Facing Up The Challenge Sep 27 2007

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Facing Up The Challenge Sep 27 2007

  1. 1. Facing Up to the Challenge Informed Consent in Vulnerable Populations
  2. 2. Vulnerable populations <ul><li>ICH definition: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation {…}. </li></ul>
  3. 3. Not to harm <ul><li>Subjects who are vulnerable should not be exposed to interventions involving more than minimal risks. </li></ul>
  4. 4. Delimiting the problem <ul><li>Science should never consider human beings as an instrument to be employed for scientific purposes. </li></ul><ul><li>With the advancing technology of medicine, rights of the society as a whole and those of the individual are frequently in conflict. </li></ul>
  5. 5. Good of many or respect of the few? <ul><li>There is now a dual focus to do on groups AND on individuals </li></ul><ul><li>Moral principles cross one another; which principles/values should take priority? </li></ul>
  6. 6. Quest for justice? <ul><li>Shift in perception regarding participation in research </li></ul><ul><li>Burden requiring protection </li></ul><ul><li>↓ </li></ul><ul><li>Benefits to be sought </li></ul>
  7. 7. Timeline concept of protection <ul><li>People who cannot protect themselves should be protected by society. </li></ul>
  8. 8. Current challenge <ul><li>Are we putting excessive obstacles in the way of needed and legitimate research activities? </li></ul>
  9. 9. Protective concept of justice <ul><li>Requirement of individual informed consent to medical experimentation </li></ul>
  10. 10. Protective concept of justice (continued) <ul><li>Requirement that IRBs/ECs review research protocols, to ensure a genuine prospect of benefit and an acceptable level of risk </li></ul>
  11. 11. Protective concept of justice (continued) <ul><li>Requirement that benefits and burdens are distributed among social groups within the society. </li></ul>
  12. 12. A new concept of justice <ul><li>Participation in medical research is more of a benefit to be sought, than a burden or risk from which vulnerable patients required protection. </li></ul>
  13. 13. Possible pitfalls of the new concept <ul><li>Drug trials are valuable opportunities for patients and subjects to obtain health benefits for themselves </li></ul><ul><li>↓ </li></ul><ul><li>Blurred line between research and health care? </li></ul>
  14. 14. Proposed course of action <ul><li>Protective concept may have been exaggerated in some instances, but it does not mean it ought to be abandoned. </li></ul>
  15. 15. Essential elements to consider <ul><li>Need appropriate balance of: </li></ul><ul><li>Autonomy </li></ul><ul><li>Beneficience </li></ul><ul><li>Justice </li></ul>
  16. 16. Informed consent <ul><li>It is the first and most basic element of the protective concept of justice. </li></ul>
  17. 17. Informed consent (continued) <ul><li>Language of integrity, self determination, autonomy and privacy </li></ul>
  18. 18. Definition <ul><li>Free and informed consent encompasses a process which begins with the initial contact and carries through to the end of the involvement of research subjects in the project </li></ul>
  19. 19. Kant’s Imperative <ul><li>Moral objection to use another human being for a given purpose, legitimate or not. </li></ul>
  20. 20. Basis of research <ul><li>Research of objective knowledge requires that subjects/patients are considered in a unique way </li></ul>
  21. 21. Free and informed consent ? <ul><li>There is no question of using and taking advantage of individual, since it would be their own decision </li></ul>
  22. 22. Barriers to informed consent <ul><li>Acquiescence does not mean comprehension. </li></ul><ul><li>Possible barriers: </li></ul><ul><li>Patient-centered </li></ul><ul><li>Process-centered </li></ul>
  23. 23. Patient-centered barriers <ul><li>Illness </li></ul><ul><li>Hewlett , S. Consent to Clinical Research-Adequately Voluntary or Substantially Influenced?, Journal of Medical Ethics, Vol. 22, 1996, pp.232-237 </li></ul><ul><li>Schaffer et al. The Impact of Disease Severity on the Informed Consent Process in Clinical Research, The American Journal of Medicine, Vol. 100, 1996, pp.261-268 </li></ul><ul><li>Enrollment in research for treatment </li></ul><ul><li>Overestimation of benefits </li></ul>
  24. 24. Process-centered barriers <ul><li>Timing of consent </li></ul><ul><li>Readability of the consent form </li></ul><ul><li>Content of the consent form </li></ul><ul><li>Individual guiding the subject/patient through the informed consent </li></ul>
  25. 25. Overall message <ul><li>Informed consent goes beyond the printed document, and encompasses a continuum of patient/subject and investigator interactions and responses. </li></ul>
  26. 26. How to proceed? <ul><li>General consensus on the need for informed consent </li></ul><ul><li>↓ </li></ul><ul><li>Uncertainty on how to achieve meaningful consent </li></ul>
  27. 27. <ul><li>How to adapt the informed consent concept to vulnerable populations? </li></ul>
  28. 28. First case study <ul><li>Research on patients/subjects in Emergency Settings </li></ul>
  29. 29. Setting the case <ul><li>Patient temporarily incompetent due to </li></ul><ul><li>a traumatic injury, a myocardial infarction, a stroke. </li></ul><ul><li>Solution: Informed consent may be provided by a legal representative </li></ul>
  30. 30. Any foreseen difficulties? <ul><li>Legal representative may not be immediately available </li></ul><ul><li>Treatment cannot be safely delayed </li></ul><ul><li>Solution: Limit eligibility to patients who have a legal representative present to provide consent </li></ul><ul><li>Downfall: Accrual to study will be too slow… </li></ul>
  31. 31. Proposed alternatives <ul><li>‘ Deferred consent’ </li></ul><ul><li>Rejected by FDA/NIH in 1993 </li></ul><ul><li>Waiving of the informed consent </li></ul>
  32. 32. FDA ‘Final Rule’ Guidelines (1996) <ul><li>Treatment must be initiated due to life-threatening situations </li></ul><ul><li>Must impart minimal risk to the patient </li></ul><ul><li>Clinical investigation could not be carried out without the waiver </li></ul>
  33. 33. Final Rule Guidelines (continued) <ul><li>Waiving informed consent requires: </li></ul><ul><li>Community notification of the planned study </li></ul><ul><li>Exchange of negative reviews by IRBs/ECs </li></ul><ul><li>Establishment of independent data monitoring committees </li></ul>
  34. 34. Weak provisions? <ul><li>Community consultation/public notification </li></ul><ul><li>not enough feedback to the FDA? </li></ul><ul><li>negative community feedback may encourage site closure? </li></ul>
  35. 35. Questions remain <ul><li>What are the costs, benefits, feasibility of community consultations? </li></ul><ul><li>What aspects of community consultation are indeed effective for human subject protection? </li></ul><ul><li>Are there additional practices that could enhance human subjects’ protection? </li></ul>
  36. 36. Questions remain (continued) <ul><li>Are there elements of community consultation both procedural and substantive that should at a minimum be required? </li></ul><ul><li>Who should use the information obtained from community consultation process and how should they use it? </li></ul>
  37. 37. Current situation <ul><li>To date, few articles describing community consultation activities exist. </li></ul><ul><li>Predominant method used -> hosting of public meetings </li></ul><ul><li>Other proposed methods ->Random digit dialing telephone interviews, face to face interviews, focus groups. </li></ul>
  38. 38. Publications: Waiver of Informed Consent <ul><li>Mosesso and Cone, Using the Exception from Informed Consent Regulations in Research , Acad. Emerg. Med, Vol. 12, 2005, pp. 1031-1039 </li></ul><ul><li>Santora et al., Working through public disclosure process mandated by use of 21 CFR 50.24 (exception to informed consent): Guidelines for success , J. Trauma, Vol. 45, Issue 5, 1998, pp. 907-913 </li></ul><ul><li>Kremers et al., Initial experience using the FDA guidelines for emergency research without consent , Ann. Emerg. Med, Vol. 33, Issue 2, 1999, pp.224-229 </li></ul><ul><li>Baren et al., An approach to community consultation prior to initiating an emergency research study incorporating a waiver of informed consent , Acad. Emerg. Med., Vol. 6, 1999, pp.1210-1215. </li></ul>
  39. 39. Publications: Waiver of Informed Consent (continued) <ul><li>Mosesso et al., Conducting research using the emergency exception from informed consent: the public access defibrillation trial experience , Resuscitation, Vol. 61, 2004, pp. 29-36 </li></ul><ul><li>Morris et al., Exception from informed consent for pediatric resuscitation research: Community consultation for a trial of brain cooling after in-hospital cardiac arrest , Pediatrics, Vol. 114, 2004, pp. 776-781 </li></ul><ul><li>Dix et al., Implementation of community consultation for waiver of informed consent in emergency research: one institutional review board’s experience, J. Inv. Med., Vol. 52, Issue 2, 2004, pp. 113-115. </li></ul><ul><li>Contant et al., Community consultation in emergency research , Crit. Care Med., Vol. 34, Issue 8, 2006, pp. 2049-2052 </li></ul>
  40. 40. Other solutions <ul><li>Creation of a national independent advisory group </li></ul><ul><li>Obtain data regarding subjects and family members experiences, with exception from informed consent studies </li></ul>
  41. 41. Tri-Council Policy Statement <ul><li>Does not mandate public notification or community outreach </li></ul>
  42. 42. Canadian overview <ul><li>REBs must: </li></ul><ul><li>ensure additional patient protection </li></ul><ul><li>ensure thorough review of protocol/study design to confirm the ‘waived informed consent’ </li></ul><ul><li>↓ </li></ul><ul><li>Unusually lengthy approval process </li></ul>
  43. 43. Back to the beginning ? <ul><li>Can subjects who cannot voice their consent be protected if community speaks for them? </li></ul><ul><li>Are we not blurring the line between research and therapy, by implying that research studies requiring waiver of informed consent are therapeutic in themselves? </li></ul>
  44. 44. Second case study <ul><li>Research on patients/subjects facing cancer </li></ul>
  45. 45. Setting the case <ul><li>Patient with strong emotional feelings created by needs of self-preservation and multiple personal, psychosocial, economic and family concerns. </li></ul>
  46. 46. Competency to consent to research <ul><li>Requirement that a subject be competent to provide informed consent. </li></ul><ul><li>Evidencing a choice in regard to research participation </li></ul><ul><li>Factual understanding of the issues </li></ul><ul><li>Rational manipulation of information </li></ul><ul><li>Appreciation of the nature of the situation </li></ul>
  47. 47. Competency, subject to change? <ul><li>Over time </li></ul><ul><li>According to the choice to make </li></ul><ul><li>According to circumstances surrounding decisions </li></ul>
  48. 48. Any foreseen difficulties? <ul><li>Life-threatening illness affects the ability of the patient to rationalize what is best for him/her. </li></ul><ul><li>-> ‘ Emotional’ consent </li></ul>
  49. 49. Any foreseen difficulties? (continued) <ul><li>Overwhelming amount of technical information </li></ul><ul><li>Miscommunication about roles, expectations, study procedures. </li></ul>
  50. 50. Proposed alternatives <ul><li>What strategies enhance understanding? </li></ul><ul><li>What communication methods promote understanding? </li></ul>
  51. 51. Complexity/Nature of the Informed Consent Content <ul><li>Fractions or percentages for probabilities? </li></ul><ul><li>Verbal or written numerical probability value? </li></ul><ul><li>Numerical data is useful? </li></ul>
  52. 52. Complexity/Nature of the Informed Consent Content <ul><li>Are relative risks important elements? </li></ul><ul><li>Are decision making strategies similar within families or across cultural groups? </li></ul><ul><li>Graphic or text presentation of data? </li></ul>
  53. 53. Effectiveness of Various Delivery Systems <ul><li>Audio/Videotaped informed consent </li></ul><ul><li>communications </li></ul><ul><li>Ruckdeschel et al., Communication, Accrual to Clinical Trials, and the </li></ul><ul><li>physician-patient relationship: Implications for training programs, Journal </li></ul><ul><li>of Cancer Education, Vol. 11, 1996, pp. 73-79 </li></ul><ul><li>McHugh et al., The Efficacy of audiotapes in promoting psychological well </li></ul><ul><li>being in cancer patients: a randomized, controlled trial, British Journal of </li></ul><ul><li>Cancer,Vol. 71, 1995, pp. 388-392 </li></ul><ul><li>Written communications </li></ul><ul><li>Morrow et al., A simple technique for increasing patients’ knowledge of </li></ul><ul><li>informed consent to treatment, Cancer, Vol. 42, 1978, pp. 793-799 </li></ul>
  54. 54. Effectiveness of Various Delivery Systems (continued) <ul><li>Supplementary aids/tools (e.g. phone calls) </li></ul><ul><li>Aaranson et al., Telephone-based nursing interventions improve effectiveness of the informed consent process in cancer clinical trials, Journal of Clinical Oncology, Vol. 4, Issue 3, 1996, pp. 984-996 </li></ul>
  55. 55. Effectiveness of Various Delivery Systems (continued) <ul><li>Multimodality approaches </li></ul><ul><li>Interventions should not be crafted for a ‘one size fits </li></ul><ul><li>all” </li></ul><ul><li>Tailored to meet specific informational needs of </li></ul><ul><li>subjects </li></ul><ul><li>Involve more than one sense </li></ul><ul><li>Cognitive and emotional support </li></ul>
  56. 56. Question remains <ul><li>What is the most efficacious communication delivery system? </li></ul>
  57. 57. Back to the beginning? <ul><li>Society clearly cannot operates without rules </li></ul><ul><li>Individuals cannot always follow these rules </li></ul>
  58. 58. Conclusions <ul><li>Need to communicate clinical trial informed consent information in an understandable manner </li></ul>
  59. 59. Conclusions (continued) <ul><li>At the end… </li></ul><ul><li>is Subject/Patient’s only real protection </li></ul><ul><li>depending ultimately on the conscience and compassion of the investigator and his peers? </li></ul>
  60. 60. Contact information <ul><li>Veronique Brisson, B.Sc., MA </li></ul><ul><li>Associate, Clinical Quality Assurance </li></ul><ul><li>MethylGene </li></ul><ul><li>E-mail address: brissonv@methylgene.com </li></ul>

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