Parexel

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PAREXEL International is a company based in Waltham, Massachusetts with offices all around the world, founded in 1983 by Josef H. von Rickenbach (still current CEO) and Anne Sayigh, that provides services for companies in the pharmaceutical, biotechnology and medical device industries, including consulting and clinical studies. The name PAREXEL comes from Paracelsus, a Swiss physician considered as the father of modern toxicology. PAREXEL employs more than 5000 people worldwide and is one of the most important pharmaceutical services companies.

1 TeGenero Clinical Trial
- 1.1 Conclusion of the MHRA
2 References
3 External links

[edit] TeGenero Clinical Trial

The neutrality of this article is disputed.
Please see the discussion on the talk page.

In March 2006, a PAREXEL-run trial on behalf of TeGenero, the now bankrupt German biotechnology firm, on its anti-inflammatory drug TGN1412, which was not designed with any specific illness in mind, but was proposed to possibly treat rheumatoid arthritis, multiple sclerosis or leukaemia, unexpectedly caused severe inflammation and multiple organ failure in six healthy volunteers at a facility based at Northwick Park Hospital in London^[1].

The drug had been previously successfully tested on animals. However, a documentary shown in the UK on 28th September, 2006 featuring journalist Brian Deer as part of Channel 4's Dispatches series exposed uncertainty about the existence of data that should mandatorily have been submitted by TeGenero to the Medicines and Healthcare products Regulatory Agency (MHRA) prior to the trial indicating whether TGN1412 had been adequately tested on human blood in vitro. Concerns were also raised about whether a safe human dosage was properly obtained by TeGenero.

A prominent immunohaematologist, who gave his own perspective on events surrounding the trial, stated in the documentary that the methods used by PAREXEL staff in administering the agent were 'reckless'. As this was a drug with a novel method of action and was previously untested for adverse reactions in vivo, the MHRA had originally recommended when approving the trial that the dose be administered over a 2 hour period. During the trial, however, the patients receiving the drug were given the full dose over a 3-6 minute period, and only 10 minutes apart from one another, thereby increasing the risk to multiple patients. Also, although severe adverse reactions were noted not long after the administration of the agent by the PAREXEL staff conducting the trial, 5 hours had elapsed before the patients were given proper assistance. Normal practice when a patient shows signs of severe immune response to an agent would be to administer hydrocortisone and an antihistamine immediately.

The programme concluded that PAREXEL acted with negligence, the trial was hurried, and that next of kin were not properly informed when things went wrong. Leigh Day & Co and Irwin Mitchell, the two law firms representing the six patients, are clear that they have a strong case against PAREXEL. In the documentary, Ryan Wilson, who nearly died in the trial has undergone multiple amputations, stated that the MHRA, PAREXEL, and TeGenero had thus far failed to apologise to him, or take responsibility for the blunders.

However, it should be noted that other opinion leaders believe that PAREXEL acted within all the current guidelines that exist for clinical trials (and this is also the conclusion of the MHRA investigations - see below), and that it is the guidelines that are at fault rather than PAREXEL or TeGenero per se. The unfortunate events at Northwick Park may lead to an examination of the whole range of drug testing regulations in the UK.

In November 2006 the company was criticized for paying a large bonus to the chief executive and founder Josef von Rickenbach, while the victims of the trial had still not received full compensation. Including his basic salary his bonus added up to $2,221,397^[2]^[3].

[edit] Conclusion of the MHRA

The MHRA published on 25 May 2006 a final report on these events which concluded that even if there were some discrepancies in the procedure, they did not cause the adverse effects which were observed:

This investigation indicates that the adverse incidents did not involve errors in the manufacture of TGN1412 or in its formulation, dilution or administration to trial participants. The MHRA therefore concludes that an unpredicted biological action of the drug in humans is the most likely cause of the adverse reactions in the trial participants. Monoclonal antibodies are a relatively new type of biological drug although there are a number of them already licensed and in use. However, TGN1412 is a new class of monoclonal antibody which has a stimulatory mode of action affecting certain types of cell in the immune system. In this case the resulting activity seen in humans was not predicted from apparently adequate pre-clinical testing. 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. (Conclusion of the final report)

The discrepancies concerned contracts and insurance procedures, failure to update the medical history file of a subject, permission given to the two placebo subjects to leave the hospital without checking that there were really the ones who were given the placebo, as this was a double-blinded trial (but the incident made this precaution unnecessary), and no system to provide a 24h medical cover. However, these discrepancies turned out retrospectively to be unrelated to the tragical events that occurred. ^[4]