CONFLICT OF INTEREST Judith Shayo BSc. MA. MBE.

COI Outline 1. What is unique to MUHAS guideline 2. A case study & reflections

CONFLICT OF COMMITMENT (UNIQUE TO MUHAS GUIDELINE) The University encourages its members to interact with the wider community, by undertaking sponsored research, consulting, and engaging in other activities, which may benefit the University, the public, or the individual. Such activities must be consistent with the principles of openness, trust, and free enquiry. When a University staff member accepts a full time appointment at MUHAS it is understood that he/she will accord the University his/her primary professional effort and will arrange outside professional obligations in such a way that it will not interfere with this commitment to the University.

Conflict of commitment … A conflict of commitment takes place when the commitment of a member of the University to external activities affects his/her ability to meet his/ her University commitments.

Conflict of commitment … The following guidelines should be abided to: In undertaking external activities, members of the University should take into account the possibility of conflict of commitment Time allocated to external activities should in total amount to 100% when combined with time allocated for all academic commitments. (45 hours a week as per Tanzania Labor Laws) In the event where there is a potential threat to academic commitments, the University member should disclose this in a letter to the head of department and indicate the mechanisms to minimize such threat.

CASE: COI & SAFETY OF RESEARCH SUBJECTS PATIENT X (18 years old) was suffering from ornithine trascarbamylase deficiency (OTCD), a rare metabolic disorder that prevents the body from breaking down ammonia. OTCD is caused by a single gene defect. Many children with OTCD die at a young age, but PATIENT X had a mild version and had a near normal life with medications and a special diets. His treating physician (who also was a PI in gene therapy study) considered PATIENT X a suitable candidate for gene therapy, an experimental treatment that attempted to replace defective genes with normal ones. The trial was testing a new mechanism (virus -vector) to deliver healthy OTC genes to patients' livers. Gene therapy was thought to have great ability to cure. PATENT X enrolled in an OTCD clinical trial. He knew he would not benefit from the study himself, but he wanted to help others. The trial PI told PATIENT X and his family that the clinical trial was relatively safe. However, shortly after the PI injected PATIENT X with the replacement genes his ammonia levels elevated to extremely high levels. After few days he suffered brain damage and multiple organ failure. PATIENT X died.

Case … An investigation was done about PATIENT X’s death, 3 issues were discovered: 1. Two monkeys died during the pre-clinical animal trial – Patient X and his family were not informed. This information appeared on the consent form submitted to the national research regulatory board, but did not appear on the form signed by PATIENT X. 2. Human volunteers in the same study had suffered adverse reactions - side effects serious enough to warrant termination of the trial if they were reported. 3. The PI was conducting the clinical trial for a private biotechnology company in which he had shares. The PI did not tell patient X and his family about the biotechnology company. If the PI could discover a safe way to deliver the normal OTC genes his company could patent the gene delivery system and use it to cure other, more common genetically linked disorders e.g. cancer. He would make millions of money out of his discoveries. He would get a job promotion

Case … Questions for reflections: 1.Do you think the PI could have acted differently if he had not had financial or/and academic interest in the gene therapy clinical trial? 2. Do you think PATIENT X would have changed his mind about participating in that clinical trial had any or all of these three issues been disclosed to him? 3. What would IRBs/research overseer do to make clinical trials safe? To protect human subjects?

Case Current situation: