A clinical trial that landed subjects in intensive care has raised concerns about the process
A drugs trial in the UK that went disastrously wrong last month has raised questions about the ethics of using paid volunteers in clinical trials and the usefulness of animal testing.
As Chemistry World went to press, two men remain critically ill after taking part in a Phase I trial of the fully humanised monoclonal antibody TGN1412, which was developed to treat chronic lymphocytic leukaemia, multiple sclerosis and rheumatoid arthritis.
The drug stimulates the activity of the human immune system protein CD28 which is present on the surface of a subgroup of white blood cells called T lymphocytes. The developers predicted that patients with leukaemia might be able to eliminate the cancer cells themselves.
The six men who received the drug all experienced an inflammatory reaction leading to organ failure.
The Medicines and Healthcare Products Regulatory Agency (MHRA), which authorised the trial, is investigating what went wrong. It is considering whether the reaction the men suffered was caused by a dosing error during the trial conducted by Parexel, or contamination during manufacture, or whether it was an unanticipated side effect of the drug in humans.
This latter possibility has raised questions about the validity of preclinical tests on animals of such a humanised drug. TGN1412 was tested extensively in laboratories and has been tested on rabbits and monkeys. TeGenero, which developed the drug, saw no drug-related adverse events.
But could these animal tests have given falsely reassuring results? It will be some time before the MHRA issues its conclusions on the cause of the men’s reaction, but some have questioned whether testing this drug on healthy volunteers was the right option.
Phase I trials are often conducted on patients for whom the risk/benefit equation is worthwhile. But no toxic effects were expected with this drug, so the decision was made to use healthy volunteers.
If it is discovered that an unanticipated side effect is to blame, other ways of conducting trials for these types of drugs might be needed. One option is micro-testing, which involves testing a microscopic amount of a drug on a blister on a person’s arm.
Another concern following the incident is that it may put people off volunteering to take part in clinical trials. These trials are fundamental for medical research; without them we would not have any new treatments or vaccines.
But, initially at least, this fear seems to be unfounded. Medical groups that conduct clinical trials have had more enquiries about volunteering since the incident. It would be worrying, however, if this was due to people realising they can make money from the process.
Clinical trials are essential to develop new drugs and people should take part with that in mind, not lured into it by the prospect of fast cash. Under current guidelines, payments can only be made for time lost and inconvenience caused. Trials are not meant to be a way to make a living. But the constant need for volunteers means that advertising is vigorous. Perhaps it is time to reconsider the clinical trials process.
Karen Harries-Rees, editor