Maurice Macdonnell

In the circumstances it is mny statutory duty to report to you, The MATTER OF CONCERN is as follows. The decision to administer the second dose after fatigue and ptosis had developed was taken by the doctor who was also the investigator in the research study: There would appear to be a conflict of interest between the benefits of keeping the patient in the trial in the interests of research and the potential risks to health of the patient from receiving the second dose; if that decision is taken by the same doctor. Director BMS R&D advised that the research had received UK Ethics Committee Approval, but this approval was not received as evidence by the court: He advised in his experience in international trials, there was no such arrangement of different doctors to deal with this conflict of interest: He pointed out that the severity of reaction was not enough to require stopping the according to the protocol, but he would want the stopped if it was likely the changes were related to administration: He encouraged clinical exploration of alternative diagnoses. The letter of response to the enquiry made of BMS by the research nurse advised "hold any further study administration After the inquest the R&D director wrote to the coroner explained the extensive training of investigators and they have access to a medical monitor; who attends a committee to see if any modifications are required in the trial for reasons He also informs the court that introducing an independent adjudicator could pose risk of bias and burden of bureaucracy: ACTION SHOULD BE TAKEN The court not had the benefit of independent opinion as to whether the arrangements in this or indeed other trials, adequately protects patients when the conflict of interest identified above arises_ It would seem prima facie to create & potential risk to but the MHRA would seem to be the appropriate body to make a judgment on this matter _ It is understood that the adverse reaction has already been reported to the MHRA and that new guidance has been issued: If action is required the MHRA may choose to communicate that to the hospital, pharmaceutical company and/or investigator; who are into this report; as may be in positions to take further actions to prevent future deaths risk drug drug, drug drug drug safety has lives, drug any copied they

YOUR RESPONSE You are under a to respond to this report within 56 of the date of this report; namely by 9h August 2017. 1, the coroner, may extend the period. Your response must contain details of action taken or proposed to be taken, setting out the timetable for action: Otherwise YoU must explain why no action is proposed If you require any further information or assistance about the case_please contact the case officer COPIES and PUBLICATION Ihave sent a copy of my report to the following Interested Persons: At King's College Hospital: The Research Ethics Committee Consultant oncologist) (study investigator) Bristol Squibb (R&D Director) Iam also under a to send the Chief Coroner a copy of your response: The Chief Coroner may publish either or both in a Or redacted or summary form: He may send a copy of this report to any person who he believes may find it useful or of interest: You may make representations to me, the coroner, at the time of your response, about the release or the publication of your response by the Chief Coroner _ [DATE] [SIGNED BY CORONER] [4 - 6-17 duty days Myers duty complete