, February 2012, Washington, DC

38 Text your response to Yes: No: I don t know: 64083

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40 Study 2: Prospective Randomized Trial in Primates Prospective, randomized control trial conducted in non-human primates Vaccination schedule randomly assigned Morbidity, mortality, and overall health assessed at predetermined endpoints Outcomes compared across groups at the end of the study Is this a strong study design? Proposed by Barbara Loe Fisher, IOM meeting, February 2012, Washington, DC

41 Text your response to Yes: No: I don t know: 64094

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43 Study 3: Retrospective Study of Mothers and Children Voluntary participation of mothers and children Occurs after initiation of vaccination Group women and children by vaccination schedule and compare health outcomes among children Statistical controls used to adjust for potential confounders Is this a strong study design? Proposed by Barbara Loe Fisher, IOM meeting, February 2012, Washington, DC

44 Text your response to Yes: No: I don t know: 64105

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46 Study 4: Retrospective Study Among Children who Received VCIP Compensation Children who received VCIP compensation are compared to their siblings who followed an alternative schedule Frequency and severity of health outcomes in the two groups are compared Is this a strong study design? Proposed by Barbara Loe Fisher, IOM meeting, February 2012, Washington, DC

47 Text your response to Yes: No: I don t know: 64121

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49 So, What Does the Ideal Study Look Like? Assesses indirect effects of vaccination (herd immunity); doesn t just examine results among vaccinated or unvaccinated Children randomly assigned to vaccine schedule; those who receive no vaccines are given placebo Is this study possible?

50 Text your response to Yes: No: I don t know:

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52 Possible Approaches Use of post-marking databases (VAERS, VSD, CISA, PRISM) Retrospective reviews of electronic medical records and health insurance claims data Different approaches for acute and lateonset adverse events Most involve statistical modeling or retrospective designs Stay tuned; final report expected by the end of this year

53 Leila C. Sahni, MPH (832)