I was watching CNN International this morning and saw a story on a drug trial involcing something called "TGN1412" (a text version of the story is available at http://edition.cnn.com/2006/HEALTH/03/16/uk.clinical/index.html ). In a nutshell, eight persons participated, six receiving the drug TGN1412 and two receiving placebo. The six persons receiving the drug quickly developed severe "adverse reactions" (i.e., side effects) and two persons apparently are in critical condition. It is a very unusual for all participants receiving a drug to develop severe reactions and to do so quickly. A quick Google search of the web brought up a variety of websites mentioning TGN1412 and there is a growing number of articles in Google news (news.google.com) that are reporting this study. However, a search of Medline, first via Pubmed (pubmed.gov) and through my university's Ovid service produced no hits, a curious result given that the spokesperson for the company making the drug and sponsoring the drug trial has referred to previous research involving animals (oddly enough, the company appears unsure of which animals were used).
There are a couple of additional disturbing aspects to this situation beyond unusual adverse reactions: (1) Participants were well paid, 2,000 pounds or about $3,500. I don't really know whether this is an unusual amount to pay for participating in a drug study but in general terms it is a good sum of money that may attract people desperate for money. Indeed, at the British newspaper the Daily Mail reports, one of the participants did it for the money: |She said her boyfriend joined the trial on impulse |for financial reasons after his wallet had been stolen |and he had bills to pay. | |When she protested about him joining the programme |he replied: "I am helping mankind." http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=380028&in_page_id=1770 The issue of coercion readily comes to mind, that is, such studies are more likely to attract people who are poor or in financial difficulties rather than the general population -- the financial inducement to participate may trump other considerations such a potential dangers of participation. (2) Another involves who participates in such trials, beyond the issues of financial need: |The full test group was made up of four British Asians, |two Australians, a South African and one Englishman, |Mr Wilson. http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=380028&in_page_id=1770 The question of whether minority group members, defined on racial/ethnic grounds, may be coerced to participate (possibly through the mediating effect of income). There are other issues, some of which are highlighted in article below from the (London) Times, which also need consideration (e.g., initial number to treat). I have to admit that the one thing that bothers me the most is the absence of any mention in the scientific literature about TGN1412, implying that all of the research and associated findings is being "embargoed" by the drug manufacturer. One wonders how informative "informed consent" would be under such circumstances. -Mike Palij [EMAIL PROTECTED] New York University The Times March 16, 2006 Drug trial ignored guideline on safety BY NIGEL HAWKES, HEALTH EDITOR DRUG trials that left six healthy volunteers fighting for their lives did not conform to best medical practice, The Times has been told. Senior doctors expressed concern that all six were given the same dose of the experimental drug TGN1412 at the same time. According to the standard medical text, trials of this sort should avoid giving all the doses simultaneously. The Textbook of Pharmaceutical Medicine specifically gives warning that such practices can be "very difficult to manage" and "put subjects at unnecessary risk". Last night the Medical and Healthcare Products Regulatory Agency was urgently investigating what went wrong in the the trials, as families kept up a vigil at the patients bedsides. It is trying to determine whether it was a fault in production, contamination or more likely an intrinsic problem with the drug itself. "They haven't got a cure," said Myfanwy Marshall, whose boyfriend fell ill 90 minutes after taking the drug. "This is a drug they have never tested on humans before so they don't know what they are dealing with. It's completely messed up their vital organs." There was confusion last night about whether the drug had been tested successfully on animals before the tests on human volunteers. "They [the drugs company] said there was an oversensitivity in monkeys," Ms Marshall said. She went on to say that in the tests a "dog and some animals had died . . . so they reduced the amount to humans". Thomas Hanke, chief scientific officer of TeGenero, last night refused at a press conference to say whether animals had died during earlier tests. "There has been no issue on the safety of the drug on animals. This is not relevant," he said. He said the drug had been tested on mammals but not dogs or rats. He said that the company had apologised to relatives of the six ill volunteers. "We are devastated at these shocking developments which we were not anticipating. The investigation must proceed as quickly as possible (into) the testing of a new medicine which showed no signs of any safety problems in previous testing." Lawyers have been instructed on behalf of at least one of the victims. All six remained in care at Northwick Park Hospital, northwest London. Two were said to be in critical condition and the other four were serious, but showing signs of improvement. Relatives met doctors and staff from the two companies involved - the German biotech company, TeGenero, and Parexel, the contract company that was conducting the trial. The trial protocol had been agreed with the MHPRA and was carried out "according to strict ethical and regulatory requirements", according to Parexel. The MHPRA yesterday refused to give precise details, citing commercial confidentiality, and questions to Parexel went unanswered. But TeGenero confirmed that all six volunteers had been given scaled doses of the drug according to their body weight. The tragedy, experts said, should result in a review into the way future trial are carried out. Professor Sheila Bird, from the Medical Research Council's Biostatistics Unit at Cambridge, said: "It is very unusual to have a tragedy in one volunteer in a trial like this, far less to have all six involved. " That could have been avoided, she said, if at the start only one of the volunteers had been given the drug. All were healthy young men who had volunteered for the first human trials of a new arthritus drug, developed in Germany. Professor Bird, citing the recommendations made in The Textbook of Pharmaceutical Medicine, a standard work on the subject. suggested that the trial would have been better to test two or three volunteers on day one, before other volunteers were given their dose. However, Chris Springall of Covance Clinical Research, a company based in Yorkshire that carries out drug trials, said that the practice by which the whole group was given a dose at the same time was normal in the industry. But it was not considered risky because side-effects were so extremely rare. "I've been in this business 20 years and I've never known anything of this nature before," he said. Copyright 2006 Times Newspapers Ltd --- You are currently subscribed to tips as: [email protected] To unsubscribe send a blank email to [EMAIL PROTECTED]
