Point for Discussion
We have submitted an Investigator-initiated research study ( including a clinical trial ) to the University of Alexandria for fund. The project was among hundreds of projects submitted from different Faculties and Institutes of the University. Fortunately, the project was approved for funding , however, ethical clearance from the our REC was not yet obtained.
The project includes testing a drug- that is commercially used for different indications- as a treatment for a disorder that has no standard of care and that constitutes a major national health problem in our country.
The REC queries came from the fact that the drug has a long list of adverse effects especially in females in the child-bearing period ( being a hormonal agonist ), however, the FDA approved its use in some indications based on assessing the risk: benefit ratio and on the fact that the majority of those AEs are dose & duration-related i.e., usually don’t occur when the drug is used for < 6 months and even there are reports that the drug was well-tolerated even when it was used for longer durations. In the current study we ‘re going to use it for 3 months only within the recommended dosage range and close monitoring of the subjects for any clinical or laboratory evidence of AEs will be adopted ( on frequent weekly visits ). Also, strict inclusion & exclusion criteria were put in the protocol in order to minimize the chance for occurrence of such AEs and all those AEs are clearly mentioned in the Drug-information Leaflet and in both the Arabic and English versions of the ICF.
The REC sent to us its queries regarding subject safety and we replied explaining the above-mentioned points in full details, however, they sent to us another report that the drug is not safe and they are not convinced to approve its trial in our indication.
My Questions are :
1. If the drug is already being used for such or similar indications ( Off-label use ) and we have some promising efficacy and safety data about it, Are we justified to submit those data to the REC to support us ? Do we need to obtain patients’ consent for submitting their data to the REC ?( those patients are treated in our clinics or at the Health Insurance Organization and they know well that the drug is not yet approved for treatment of their disease and that we are trying it because their condition has no standard of care and fortunately the majority of them improved with mild or no adverse events ).
2. While discussing the issue with one of our Junior staff, she suggested to exclude pre-menopausal females from enrollment in order to satisfy the REC and to include only males or post-menopausal females. I think this will affect the scientific integrity of the research and will deprive a significant proportion of female subjects of their rights to participate in this research and to benefit from such promising drug.
3. One of our colleagues suggested that we can ask the REC to give us approval for enrolling , for example five subjects only- to start with - and to follow those subjects with us for safety issues ( similar to phase I trials ) . If everything is fine, then they can approve enrolling more subjects ---and so on . Is this applicable or feasible ??
Thanking you in advance and Waiting for your valuable comments .
- Dear Dr Nadia
The drug you refer to appears to have toxicity in a selective group of patients, using it for a long duration. Exclusion of this group will not hamper the results of the study but will make them extrapolatable to similar patient in the general population. A second study would then be needed for this high risk group with certain restrictions as you mentioned (limited duration of treatment, pilot study, closer monitoring, etc).
You could also get signed patient testimonials about their use of the drug and their experience to be put in front of the REC.
This is my opinion and I would like to view the opinion of our colleagues on this point of discussion.
Professor of Clinical Oncology
Alexandria Faculty of Medicine
Editor, Bulletin of Alexndria Faculty of Medicine