Is it safe to participate in clinical studies?

By Pekka Simula 16 November 2017

Novelty implies risks. Sending humans in space, developing autonomous cars, designing faster sailing yachts – something unexpected can happen despite the most careful preparations, resulting in financial losses, injuries, or even fatalities.

Drug development implies novelty. For every new medicinal product there has to be a first-in-human clinical study, and the brave first person in the world who is administered the novel drug candidate. They have to accept certain risks; without them we would not have new drugs that may save thousands of lives or alleviate suffering in millions. Risks are managed through rigorous preclinical testing and strict regulations. As we reminded in one of our earlier blog posts a certain residual risk always remains. Fortunately drug development is relatively safe today; serious issues are rare though there are tens of thousands of interventional clinical trials ongoing all over the world.

And when something goes wrong every responsible developer working in the same field has to carefully re-evaluate their own situation. What is the relevance of the unexpected car crash on another similar development project? How can we prevent that from happening to us?

The pharmaceutical company Acorda Therapeutics recently announced the saddest possible news in drug development: In their large Phase 3 clinical trial with tozadenant, a novel drug candidate being developed for the treatment of Parkinson’s disease, the deaths of five patients are suspected to be associated with the clinical study. While the exact causality remains to be clarified in the ongoing investigations involving the US Food and Drug Administration (FDA), and its results will trigger further actions, everyone in the same field must again reconsider their own risks. Such assessment is critical for everyone developing a similar type of drug.

And everyone involved in a clinical study, or considering participation in a clinical study, is justified to reconsider. Does this impact their safety?

Tozadenant is a synthetic small molecule designed to impact the so-called A2a receptor. One of the roles of that receptor in the human body is the regulation of dopamine release in the brains, which makes it a potential target for the treatment of Parkinson’s disease. However the A2a receptor has also other roles. It is therefore possible that tozadenant could have contributed to the very serious side effects even though that had not been expected based on broad safety data including hundreds of patient-years on tozadenant or other A2a receptor antagonists. This will certainly cause additional safety precautions in the development of any A2a receptor antagonists. If I was in a clinical study with a similar drug I would definitely call my responsible investigator immediately and have a very serious discussion about my personal safety monitoring. I would even consider withdrawing from the study.

Personally I wouldn’t be concerned in the wake of the Acorda news if I was involved in a clinical study with any other kind of a drug candidate even in Parkinson’s disease. Especially if the study was being conducted in e.g. the Nordic countries known for highly professional and rigorous regulatory authorities. However I might still discuss the situation with my doctor, just for my own comfort, to verify my judgment. Even if I wasn’t directly concerned I would want to verify that any safety concerns of the patients are taken seriously.

We won’t have any new drugs without patients involved in clinical studies; so those patients definitely deserve to be heard.

Herantis develops two clinical stage drugs including CDNF for Parkinson’s disease. CDNF is an endogenous protein: A protein, which all humans have naturally in our brains and blood at all times though its amount declines as we age. This is expected to support a good safety and tolerability compared to traditional small molecule drugs, which are not naturally present in our body.

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