Healthy Skepticism Library item: 13473

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Publication type: news

Boseley S.
Pharma firms end drug trials early in rush to beat rivals, say experts
The Guardian 2008 Apr 9
http://www.guardian.co.uk/society/2008/apr/09/health.pharmaceuticals

Full text:

· Study covered well-known cancer treatments
· Full period ‘necessary to show benefits and risks’

The real benefit of some cancer drugs may be exaggerated because of a growing tendency for firms and investigators to call a premature halt to trials the moment a benefit appears, experts warn today.

Italian researchers writing in the cancer journal Annals of Oncology reveal a dramatic increase in the number of studies terminated early. They claim that in some cases drug companies are rushing with early, incomplete results to the licensing authorities. One reason, the researchers suggest, is a desire to get their drugs on the market ahead of their competitors.

Among 14 of these early results published between 2005 and 2007, 11 were used to support a licence application.

“This suggests a commercial component in stopping trials prematurely. In fact, this strategy could guarantee quicker access to the market for companies,” said one of the authors, Dr Giovanni Apolone from the Mario Negri Institute for Pharmacological Research in Milan.

Without the complete information gathered from a full-length trial, he says, it is not certain that a drug is both as effective as the investigators say, and safe in the long term. It can take years for the adverse effects of a drug to come out. The 25 prematurely halted trials in the study lasted, on average, for 30 months.

Professor Stuart Pocock, professor of medical statistics at the London School of Hygiene and Tropical Medicine, said there was “an underlying bias towards exaggeration in a trial that stops early”. He cited as an example the trials of one of the earliest Aids drugs, AZT. In the United States trials of AZT were stopped early when it appeared that people with HIV were doing well. But the European arm of the trials “went on much longer and showed nothing like the same breakthrough”, he said. “That’s why they decided they needed multi-drug therapy.”

Among the drug trials that have been stopped early are those of well-known drugs heralded as breakthroughs, such as Herceptin (trastuzumab) and Tyverb (lapatinib) for breast cancer and Avastin (bevacizumab) for bowel and renal cancer.

The quality of drug trials had risen enormously in the past 20 years, said Professor David Kerr, editor in chief of the journal, but he added: “Interpreting trials that have been stopped prematurely must be done with caution.”

He and the other experts said trials should not often be stopped early – the ethical duty to give all patients in the trial the drug that is working best should not override the duty to the public at large to obtain better long-term data on how well and how safely the drug works. “We, as scientists, put a great deal of work and effort into designing appropriate clinical trials, and in all but the rarest of cases we should not rush to abandon those designs in the face of early signs of benefit,” he said.

The Italian group analysed 25 randomised controlled trials of cancer drugs that had been stopped early after showing some benefit to patients in the years between 1997 and 2007. More than half of them were stopped in the past three years. Five of them had enrolled less than 40% of the target number of patients. “It is obvious that the risk of overestimating treatment effects increases markedly when the sample is small,” they write.

They recommend that an independent board of scientists should make the decision to stop a trial or continue. Professor Kerr called for transparency from the drug companies, saying they should publish the protocol for every trial.

The Association of the British Pharmaceutical Industry (ABPI) denied there was an issue. “On the rare occasions that a trial is stopped it is done with the primary purpose of getting a medicine to patients as quickly as possible,” said spokesman Richard Ley.

“That’s particularly true with oncology products, where a patient may be desperately or terminally ill.”