Experts urge caution in early human drug trials
A group of experts has recommended more rigorous procedures for early stage testing of high risk therapies in the wake of the disastrous trial of TGN1412 at Northwick Park Hospital in March. The proposals include involving patients rather than healthy volunteers in early stage testing and giving the first dose to just one person at the outset.
The Expert Scientific Group was set up to investigate what happened when six healthy volunteers suffered severe reactions to the monoclonal antibody TGN1412. They were taking part in a phase one clinical trial (the first stage of testing on humans). Their limbs and heads swelled rapidly, their organs failed and medics struggled to keep them alive.
The group also looked at why TGN1412 gained approval for use in a human trial. In their report, the experts make a number of proposals to improve safety for future drug trials where similar therapies are tested in people for the first time.
The group considered written submissions from leading research organisations, scientists, consumer groups and the pharmaceutical industry. An interim report published in July 2006 recommends:
In drug trials of this type the first dose should be given to one person only, leaving sufficient time for any adverse reaction to develop before further doses or administration to more people.
In some circumstances and particularly if the drug is to affect the immune system, first studies may more appropriately involve patients being treated for the disease rather than healthy volunteers.
Earlier dialogue between the drug developer and regulator in the case of higher risk agents to allow thorough review of safety data.
Better international sharing of information about serious adverse reactions to drugs in trials.
The development of specialist centres to undertake phase one studies on higher risk agents.
The MRC Chief Executive Professor Colin Blakemore said: ‘Giving drugs to people for the first time will always involve an element of risk. The Expert Scientific Group’s report makes recommendations that aim to reduce the risk of volunteers suffering for volunteers like those who took part in the TGN1412 trial. It suggests ways to improve communication between trial regulators and drug developers to prevent human testing of potentially harmful pharmaceutical drugs. But we must stress that, although this was an extremely rare event, scientists and medics must continue to strive to reduce risks to humans. There are marvellous discoveries being made in basic research which promise to fight diseases better. Phase One trials are central to the process of turning those discoveries into clinical care but we must ensure that trials are rigorously scrutinised as potential new therapies emerge. The Expert Scientific Group clearly provides welcome advice. Scientists need to work more closely and share their findings when things go wrong as well as right.’
Members of the Expert Scientific group included MRC scientists Professor Janet Darbyshire, Director of the MRC Clinical Trials unit, and Director of the MRC Human Immunology Unit, Professor Andrew McMichael.
The recommendations will be open to consultation before a full report is published in late 2006.
