Richard Smith: What should a patient ask before entering a clinical trial?

richard_smith_2014“What,” a Finnish journalist asks me, “should a patient ask before entering a clinical trial?” That’s a good question, I think, as on my feet I try to answer the question. So here’s an attempt at an answer.

She asked me the question because I’d been saying that much that is published in medical journals is wrong, many trials are never published, and many trials are more for the benefit of drug companies than patients.

The first thing patients should ask, I suggest, is whether the trial will be published together with the full dataset so that everybody can access the results and reanalyse and reuse the data. If the answer is no to any part of the question then I suggest that the patient declines to participate. A secondary question will be to ask how confidentiality will be guaranteed as far as possible, recognising that there can be no 100% guarantee.

The beauty of these questions is that it shouldn’t be difficult for a patient to understand the answers. They will detect any wheedling by the researchers and can withdraw.

A more important question but perhaps one where it will be harder to be confident about the answer is whether the trial addresses a question that is clinically or scientifically important and will benefit other patients. The researchers will, of course, insist that the trial is of great importance, and it may be too easy to baffle the patient. The patient should, however, be able to make a fair stab at understanding whether the research will benefit patients. It might also be that patients are willing to participate in a trial that will be valuable scientifically but of far off—or even no clear—benefit to patients, but it will be harder for the patient to judge the scientific value.

A related and easier question to interpret is who is funding the trial. If it’s being funded with government money—perhaps the Medical Research Council or the National Institutes of Health—then there is a higher chance, but no guarantee, that the research question is scientifically or clinically important. Funding by a pharmaceutical company does not mean that the question is not important, but it should make the patient more sceptical. In contrast, funding by a charity does not automatically mean benefit for patients as charities are often more easily misled by researchers than most government-funded bodies.

The patient should also ask whether the researcher will be paid for entering patients into the trial or has some other financial conflict of interest—like a patent or equity in a company. Non-financial conflicts, not least career advancement, may be just as powerful, but financial conflicts of interest should raise the patient’s level of scepticism.

Now we come to perhaps the hardest question: will the trial provide a confident answer to the question being asked? I wrote a blog recently about teaching children to make decisions about health choices, and the 32 concepts that they should ideally be taught are exactly those that are applicable to the patient thinking of entering a trial. These concepts, which have been gathered together, cover topics like are the groups in which the treatments are being compared comparable, are the groups big to overcome the play of chance, are side effects being considered, and do the outcomes matter to patients. An assiduous patient might print out the concepts and run through them with the researcher.

Patients might judge the likely value of the research not only by the answers the researchers give, but also by how they answer the questions. If they become impatient and irascible then the patient should be beware, and I suggest that patients shouldn’t trust a researcher who says something like “Don’t you trust me?”

Clearly if patients conclude that the methods will not answer the question confidently then they should decline to participate. (Perhaps too they should notify other patients of their concerns.)

There are then the routine questions that patients are expected to ask: What exactly will happen to me? What are the risks? How long will the trial last? But these questions are irrelevant if the research question isn’t worth asking, the methods won’t answer the question reliably, or the results and data won’t be shared with all.

Researchers are not used to being asked such questions, and some might be astonished—and even offended—to be asked, but patients have an important, even if so far largely unrealised, role to play in raising the relevance and quality of clinical trials and, indeed, all research. Researchers should be delighted to be asked such questions.

Competing interest: I’ve participated in only one clinical trial, and I didn’t ask these questions even though I should be better equipped than the average patient to interpret the answers, but I will ask them next time.