MHRA Releases Selective Documents–Where is Informed Consent Document?

"It has found no evidence to suggest that there was any problem with the manufacturing of the product which was given to the trial volunteers – it appears not to have been contaminated, or to have contained anything other than the correct ingredients. Neither have we found anything in the way the trial was run which contributed to the adverse reactions experienced by the volunteers – it was run according to the agreed protocol, and the correct dose of the product was given to the patients."

“There are still further tests planned and until these are complete we cannot be firm about our conclusions.  However, if these findings were to be confirmed, it would indicate that this product showed a pharmacological effect in man which was not seen in pre-clinical tests in animals at much higher doses.  The Secretary of State for Health has therefore agreed to establish a group of leading international experts in the field to examine the issue further. The Group will need to review the evidence from the TGN1412 case and consider what necessary changes to clinical trials may be required”, says MHRA Chief Executive Professor Kent Woods.

However, we note that the the MHRA failed to release a copy of the Infomed Consent document.
That failure to reveal to the public what was disclosed to the volunteers who were victimized in the experiment is, in and of itself, a demonstration of the low regard  the MHRA has for the legal obligations toward human subjects of research.  Foremost is the duty  to fully disclose to the subjects all the known and potential risks in the written informed consent document.

What possible justification is there for withholding from public view, the one document that the unfortunate volunteers were shown ?

The selective summaries of documents pertaining to the catastrophic experiment TGN1412 are posted at.
See:
http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary=true&ssDocName=CON2023515&ssTargetNodeId=389

The Times (UK) reported that Kent Woods, chief executive of the MHRA, said yesterday that" future trial applications for biological agents would be subject to new levels of scrutiny."

Professor Woods said that the interim report raised questions about the potential risk involved in human trials, particularly the new “superagonistic” class of monoclonal antibodies, such as TGN1412, which work by stimulating action affecting cells in the immune system. Many monoclonal antibodies work by blocking immune actions, rather than encouraging them. “In this case the resulting activity seen in humans was not predicted from apparently adequate pre-clinical testing,” Professor Woods said.

In the U.S. the FDA adopted dangerous and ill-advised new rules that will INCREASE inadequate pre-clinical testing, thereby increase risks of harm for human subjects.

 See: http://www.ahrp.org/cms/content/view/121/26 and Nature  Drive for drugs leads to  baby clinical trials: US regulators are moving sharply to ease the early stages of drug development, despite safety concerns.  Meredith Wadman reports March 22, 2006 http://www.nature.com/news/2006/060320/full/440406a.html

 

Contact: Vera Hassner Sharav
veracare@ahrp.org
 


http://www.timesonline.co.uk/article/0,,2-2120897,00.html
The Times
Scientists are cleared of blame for drug trial that went wrong
By Sam Lister, Health Correspondent  The TimesApril 06, 2006

TOUGH rules are to be introduced for drug tests on people after an interim report on the disastrous trial at Northwick Park Hospital found no evidence of human error, contamination or failure to follow protocols.

The findings yesterday suggested that the drug TGN1412 caused an unprecedented and unexpected reaction that did not occur in tests on animals.

Uncertainty over the entire class of drugs similar to TGN1412— monoclonal antibodies — will remain until the chemical trigger that caused the adverse reactions is identified.

Most of these drugs alter the behaviour of the human immune system and are used to treat many diseases, including cancer and arthritis.

Kent Woods, chief executive of the Medicines and Healthcare products Regulatory Agency (MHRA), said yesterday that future trial applications for biological agents would be subject to new levels of scrutiny.

They will now be seen by the Commission on Human Medicines as well as the MHRA, with further external experts brought in ad hoc should any doubts remain.

About 10 per cent of the 360 phase 1 trials each year are likely to be affected. The MHRA said that the 40 monoclonal antibody trials accepted since May 2004 had been reviewed to assuage any other concerns.

Professor Woods said that the interim report raised questions about the potential risk involved in human trials, particularly the new “superagonistic” class of monoclonal antibodies, such as TGN1412, which work by stimulating action affecting cells in the immune system. Many monoclonal antibodies work by blocking immune actions, rather than encouraging them. “In this case the resulting activity seen in humans was not predicted from apparently adequate pre-clinical testing,” Professor Woods said. “This is a complex scientific issue which raises important scientific and medical questions about the potential risks associated with this type of drug and how to make the transition from pre-clinical testing to trials in humans.”

A working group is also being set up by the Government to examine the transition from animal tests to studies in humans involving biological agents with novel actions. It will look at how trials can be conducted using new drugs that have a “highly speciesspecific action”, drugs that are directed towards the immune system and the broader science surrounding monoclonal antibody treatment.

Gordon Duff, Professor of Molecular Medicine at Sheffield University, will head the group, which will also include international experts. Professor Duff is the chairman of the Commission on Human Medicines and the National Biological Standards Board and a former chairman of the Committee on Safety of Medicines.

His group is expected to give its initial findings to Patricia Hewitt, the Health Secretary, within three months, but no date is scheduled for its final conclusions. These would form the basis of a further refinement of drug trial protocols, Professor Woods said.

The MHRA said that it could not be firm about its findings and further tests were planned, but it appeared that the Northwick Park drug did not contain “anything other than the correct ingredients”.

Six men were taken into intensive care with multiple organ failure hours after being injected with the drug, which was designed to treat chronic inflammatory conditions and leukaemia. The trial was run by Parexel, a pharmaceutical research company, on behalf of TeGenero, a German company that designed the drug.The MHRA chief executive rejected suggestions that his agency should not have allowed the trial to go ahead with a protocol that involved the testing of six healthy volunteers in quick succession.

A paper from the Academy of Medical Sciences, published yesterday, questioned the practice and said that it would be usual “to administer a single dose in a single patient, who would then be observed for an appropriate period of time”.

OUT OF DANGER
Six of eight men recruited for the TGN1412 trial fell seriously ill within hours of being injected with the drug on March 13

The men were taken into intensive care at Northwick Park Hospital. They were described as suffering multiple organ failure

Navneet Modi, 24, Mohamed Abdelhady, 28, a New Zealander and another man were discharged after several weeks in the unit

A fifth man went home yesterday. It is believed that Ryan Wilson, a student from North London, is the last still in hospital. He is no longer in intensive care

Copyright 2006 Times Newspapers Ltd.