Higher Standards Needed for Drugs Advancing from Preclinical to Clinical Trials

Standards that are used to justify moving a drug from preclinical to clinical trials need to be strengthened, according to a study published by Nature.

The authors believe that the current standards allow for clinical trials in humans without adequate evidence of clinical benefit. Regulatory agencies in North American and Europe require safety data be presented prior to authorizing clinical trials, but they do not require efficacy data. This is where the investigators believe standards currently fall short.

“We believe that many (first-in-human) studies are launched on the basis of flimsy, under-scrutinized evidence,” the authors wrote.

Even if study participants do not sustain harm from the drug, a significant financial burden is placed on society due to research and development costs, according to the study. Drug development requires substantial research and financial resources, which may be passed on to consumers by increasing the costs of approved drugs, especially in the case of drugs that fail in clinical trials.

Additionally, patients enrolled in clinical trials of ineffective drugs miss an opportunity to enroll in a trial for a beneficial investigational treatment. This could increase costs for the patient due to diminished health, and related events experienced in the future.

Since President Donald Trump has expressed the desire to reduce requirements for clinical evidence of efficacy prior to approval, increasing scrutiny of animal studies may be appropriate, according to the study.

In France, a clinical trial lead to the death of 1 patient, and hospitalized 5 others. Although the drug’s unknown toxicity was greatly scrutinized, ethical review boards rarely evaluate whether an investigational drug should be explored for human use.

These review boards are formed at research and educational institutions to protect patients in clinical trials, according to the study. Increased utilization of these committees is a simple way to implement a beneficial change to clinical trials.

"Commercial interests and hope, alone, cannot be trusted to ensure that human trials launch only when the case for clinical potential is robust," said researcher Jonathan Kimmelman, PhD. "Ethics requires a clear-eyed evaluation of a drug's potential."

The authors suggest multiple ways to reinforce more stringent efficacy standards to ensure that investigational drugs are beneficial.

Negative results from animal studies should be submitted to researchers and ethics committees who should conduct analyses on the information to determine if further testing is warranted. Clinical trials should only be authorized if the preclinical findings are confirmed after a review by independent experts, according to the study.

Reviewers should take into account numerous pieces of evidence to better determine if an investigational drug could be clinically beneficial. Understanding how drugs in the same class have performed in clinical trials could provide reviewers with additional insight, according to the study.

Critics may say that this proposal could lead to increased costs and time for drug development, which may limit therapeutic options for patients. However, thorough analysis before initiating clinical trials could reduce failures, which may neutralize development costs, the study concluded.