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British Mishap Tests Clinical-Trial Safety

Posted on: Monday, 27 March 2006, 21:00 CST

By CHRISTINE DELL'AMORE

A clinical trial gone wrong in Britain this month has some concerned about the safety of such trials, but advocates say they are the sole vehicle for developing new treatments.

Six men in London experienced severe inflammatory reaction and multi-organ failure March 13 after they were given TGN1412, a new drug designed to treat immunological diseases. As of Sunday, one remained critically ill, and another seriously ill, at Northwick Park Hospital in London. The remaining four are in stable condition.

Clinical trials are indeed risky business, John I. Gallin, director of the National Institutes of Health's Clinical Center, told UPI. But it is essential -- the only way we can develop new medicines. It's really the core behind improving health in the world.

Clinical trials, or research studies with human volunteers, are considered the gold standard for testing new medicines and drugs. The Food and Drug Administration requires drugs and vaccines go through a clinical-trial process before approval. Many of the medications Americans rely on today went through clinical trials, such as lithium for depression, chemotherapy, and treatments for Hodgkin's disease and childhood leukemia.

But critics say the intense competition to get drugs out the door slackens standards and puts participants in danger.

Clinical trials are the key to opening the marketing door, said Vera Sharaz, president of the Alliance for Human Research Protection, a watchdog organization that monitors ethics in clinical trials and practice. Becoming a subject in a human trial is a gamble.

Gallin warned the most vital consideration when recruiting patients is informing them of the potential pitfalls of participating in a clinical trial. The subjects will then opt to sign a paper indicating they understand the risks. This is called informed consent. For instance, a patient with terminal cancer might be more willing to enter a trial than a healthy subject.

Participants should also be leery of offers of high sums of money, Gallin said. Whatever reason they may be motivated to join -- such as a family member who has a particular disease -- should trump the money reward, he added.

But that's probably not what happened in Britain, where the men were paid approximately $3,500 to participate. UPI reported last week that some consider that a form of financial coercion on the part of the researchers.

The fact they were financially in need raises a flag, Sharaz said. These are vulnerable people. It gives us a clue as to how little we value the people that are being used as human guinea pigs.

Sharaz added the issue isn't finding an alternative to clinical trials, but making them safer. There is still a widespread lack of safeguards in conducting clinical trials, with the British study as just one example, she said.

When you're testing a new drug, you'll know a lot about it before you start, but you don't know everything. That's the nature of what research is, said Marjorie Speers, executive director of the Association for the Accreditation of Human Research Protection Programs, a non-profit that ensures research institutions are responsible and ethical. So the goal in a research study is to remove unnecessary risk.

Unnecessary risk, according to Speers, includes ethical concerns such as a researcher's conflict of interest, or an inappropriate review by an institutional review board. IRBs check out the legitimacy of clinical trials before they begin.

Speers' organization conducts site visits and copious interviews before accrediting an institution.

To truly achieve a high level of compliance, organizations need to self-regulate, Speers said. Accreditation is a voluntary step.

The AAHRPP, founded in 2001, currently accredits 35 research institutions, with hundreds more going through the process.

Research through clinical trials has spiked in order to keep up with the progress of scientific findings, Gallin said. For instance, physicians used to hit cancer with a sledgehammer, but now treatment is more targeted and refined, he said.

Clinical trials are usually divided into four steps, or phases. Phase I studies are the first step after animal experiments. They usually proceed cautiously, starting with a tiny dose in one person. If nothing happens, then the dosage will be increased. In the British trial, the six men were given the drug at once -- a questionable decision, Gallin said. TeGenero, the producer of TGN1412, stated on its Web site that the drug was tested extensively in rabbits and monkeys, and extensive pre-clinical tests showed no sign of adverse effects.

Normally, if all goes well, researchers move to a Phase II trial to test efficacy. The drug is then tested in a Phase III study within a large population before it is distributed to the population.

Phase IV is post-marketing, when unexpected side effects may arise after millions of people take the drug, Gallin said. The recent example of this is the COX-2 inhibitors, such as Vioxx, which cause heart problems.

If found to be detrimental, the drug is taken off the market, as in the case of Vioxx. Researchers then figure out what caused the problem, modify it, and try again.

As for the TGN1412 trial, now shut down, investigations into what caused these egregious side effects have already begun.

E-mail: consumerhealth@upi.com

Source: United Press International

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