Controversy Over A Glaxo Clinical Trial In Argentina
12 CommentsBy Ed Silverman // September 23rd, 2008 // 11:25 am
Maria Ester, 23, lives in a crumbling, one-room stucco cottage with her mother and daughter in Santiago del Estero, an Argentinean province northwest of Buenos Aires, according to ABC News. She had another daughter, but the 5-month-old died in May and had been one of more than 13,000 Argentinean children to participate in a Glaxo clinical trial begun last year. And Ester tells ABC News that if her infant hadn’t participated in the study Michaela would still be alive.
“Protocol Compas” is the name of the study designed to test the efficacy of Synflorix, Glaxo’s experimental pediatric pneumonia vaccine, which can also ward off the bacteria that causes meningitis and ear infections. But at least 12 babies in the trial have died over the past year in Argentina, and critics say the study uses children from poor families, who are pressured into signing consent forms (back story).
The suggestion is denied by Ricardo Ruttiman, Glaxo’s regional medical affairs and R&D director, who is responsible for “Protocol Compas” in Argentina. He tells ABC News participation is always voluntary and parents “are informed, clearly and in a language they can understand, by experienced medical investigators.” He adds they are informed of benefits, such as round-the-clock access to medical care and vaccinations against diseases, as well as risks, which he describes as few.
But Ester says a nurse’s aide her that doctors at the Eva Peron Children’s Hospital wanted to give her infant a vaccine. Ester only gave in, she says, when the nurse’s aide allegedly threatened to go to the police and have her baby taken away. “I didn’t know if the doctors, the police, the system would take her away, but I was afraid,” she tells ABC News. She found herself signing a 12-page consent form she says she couldn’t really understand, and then allowed her infant to receive a first injection.
Health-care professionals say holding clinical trials in regions with poor health-care systems can benefit everyone. Ruttiman points out that due to the high quality of care the children in the study receive, the infant mortality rate is significantly lower in those who participate in “Protocol Compas” than in those who do not, but he declined to comment on individual cases citing patient privacy.
But Ana Maria Marchesse of Eva Peron Children’s Hospital is one of several Argentinean doctors who is highly critical of the study’s methodology. She heads up the Health Professionals’ Labor Association, a group of local doctors who alerted La Federacion de Profesionals de la Salud de la Republica Argentina (the Argentinean FDA) of their concerns about possible wrongdoing.
“It’s impossible to say whether the 12 babies’ deaths are due to the vaccine or not, because half of the [total number of] children were given a placebo,” the pediatrician tells ABCNews. “But the way the study has been conducted is reprehensible.”
UPDATE: Glaxo sent us this lengthy statement later in the day: “GSK is saddened to hear of any mortality in clinical trials. Safety of patients is always our primary concern in the development of any new treatment or vaccine. It is, however, important to review such cases in the context of the rates of post-neonatal infant mortality for the country in which the trial is being conducted.Streptococcus pneumoniae is a major cause of meningitis and pneumonia in children in Latin America. More than 12 million pneumonia episodes occur each year in this region in children under five and it is estimated that at least 50,000 children die each year of pneumonia in the region (UNICEF, 2006).
“The COMPAS study is being conducted in Argentina, Panama and Colombia to measure the impact of the vaccine on these diseases…The mortality rate of children participating in the COMPAS study is closely monitored by the Independent Data Monitoring Committee and does not exceed the rate in the regions and countries participating in the study.
“GSK has extensive experience in conducting clinical studies worldwide, including in Latin America. All GSK studies are conducted according to the highest ethical and scientific standards and in compliance with international standards of Good Clinical Practice (GCP). We recognize the absolute necessity of informed consent and will only ever proceed with a trial once informed consent, in a legally and ethically acceptable form, has been obtained. Where participants are unable to give consent themselves, as is the case in the pediatric COMPAS trial, we require the informed consent of their legal guardian (usually a parent).”
An FDA Reviewer
I do not doubt that such things are occurring.
When I was in graduate school I enrolled in a drug study. I was screened out and wasn’t allowed to participate simply because I asked questions during the obtaining of informed consent.
In another trial in which I was the person obtaining the informed consent I asked the primary investigator about some serious deficencies with the consent that I believed needed to be fixed. I was then removed from working on the study.
In other cases drug companies have argued to the FDA that to change an informed consent form to be appropriately informative would not be allowed by the institutional review board (IRB). To this FDA replied that not to change it would be unethical and the sponsor should tell the IRB this.
It’s interesting that FDA has no regulatory authority to require changes in informed consent forms, the regulations only stipulate that an IRB approve it. Thus even if a drug has the potential to kill patients the FDA has no authority to require this information in the informed consent. Since many IRB’s (including academic institutions) know that to challenge a drug company on an informed consent will result in no further studies will be coming to that institution. (i.e. $). IRBs generally only rubber stamp drug company informed consent forms and will not recommend changes.
In addition due to timelines many companies only provide IRBs and regulatory agencies draft informaed consents and protocols even if regulations require final versions.
Christopher
It’s a sad story for sure. However, ABC has used two apparently biased critics as commentators and used 10 year old cases of poor compliance to illustrate its point. Fact is that increasing numbers of studies are being conducted in emerging countries for the reasons given, and in trials like this participation can offer access to better healthcare. 12 deaths so far (apparently unrelated to therapy) in a population of 13,000 is low. What is the incidence of death in a ‘normal’ population living in the conditions reported here?
My view is that companies like GSK have nothing to gain by conducting studies improperly. Seems like ABC are trying too hard to make a point.
BOB FIDDAMAN
Christiphor wrote:
“My view is that companies like GSK have nothing to gain by conducting studies improperly”
Apart from making money huh?
You are conveniently forgeting Paxil 329 study
Fid
Anon.
12 deaths in 13,000 is low (1 in 1100) ? NO WAY!!
How many deaths were there in the placebo group?
We’re talking kids getting a pneumonia vaccine. I can guarentee you that GSK would have tried to only enroll otherwise healthy kids so as to not increase the risk of finding a toxicity. They would not have enrolled kids who were so sick or emaciated in the first place that a significant number would be expected to die.
These comments are prima fascia so incredibly biased that I am highly suspicious of Chris’s claims that this was a 10 year old situation.
As for Glaxo not having anything to gain. I disagree. Glaxo has repeatedly hidden safety information on kids, and I’m talking about things that are not public, YET. In fact Glaxo hired Shirley Murphy as VP of Pediatric Marketing around 1996 and she then went to FDA where she headed up the brand new Pediatric program with her sister.
truthman30
We must remember that deaths are just “statistics” to pharmaceutical companies..
Scary..
But it’s true..
Christopher
truthman once again talks nonsense about what he ‘knows’ to be true about pharmaceutical companies. Companies of course made up of heartless, uncaring profit-oriented individuals who care nothing for the patients taking their drugs. So we’ve got that straight.
Anon says that 12 deaths in 13,000 isn’t low. The average death rate amongst healthy infants <5 years of age (live births) in Argentina is 18/1000 (UN data) and mortality from pneumonia 4-5/1000. So you tell me. The 10 year old reference was to the NIgerian (?) example raised by the ABC story, not this.
Bob and anon question why GSK wouldn’t gain by the supposed mis-management of the study, other than to make money. Well I suppose it’s a matter of perspective. How would they make money - medium to long term money from this vaccine - by deliberately taking actions by compromising the data which ultimately they weould need to support its regulatory submissions, marketing etc? It makes no commercial sense. They are not making money on this trial: It’s a means to an end and if they screw up this step there is no commercial happy ending is there?
Just my 10c worth, but I doubt that anybody with any sense in a multinational with billions of dollars at stake would deliberately risk a) the business and b) their job this way.
C
truthman30
“truthman once again talks nonsense about what he ‘knows’ to be true about pharmaceutical companies. Companies of course made up of heartless, uncaring profit-oriented individuals who care nothing for the patients taking their drugs. So we’ve got that straight”
Oh Christopher, what are you on about?
The pharmaceutical industry is up there with Big Tobacco and the Arms Industry. Everyone knows that.
Pharmaceutical companies get away with murder every day just like Big Tobacco and the arms industry. Vioxx, Zyprexa, Avandia, Paxil, need I say more?
The pharmaceutical industry is highly competitive and profit driven, you can’t deny that surely?
You also cannot deny that there is huge amount of documented negative reports of the Pharma industry’s bad behavior. One would only have to search through the web pages of Pharmalot to make that blindingly obvious!
I’m just going on what is reported and what I read about the industry, and from that perspective, it looks poorly regulated , massively biased, certainly corrupt and ethically defunct.
Christopher
Come on truthman - let’s just see a little perspective every now and then. You seem to deal with absolutes: Life’s not like that is it? Big Pharma isn’t a single entity which can characterised so sweepingly as you do. It’s not so simple but yet you maintain this constant argument - which is entertaining and insightful at times - but yet it’s the same old thing. And when you rubbish an entire industry, as you do, it’s pointless. Yes, there are documented reports of ‘bad behaviour’. They are what make the news, and Pharmalot, because as Ed has said before he looks for the tension in a story and unfortunbately as you well know, that’s what gets the coverage not the every day hum drum not very interesting matter of people doing what they hope is a decent job. To think that hordes of misdirected drones follow their evil leaders intent on damaging unthinking patients, just to bump their 401k, is wrong. So yes, I think what you wrote is nonsense but I also suspect that this won’t change a single thing. But you asked and there it is. I’d welcome a little perspective every now and then.
truthman30
Christopher ..
Although you are evidently an intelligent individual , you seem to be quite naive to the reality of what your pharmaceutical industry has actually become..
I don’t rubbish the entire industry, and as I have said before I am not anti-pharma. Of course people need access to drugs but these drugs should be safe , adequately tested and effective, but in the past decade the rampant greed emanating and encouraged by the industry itself has led to many people being harmed by dangerous and defective drugs.
Surely you have to see that an industry which claims to save lives with one hand yet harms with other is a massive and ridiculous contradiction?
Glaxo’s alleged unethical conduct in Argentina is just another example in long line of shameful practices. Pharma’s bad deeds created its bad reputation.It is a reputation ill earned. Employees of pharma should be questioning the ethics of their organizations and CEO’s instead of defensively overreacting to valid criticism from consumers, patients , activists and advocates.
Personally I couldn’t work for a company that participates in the kind of exploitation detailed in this report. But we’re all different aren’t we?…
Christopher
I don’t think I’m naive and I believe you do tend to rubbish the entire industry, consistently - and by the way it’s not my industry (I have been out of it since 1994) - but I’m not sure anybody else is interested in our respective diverging opinions so I’ll let it drop here.
Nathan
Truthman writes: “I don’t rubbish the entire industry, and as I have said before I am not anti-pharma”
Yet, Truthman also writes: “Pharmaceutical companies get away with murder every day ”
and: “The pharmaceutical industry is up there with Big Tobacco and the Arms Industry.”
Mmmm…. Something doesn’t add up here…
truthman30
Just stating fact Nathan…