January 29, 1999

Research ethics 101

With government funding of medical research falling seriously behind our competitors in the United States, the call of private money is a powerful one. Who can blame a university researcher for actively courting industry these days, especially when a company appears to have not only deep pockets but also a genuine interest in forging a working partnership?

As Dr. Joel Weiner, associate dean of medicine and dentistry (research), pointed out in a Folio article recently, such partnerships often result in the most dramatic breakthroughs of our time. Dr. Lorne Tyrrell's hepatitis B drug, for instance, was supported largely by the Glaxo Wellcome Heritage Research Institute, and there are countless other successful research contracts at the University of Alberta.

But what happens when a partnership doesn't run so smoothly, when corporations exert an influence not only in violation of the principles of academic freedom, but which might actually put human test subjects at risk? The example on everyone's mind lately is the Dr. Nancy Olivieri case at the Hospital for Sick Children in Toronto.

Without formal approval from the hospital, Olivieri signed a contract with the pharmaceutical company Apotex Inc. to run clinical trials for a drug called L1 or deferiprone. When she later discovered the drug may have harmful side effects, Apotex tried to prevent her from publishing the results. Olivieri's research team, the hospital and Apotex became embroiled in a complicated legal battle, with the players pointing fingers of blame at everyone but themselves.

Perhaps the most disturbing finding, however, of an independent review panel headed by Dr. Arnold Naimark of the University of Manitoba, was the case could not be dismissed as an exception to the rule, or simply the result of a bad mix of volatile personalities. The review found there may be "lessons for other institutions facing similar challenges."

At the University of Alberta, with more than 1,000 active clinical trials, administrators like Weiner are, for the most part, confident we have one of the finest ethics review processes in Canadian academia. But no matter how seemingly foolproof your protocol, there are no absolute guarantees against a researcher going astray, admits Dr. Ron Kratochvil, senior adviser for the vice-president (research and external affairs).

"You always have the possibility that a researcher may go ahead and do something without carrying out all the proper safeguards," says Kratochvil. "All we can do is when we learn about it, try to clean up ... If they have done something that's in violation of the regulations then we can take disciplinary action, but that's after the fact."

While Kratochvil says he is not aware of any serious ethical breaches among researchers at the U of A in recent years, policy co-ordinator and ethics committee chairman Dr. Mike Enzle says examples do exist "but they precede current time."

"I've reviewed thousands of proposals for research, and I've only seen two in my entire career where I thought the individual meant to perform unethical acts that would put subjects at unreasonable risks," says Enzle. He says those cases were more than 20 years ago, and as far as he knows, "the researchers did not look for another venue" after the projects were rejected by the ethics board.

In Enzle's view, there are enough checks and balances at the U of A to sort out any potential problems before research hits clinical trials. But he stresses the principal reason for an ethics board is not to play the heavy. Board members are there to help researchers see potential problems they may not have considered in designing an experiment, not to pass judgements of character.

"Where ethical problems come from typically are unseen consequences of otherwise benign acts," he says. "We hardly ever do see big flamboyant departures from good ethical treatment of human participants. Don't get me wrong, I'm not saying everything's fine. While 99 per cent of proposals end up being fine, it's not that percentage that don't need work. There are important issues that come up but they're unintended."

In addition to approval by a faculty ethics review committee, any project involving an industry partner has to pass through a resource allocation process and a contract review. For the university not to sign off on a contract between a researcher and a corporate investor, as happened in Olivieri's case, would simply never happen, says Weiner, at least not in his faculty. And the university would never agree to a confidentiality clause, he says, since its policy governing clinical trials clearly mandates "final analysis and interpretation of [resultant data] remain with the researchers" and it is the "researchers' duty to disseminate the analysis and interpretation of their results to the research community." Critical of media reports casting Olivieri as an unblemished champion of academic freedom, Weiner says the Naimark review demonstrates "there was blame on both sides."

"Clearly the hospital didn't enforce the regulations the way they should have. They didn't inform people that things existed the way they should have," says Weiner. But the review also found Olivieri in conflict of interest stating: "Policies on reporting external professional activities [in her department] appear to have been widely ignored."

"She did not get the university or the hospital to sign off on her contract which we would not allow here," says Weiner. "She did not inform the ethics committee of problems until a year later which we would not allow here."

However both Dr. Bill McBlain, associate vice-president (research), and Enzle argue casting pharmaceutical companies as the scapegoat in this scenario would be unfair, since most companies are as vigilant about proper ethical procedure as one could hope.

"Almost all companies are interested in getting the right results from their research," says McBlain, "and they are definitely interested in protecting their patients. They design the studies carefully. They make sure the information sheet and consent form for the patient are designed as well as they can, and they work with the researchers to get it approved by the local research ethics board...We had one trial that didn't start here because there were some adverse events reported at other institutions, transmitted to us by the drug company. They were conscientious."

The bottom line, says McBlain, is regulations are only as good as people's knowledge of them. Pleading ignorance is no excuse, since every faculty has a policy clearly laid out.

Enzle agrees: "Ethics should always be on our minds as we're doing research, not the last thing we think of."

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