Globally there are many guidelines for good clinical practice to ensure research is ethical and rigorous in conducting clinical trials to prevent harm to the participants and in the vast majority of drug developments the safeguards are effective.  This is a tragic event and requires detailed investigation to ensure all quality controls were in place. In my experience drug companies are meticulous in monitoring clinical trials and it will be of interest to the global research community to identify what happened in this instance. Our availability of analgesics for management of pain has improved over the last few decades but there are significant adverse effects from all strong analgesic so further drug development and research is essential and this event will impact on drug development in this area of clinical practice for a long time.

The disastrous results of a clinical trial for a new pain killer has sent shockwaves around the world. As yet, we do not have enough information to understand why this drug caused brain damage and death, or why these effects were not seen in preclinical testing of the drug. Before a drug is tested in humans, it undergoes testing in tissue culture and animals to determine both if the drug works and if it has toxic effects. No drug goes into a clinical trial until we have a clear idea of its toxicity in animals (and potential toxicities using tissue culture).

Serious adverse effects to experimental drugs are exceedingly rare, and this may be the worst ever under modern safety procedures. We don’t know the extent of animal testing for this drug at the moment, but we know that the drug was tested in chimpanzees, in case there were primate specific toxicities that would not be picked up in other animals.  

When drugs are first tested in humans, the first thing that is looked for is human toxicity. Doses are typically low and increased carefully with monitoring. In this particular case, the drug prevents the breakdown of endocannabinoids, substances that our own body produces but have actions similar to cannabis. Other drugs that act in the same way have been through preclinical and clinical trials with no evidence of the devastating side effects seen in this clinical trial. At the moment we can only speculate about why this has occurred, and why our clinical trial safety measures failed, but this will be actively investigated and clinical trial procedure reviewed in the light of these investigations.