On 17 March Mike Palij wrote in relation to the drug trial that went wrong:
>Well, I doubt that the companies involved will be >releasing any background about the participants, much >in the way that the drug manufacturer has "embargoed" >info about earler studies involving TGN1412. What >has been released in the press and media about the >background of the subjects should raise some concerns. Why would this depend on the companies involved? In the coming days and weeks theres nothing to stop relatives, or the victims themselves if and when they recover, from talking to the press. No doubt at present the relatives don't want press intrusion, but there has been a smattering of information about the participants. For instance the Daily Mail reports the words of one of the participants who was given a placebo, Nick Whybrow, described as a bar manager. And one of the victims is reported by his girlfriend to be Ryan Wilson, a student. Incidentally, re the original report on the participants in the Daily Mail (not recorded in any other paper I have seen over the last few days), one of the two Australians among the participants has now metamorphosed into a New Zealander. Well, more or less the right part of the world. -:) Allen Esterson ------------------------------------------- Fri, 17 Mar 2006 12:29:14 -0500 Author: "Mike Palij" <[EMAIL PROTECTED]> Subject: Re: Ethical Issues When Drug Trials Go Spectacularly Wrong > On Fri, 17 Mar 2006 06:34:04 -0800, Allen Esterson wrote: > > >Mke Palij writes in relation to the tragic outcome of the drug trial > >[snip]: > >>(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: [... > > > >I would have thought that most people participating in > >drug trials would be doing it primarily for the money. > > Well, it depends upon a variety of factors. In the U.S. > the Department of Health and Human Services provides > regulations and oversight on drug trials, structuring the > testing of new drugs through four phases: > > (the info below is taken fromt he following website which > provides additional coverage: > http://www.hhs.gov/ohrp/irb/irb_glossary.htm ) > |PHASE 1 DRUG TRIAL Phase 1 trials include the initial > |introduction of an investigational new drug into humans. > | > |PHASE 2 DRUG TRIAL Phase 2 trials include controlled > |clinical studies conducted to evaluate the drug's effectiveness > |for a particular indication in patients with the disease or > |condition under study, and to determine the common short-term > |side effects and risks associated with the drug > | > |PHASE 3 DRUG TRIAL Phase 3 trials involve the administration > |of a new drug to a larger number of patients in different clinical > |settings to determine its safety, efficacy, and appropriate dosage > | > |PHASE 4 DRUG TRIAL Concurrent with marketing approval, > |FDA may seek agreement from the sponsor to conduct certain > |postmarketing (Phase 4) studies to delineate additional information > |about the drug's risks, benefits, and optimal use > > From the info provided in the news articles, the drug TGN1412 > was being given to "normal" healthy participants instead of the > ultimate target population, that is, persons with arthritis or some > form of inflammatory/autoimmune disease. This suggests that > it was a Phase 1 drug trial but I'd be cautious in making such > a statement because even though an American company was > supervising the trial, it apparently was doing so under British > regulatory authority (see the following article where questions > about British guidelines are raised: > http://news.bbc.co.uk/2/hi/uk_news/4815430.stm ) > > As mentioned on the www.hhs.gov website mentioned above, > Phase 1 trials typically involve only about 20-80 subjects, > a small number of subjects -- this is done to "determine the > metabolic and pharmacological actions of the drug in humans, > the side effects associated with increasing doses (to establish > a safe dose range)..." The majority of volunteers would be > involved in Phases 2-4 where targeted populations would be > recruited (e.g., for TGN1412 it might be people with arthritis) > and the main motivation for such participation is not the > payment but being able to receive a new treatment before > it is generally available -- this is particularly important to people > with conditions that have had minimal or no benefit from > standard treatments. Websites like www.clinicaltrials.gov > are recommded to these people. > > >And one wouldnt *necessarily* need > >to be desperate for money to volunteer. > > No, at least not necessarily for Phase 2-4 trials. > For example, a person with treatment resistant > depression (i.e., person who has gone through several > antidepressants and has received minimal or no benefit) > might volunteer for a clinical trial especially if the > medication (e.g., a Selective Norepinephrine Reuptake > Inhibitor or SNRI) has been somewhat effective in > the past. There are few SNRIs available (at least > in the U.S.) at this time and a clinical trial might be > the only place to get free and legal access to such > a drug. In this kind of situation, financial compensation > would take a backseat to receiving the medication as > well as the systematic monitoring of one's condition. > > For Phase 1 trials, its possible that a person would > participate because they are desperate for money > OR because one knows someone with a condition > that might benefit from a drug once it gets into a > Phase 2 trial (i.e., expediting the Phase 1 trial) OR > because one has sense of civil responsbility towards > others (such as when one donates blood) OR > any number of idiosyncratic reasons. > > I think it's a bad idea for researchers to use people > in studies only because they need the money from > participating in such studies. I think an argument > can be made on either ethical ground or on the basis > of external validity (i.e., limited generalizability of > results). > > >I heard a phone-in radio programme > >last night in which a contributor said that in the past he > >had regularly taken part in drug trials because he could > >get good money for doing so, and that someone else he > >knew had continued to do so for the same reason. > >[Note that in the Times article reproduced by Mike, Chris > >Springall of Covance Clinical Research is quoted as saying > >that side-effects were extremely rare, which is why participants > >might well think there was a very small risk for a relatively > >big reward.]. > > However, as I've pointed out above, healthy people > would probably be involved in Phase I trials and the total > number would be relatively small (things may be somewhat > different in Britain but I don't think it would be very much > different). > > And I don't doubt that there are "professional subjects", > that is, people who search out opportunities to participate > in well-paying Phase I trials (similar to people who somehow > make a "living" by selling their blood to bloodbanks). > I wouldn't be surprised if there were "social networks" of > such people who keep each other up to date on such > opportunities as well as other "research opportunities". > > Let me provide an ancedote: one day a few years back > I was sitting on bench in a park in lower Manhattan, > taking in the sunshine and fair weather. A group of > about 2-3 persons sat down on an adjacent bench > and I couldn't help overhearing part of their conversation. > One person was telling the others about this "great study" > uptown at a major university medical center where the > subjects got infusions (i.e., IV drips) of cocaine and > other drugs. At first I was doubtful that such a study > was actually being conducted until I heard more details > about it and where it was being conducted (I realzied > that such a study could be conducted at the given > location). The person who had participated in the study > explained to others who to contact, what to say, and > how to act once one got there. If memory serves me, > I believe the last things I heard before I got up and > walked away were "and then get ready for the greatest > high of your life!" > > There may be groups of individuals that make a living > from participating in research studies or "benefit" in > some way from such participation (e.g., cocaine drips). > However, if these were the only people who participated > in drug trials, I would be seriously concerned about the > results as well as the ethics involved. > > >>(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_i > d=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). > > > >It seems to me a bit early to raise this "issue" without > >any knowledge of the backgrounds of the participants. > > Well, I doubt that the companies involved will be > releasing any background about the participants, much > in the way that the drug manufacturer has "embargoed" > info about earler studies involving TGN1412. What > has been released in the press and media about the > background of the subjects should raise some concerns. > > >First, you dont need to be seriously > >poor to want to pick up a couple of thousand quid > >(see above). Second, there are plenty of poor non-minority > >people around who could do with some extra cash (not > >to mention students), so I dont see on what grounds > >coercion of ethnic minorities is relevant here. We > >simply do not know enough (or, rather, anything!)about > >the circumstances under which the participants were recruited. > > It is possible that I am "overreacting" to this situation but > I do have the concern that a number of details, ranging from > the complete results of previous animal studies to how subjects > were recruited for this particular study, will never be made > public because the companies involved will not allow them to be. > I imagine that their thinking is that "it wouldn't be prudent". > > -Mike Palij > [EMAIL PROTECTED] > New York University > > >Allen Esterson > >Former lecturer, Science Department > >Southwark College, London > >http://www.esterson.org/ --- You are currently subscribed to tips as: [email protected] To unsubscribe send a blank email to [EMAIL PROTECTED]
