Key data ‘missing’ in botched drugs trial

Essential information was missing before the TGN1412 drug trials took place that left the six men involved with serious lifetime illness, a study has warned today.

Research experts from the Netherlands applied their set of risk factors to the available data in the public domain regarding the antibody drug TGN1412 before the trials took place.

They found that the compound was unsuitable for administration to healthy people without additional pre-clinical experiments.

The men involved now face a lifetime risk of cancer and arthritis, and one man lost fingers and toes due to gangrene.

In the UK, scientific assessment is undertaken by the Medicine and Healthcare Products Regulatory Agency (MHRA).

Writing in the Lancet medical journal today, Dr Adam Cohen (Centre for Human Drug Research, Leiden, Netherlands) and Dr Marcel Kenter (Central Committee on Research Involving Human Subjects, The Hague, Netherlands) argue that the MHRA’s published document suggests that “the subreports are the result of isolated assessments from different individuals without much interdisciplinary interaction”.

“Moreover, the safety report contains several passages that seem to be copied from text that was supplied by the sponsor company in the investigator’s brochure. This work does not suggest independent critical assessment,” they write.

Drs Cohen and Kenter suggest their assessment scheme should be introduced to “ensure that all parties cover the indicated points in a transparent and critical manner, followed by a synthesis”.

Following the TGN1412 trial the government convened an expert scientific group to investigate what steps could be taken to improve the safety of drugs trials in the UK.

Its interim findings recommend 22 measures to increase the safety of volunteers in trials that are conducted for the first time in man. But the experts warn that the group’s work has not yet gone far enough.

“We welcome most of the recommendations of the expert scientific group but regret that important data are still not in the public domain for an independent and rational assessment by the scientific community,” they write.

In response to their findings the scientists are calling for all data from the TGN1412 trial to be made available for discussion by the international scientific community “so that lessons can be learned and better risk assessment can be developed that will protect future healthy volunteers in clinical studies to develop useful new medicines”.

Commenting on the report, a spokesman for the MHRA said that it has already implemented the scientific group’s interim recommendations and added: “Clinical trials in general have an excellent safety record but it is important that we learn the lessons from the TGN 1412 incident to optimise the safety of future phase one studies, particularly those involving novel and potentially higher risk medicines.”