1. Conflict of Interest (COI) and the Consent Process Role of the Physician/ Investigator

2. COI and the Consent Process Fall 2003 Mary Weiss convinced her 26 year old son to come home to Minnesota where she could help him get treatment for his apparent psychiatric illness November 2003 Dr. Stephen Olson, MD recommended that the patient be committed to a state facility because of his delusions

3. COI and the Consent Process Mid November, Dr. Olson changed his opinion and declared Mr. Markingson had begun to acknowledge his need for treatment November 20,2003, a judge ordered Mr. Markingson to follow Dr. Olson’s treatment plan

4. COI and the Consent Process November 21, 2003, the subject signed an informed consent document to be a volunteer in the antipsychotic drug study called CAFÉ, Comparison of Atypicals for First Episode (randomization between Zyprexa, Risperdal or Seroquel). He also signed a hospital discharge summary that told him to follow Olson’s instructions, take his medication and attend all study appointments

5. COI and the Consent Process Winter, 2003, 2004 Markingson received Seroquel®, is a psychotropic agent belonging to a chemical class, the dibenzothiazepine derivatives

6. COI and the Consent Process December 8 th, 2003, the Mr. Markingson was transferred to a half way house Winter 2004, his mother wrote Dr. Olson and Dr. Charles Schulz head of the University of Minnesota’s psychiatry department, about her concerns regarding her son’s continued delusions and that they consider other treatment

7. COI and the Consent Process She considered but did not achieve legal guardianship. May 8, 2004, Mr. Markingson killed himself and upon autopsy, no drug was found in his system

8. COI and the Consent Process Many questions regarding the consent process are raised by this case: Capacity Comprehension Coercion

9. COI and the Consent Process The patient’s mother claimed in a law suit that the investigator had a conflict of interest since he had the dual role as her son’s primary physician who diagnosed his schizophrenia and the investigator who determined he met eligibility criteria for the clinical trial.

10. COI and the Consent Process The university’s web site offers guidance and advises “recruiting in a non-biased non-power-based manner” and goes on that “doctor patient relationships between the investigator and participants should be avoided, when possible, to eliminate any-power based coercion.”

11. COI and the Consent Process Pose this question: Should physician/ investigator who has this dual role be the one to manage the consent process with a prospective participant or is the perception of COI or the danger of a COI a real concern

12. COI and the Consent Process A conflict of interest is a set of conditions in which professional judgment concerning a primary interest tends to be unduly influenced by a second influence. Conflicts of interest are conditions not behaviors

13. COI and the Consent Process Financial conflicts of interest are well recognized, specifically in the realm of pharmaceutical sponsored clinical trials Potential for non financial conflicts of interests between the personal interests and agendas of the investigator and those of subjects is inherent in all research involving human subjects

14. COI and the Consent Process Examples of these non financial conflicts include: Benefits of publications, grants, Need for future funding pressures to complete a study and publish positive results The conflicts cannot be eliminated, but need to be recognized and managed if risks to subjects are to be minimized

15. COI and the Consent Process If an investigator is also the personal health provider of the potential research participant, there may be an additional conflict. Therapeutic misconception on the part of the potential participant Confusion on the part of physician/researcher regarding his/her role as care giver and investigator Fear on the part of the participant that he/she will disappoint or anger the physician if he/she does not agree to participate

16. COI and the Consent Process Yes, the physician already knows the patient, history etc. and there is the belief that physicians can judiciously balance the patients’ interests and those of the scientific protocol No, the physician can become conflicted by the two roles and the patient can also become confused and see the investigator only as a caregiver

17. COI and the Consent Process According to Alan Sugar MD, chair of the New England Institutional Review Board and professor of Medicine at BU, the problem is exacerbated when people are vulnerable, such as psychiatric patients. The IRB cannot resolve the problem, but must be aware of these issues, discuss options and offer viable solutions

18. COI and the Consent Process There are others who believe that all prospective participants who receive treatment as part of the clinical trial or who receive free services as part of the research are just as vulnerable

19. COI and the Consent Process Proposed Solutions: Have another investigator present the consent form and manage the process after the physician has identified that the patient may be eligible for the study. This person can also be available to answer questions. Education for physician/researcher to review regulations, the consent process and the dangers of COI or the perception of COI

20. COI and the Consent Process Continued education for the IRB members Assessment of policies and procedures at your institution Monitoring of the consent process for high risk studies

21. COI and the Consent Process None of these solutions is perfect. Non financial conflicts of interest are more subtle and cannot be eliminated Require vigilance on the part of the IRB, institutional leaders research mentors if they are to be managed successfully