Guest Column | January 9, 2018

Clinical Trial Deaths — Will Clearer Informed Consent Documents Be Enough?

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In October 2017, the watchdog group Center for Responsible Science (CRS), along with clinical trial participants and the father of a deceased trial participant, grabbed headlines when it filed a lawsuit against the FDA. The suit takes aim at informed consent regulations, seeking to ensure that potential trial participants receive sufficient information to truly evaluate the risks and benefits of participating in a drug trial.

Will the lawsuit be successful? What steps do clinical trial stakeholders — drug companies, regulators, investigators, and others — need to take to improve the informed consent process and ultimately make trials safer for patients? For answers to these and related questions, Clinical Leader turned to David Rosen, co-chair of the life science practice at Foley & Lardner and a 14-year veteran of the FDA.

Since 2014, there have been more than 150 deaths related to clinical trial treatments. Should that be a concern for the industry?

David Rosen: Subjects who participate in clinical trials are a very scarce resource, so we need to make sure they are not subject to an unreasonable risk of harm and can safely participate in these clinical trials.

That’s why any death associated with clinical trials needs to be thoroughly investigated, so we can fully understand and appreciate why it occurred. It is especially important to do a substantive evaluation to see whether the death was related to the study, the drug or medical device, or the subject’s underlying medical condition. These evaluations should look at the subject’s entire medical and clinical record to determine the causation and what can be done to protect participants in future trials.

The Center for Responsible Science (CRS) filed a lawsuit against the FDA. Does any group have a chance of success in suing the FDA?

Rosen: Ultimately, it is difficult to compel the FDA to make clinical trials safer, and it is hard for a judge to hold the FDA responsible when it doesn’t have much control over all elements of a clinical trial. Based on my review and evaluation of informed consent documents, I know that the FDA takes the safety of those participating in clinical trials very seriously. In the early stages of the clinical trial initiation process, clinical investigators and study coordinators spend a lot of time thoroughly explaining the risks associated with the trials to potential participants.

These lawsuits seek to ensure that the documents given to subjects are clearer and more understandable. However, the FDA does not write these documents, the industry does. So the purpose and objectives, risk and benefits, and whom to seek out if there is a medical issues must be expressed clearly to those participating.

CRS believes that true informed consent means subjects must understand the drugs were tested in animal models, which are sometimes unreliable predictors of human response. Do you believe most study participants understand that?

Rosen: The informed consents that I have reviewed clearly outline the potential risks and benefits associated with these trials. Animal models are the best models we have to evaluate safety and the impact on body systems from a toxicology perspective. Of course, we have to be mindful of the safety of the animals being tested, but they are still the best models we have.

When considering whether participants in a clinical trial need to be aware of animal trials, I would say it really depends on the drug. It is difficult to determine whether telling someone that a drug caused a tumor in a rat will be helpful in making an informed decision as to whether or not to participate in a trial. The informed consent document needs to clearly explain the potential risks and benefits from participating in a trial. This does not diminish the need to outline the risks involved in clear and precise language, though.

We know consent forms can be long and complicated. Does the industry need a consent process that is more understandable to patients?

Rosen: I think the current informed consent process works fairly well. The onus is on the people administering consent to make sure they provide information to potential subjects so they understand the process and the potential risks and benefits. The potential participants should not feel rushed and should have the opportunity to ask any questions they have regarding the safety aspects of the product and the risks associated with participating in the trial. The industry needs to ensure the informed consent language is clear to identify potential risks and benefits to avoid confusion of the potential participants in the trial. Also, the principal investigators and study coordinators involved in procuring consent need to make sure the subjects involved fully appreciate and understand the potential safety risks and benefits of participating in the trial.

Is there one change you think we can make to the process that might make trials safer for patients?

Rosen: I think there are a couple things that can be done. First, we need to make sure that consent documents fully outline the risks and benefits associated with the study in a way that is easily understood by anyone enrolling in the study. And second, I think those who are administering consent need to take the time to make sure potential subjects fully understand and appreciate those risks and benefits of participating in the study, have the opportunity to ask any questions, and have ample time to make an informed decision.