Author: Jon Merz
Date: 04-07-06 17:15
Guarding the human guinea pigs
http://www.latimes.com/news/opinion/commentary/la-oe-abramson7apr07,1,1933114.story?ctrack=1&cset=true
Los Angeles Times April 7, 2006 Friday
April 7, 2006 Friday
SECTION: CALIFORNIA; Metro; Editorial Pages Desk; Part B; Pg. 11
BYLINE: John Abramson, JOHN ABRAMSON, a clinical instructor at Harvard
Medical School, is the author of "Overdosed America."
MINUTES after the first of six human volunteers was injected with an
experimental, genetically engineered drug in London last month, the men
one by one began screaming in pain, tearing their clothes off,
convulsing and losing consciousness, according to media reports.
In an interview with Britain's Daily Mirror, Nino Abdelhady, 28, who
said he was offered $3,500 to participate in the study, recalled feeling
the drug "ripping through" his body "like wildfire." His head reportedly
swelled to more than twice its normal size, and he didn't regain
consciousness for eight days. Other volunteers suffered organ failure,
and one remains hospitalized, according to the Associated Press.
Unexpected things happen in medical research, especially when a drug is
administered to humans for the first time. Eighty percent of the drugs
tested on humans in the U.S. never win Food and Drug Administration
approval. Still, there are several clues that the tragedy in London
could have been minimized or averted -- and more clues that a similar
disaster could happen in the U.S. So the cautionary tale of the
experimental drug called TGN1412 deserves intense scrutiny on both sides
of the Atlantic.
Developed by the German company TeGenero, TGN1412 is an antibody
manufactured by fusing mouse and human cells. It was designed to
activate one part of the immune system specifically to attack another.
TeGenero hoped it would revolutionize therapies for diseases involving
the immune system, such as some types of leukemia, multiple sclerosis
and rheumatoid arthritis.
The company applied in Germany for permission to administer tiny doses
(one five-hundredth of the proposed therapeutic dose) to human
volunteers, but was rejected. It then received permission to do the
study in Britain.
Two of the volunteers told British reporters that they were warned to
expect only headaches and nausea, and had no idea that monkeys given
TGN1412 had developed swelling of the immune tissue in their necks.
Inexplicably, rather than giving the drug to one man at a time and
waiting to rule out any untoward reaction, the six men were injected at
10-minute intervals, according to the Daily Mirror. Waiting a day or two
would have been more prudent for a new biotech drug. A company
spokeswoman Thursday would not comment on the dosing interval.
Abdelhady told the Daily Mirror that by the time he got the drug, the
first volunteers were already sick and a man next to him, who had been
given a dose minutes earlier, was complaining of head pain, "like
rockets going off" -- but that the experiment continued anyway.
British regulators said they found no evidence of drug contamination or
improper practices, and that the tiny doses should not have caused such
a reaction. The investigation is continuing.
But the fact that three weeks later British officials still don't know
what went wrong should raise alarms here as well. That's because
although the study involved a German drug in London, it was carried out
by Parexel International, a U.S. research company based outside Boston.
Parexel's website boasts that it partners with drug and biotech
companies "to accelerate time-to-market, control development costs,
reduce risk and maximize return on investment." (The London study might
have achieved all of these goals, except, of course, reducing risk.)
In the United States, "institutional review boards" are entrusted with
responsibility for overseeing the safety of human volunteers in drug
studies. The government established these boards to prevent a repetition
of the U.S. Public Health Service's disgraceful "Tuskegee Study of
Untreated Syphilis in the Negro Male," in which poor black sharecroppers
were not told they had syphilis so that the disease's horrific effects
could be studied over the next 40 years.
When the institutional review boards were created, most medical research
was conducted by universities and nonprofit institutions. Now most
clinical research is done by for-profit research companies such as
Parexel. Similarly, oversight of the safety of human volunteers in most
U.S. studies is no longer done by nonprofit IRBs, but by for-profit
review companies, hired directly by the for-profit research companies.
The U.S. government approves of this -- but I believe this system lacks
the appropriate checks and balances to protect human volunteers.
According to Bloomberg News, the largest for-profit IRB in the U.S.
oversees 17,000 studies on people, yet can spend as little as four
minutes a study to evaluate whether volunteers are adequately protected.
And if one for-profit ethics board doesn't approve a study, nothing
stops the company from simply applying to another -- like TeGenero
moving its study from Germany to Britain. In 1998, the inspector general
of the U.S. Department of Health and Human Services recommended rules to
stop this practice, known as "IRB-shopping." Ironically, just two months
before the London disaster, the FDA decided that such rules were not
necessary.
Moreover, the FDA recently approved "phase 0 studies" in which human
beings can be given minuscule doses of experimental drugs even before
animal studies are completed. Sen. Charles Grassley (R-Iowa) recently
told the journal Nature that just when more oversight is needed, "the
FDA is loosening the reins on drug companies. I'm concerned for those
who will be receiving these experimental drugs."
The issue isn't simply whether the research is commercially sponsored
(after all, the grotesque Tuskegee study was not for-profit), but
whether there are adequate safeguards to make sure that human volunteers
are not exposed to unnecessary risks, that studies are carried out as
designed and that results are accurately reported.
Unfortunately, these watchdog functions are being eroded. The
entrepreneurial incentive to develop new drug therapies is a great
motivator. But it will not serve the greater good unless and until there
is independent, noncommercial oversight of medical research.
Copyright Los Angeles Times 2006
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