GxP Perspectives receives some excellent questions and comments about best practices. Here a regular reader asks a very pertinent question on Oncology Research. I don’t have the answer but I am hoping that the GxP Perspectives Community has some people that can help answer this for George. I hope so because I can learn a few things as well. Please comment if you have ideas for George and others to pursue.
An Ethical Question on Medical Oncology Research:
I am not sure the best place to post this question: I work in Medical Oncology Research and I have been noticing what I feel to be a distubing trend in manditory tumor tissue submission. In the past, studies required tissue samples if they were needed to determine eligibility or randomization to a treatment arm (Essentially something that was a potential benefit to the patient or needed to deterimne if study endpoints were met). Those studies usually gave patients the option to allow the sponsor to keep archived tissue for “future testing” that had no benefit to the patient or current study. Recently, some sponsors have been requiring this “archived tissue” as part of the inclusion / exclusion criteria – “If you don’t give us the tissue, you can’t go on our study.” Do you know if anyone is discussing this issue or is concerned how this may impact patient rights?
Three Comments. The first is from Abby: If the intended use of the archival tissue sample is to send to a central reader to show that the subject indeed has the pathological diagnosis intended for the study, I believe this is a legitimate and important request by the researchers. In the case of a more nebulous use (e.g. “general exploratory pharmacodynamic studies” or “future use”), I do think it is good if the Sponsor can try to provide more specifics, such as “future use in cancer research” or something even better.
It has been my experience that the Informed Consent wording related to these samples must be very clear, and address the short-term and long-term storage of the samples, as well as information on how the subject may revoke that consent and have the samples returned. Clinical sites often request return of the archival samples on behalf of the subject, and sponsors often return the samples–especially if the subject is moving onto another study that also likely requires tissue. Interesting question–and I look forward to hearing other responses!
And the second is from Kevin: As far as the patient’s rights, they aren’t affected at all. As you state, it is clearly in the Inclusion criteria that if you want to participate, the Sponsor requires this sample. This should be included in the consent form as well. The patient, at this point, has the right say “no” to the study.
Sponsors routinely collect these samples as a way to further their research and hopefully capitalize on a novel therapy. I guess you can look at this in one of two ways: 1) Big Pharma is trying to make a dollar (…obviously, which is how/why they exist in the first place) or 2) since they have the ability to take the research beyond the confines of the current protocol, they may just find a cure or improved therapy, which in turn, benefits the patient.
It would be unethical only if the Sponsor took the sample and archived it without the patient’s consent.
My suggestion would to be to discuss your feelings with the Sponsor or to start with, perhaps your IRB.
And Eleanor: There is currently a significant shift in the approach to cancer treatment. In many cancers, there is not a universal response to treatment but some sub-populations respond much more effectively to treatment than the general population. In many cases this response to treatment relates to expression of certain genes by the tumour that do not occur in all patients with the disease. If it is possible to identify the gene and which patients express that gene then treatment is much more effective both in terms of success and in terms of cost.
This may be one of the reasons that sponsors are moving towards mandatory collection of samples. If they identify that a particular sub-population has responded more effectively they can go back and examine stored samples to try and identify the reasons that the sub-population responded more effectively. Thus, there may be the possibility of developing diagnostic tools to identify the sub-population and only treat that population. If there are only limited samples available then it may not be possible to do so. Just a thought…..
Please leave a comment on this question. Thanks!
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Guidance for Industry: Oversight of Clinical Investigations — A Risk-Based Approach to Monitoring
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