Longevity Briefs: More And More Clinical Trial Protocols Are Getting Amended - And It's Expensive

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Every clinical trial investigating the effectiveness of a new drug or intervention starts with the development of a clinical protocol. This is a document that lays out exactly how the trial will be conducted – what the objectives are, how participants will be recruited, how the data will be collected and so on. This ensures the safety of the participants and the integrity of the data collected. If any major changes to the protocol need to be made after the trial has begun, this is a significant setback that can delay the completion of the trial and increase costs considerably.

What did the researchers do: The Tufts Centre for the Study of Drug Development, a non-profit research centre within Tufts University School of Medicine in Boston, analysed data concerning amendments made to clinical trials throughout the previous decade.

Key takeaway(s) from this research: The Tufts Centre found that from 2018 to March 2020 (before research was disrupted by the pandemic), the number of protocol amendments for Phase 1, 2 and 3 trials averaged 2.4, 2.7 and 3.3, respectively. For comparison, these numbers were 1.8, 2.2, and 2.3 from 2013 through 2015. Well over 50% of all trials received at least one substantial protocol amendment – 78% in the case of phase 2 trials specifically. They also found that protocol changes were particularly common in certain types of clinical trials, such as those for cancer drugs, drugs for rare diseases, and trials outsourced to contract research organizations.

These amendments are both time consuming and costly: Tufts researchers found that if a phase 3 trial made just a single protocol amendment, this required an average of $535 000 in additional costs and prolonged the completion time of the study by three months.

So, why the rise in amendments over the years? According to Tufts Centre head Kenneth Getz, clinical trial protocols are becoming more complex and eligibility criteria more restrictive, which means the trials sometimes fail to recruit enough participants – a problem that may be exacerbated in certain patient populations such as those with rare diseases. This means that either the eligibility criteria must be relaxed, or the trial must proceed without having reached its recruitment target, both of which are substantial amendments.

As for contract research organizations, the increased rate of reported amendments may simply be because trial sponsors tend to outsource the hardest and most complex trials.