Two researchers from the McGill University question the current regulations for FIH (First-In-Human) clinical trials in a much commented article published in “Nature” on 30 January 2017. The authors Jonathan Kimmelman and Carole Federico point out that regulators in Europe and North America evaluate safety before allowing First-In-Human clinical trials to proceed, but they do not demand evidence for potential efficacy from pre-clinical animal tests.

Regulators assume that the companies will not test a molecule if there are no prospects for success, says Kimmelman. Academic ethics committees that approve clinical trials assume that the authorities have done the evaluation of effectiveness. They often take regulatory approval as a signal of clinical promise. So actually no one checks if the companies have done properly their homework.

Testing a molecule that doesn’t have a good chance of success is exposing people to unnecessary risks as it was seen in the tragic Phase I accident in Rennes, France an year ago. A volunteer died and four others had neurological sequelae in a first human test of a molecule interacting with the nervous system.

According to a report by the French authorities, the French CRO (Contract Research Organization) Biotrial would not have received from the Portuguese pharmaceutical company Bial, which invented the molecule, information on the adverse effects of monkeys from the pre-clinical trials. The Portuguese molecule also did not appear to be very effective, according to documents consulted by Mr Kimmelman

Such trials create unnecessary risks for participants and waste money at a time when drugs are already very expensive. If the authorities themselves assessed the potential efficacy of the new molecules, fewer clinical trials would be conducted and the drugs would cost less, advance the authors.

Today, the evaluation of pre-clinical evidence is especially important. The next US administration is likely to push the Food and Drug Administration (FDA) to lower the current requirements that a drug must demonstrate efficacy in humans before entering the market. If so, low standards for launching clinical trials in the United States could result in ineffective drugs being approved.

Commercial interests cannot be trusted to ensure that human trials are launched only when the case for clinical potential is robust. Expenses wasted on ineffective therapies and uninformative trials ultimately result in higher drug prices, the article says. We must abandon the fiction that current oversight systems are adequate to protect volunteers in first-in-human trials or to steward scientific efforts, conclude the authors.

The article suggests and justifies the creation of a centralized FIH advisory system that combines ethical and scientific review to mitigate the fact that Institutional Review Boards (IRBs) and clinical investigators often lack the resources and background to conduct such assessments. See the whole article here