Background:  

There have been gradual changes in evaluation processes for premarket evaluation of medical products such as drugs, biologics and medical devices. Early release of uncharacterized investigational products for human trials and premature commercialization of deficient technologies have resulted in morbidity and unnecessary costs to the public. The changes came in the late-eighties during deregulation introduced by the Progressive Conservative government but did not appear in public documents until about 1990. Very few have a legislative basis. They reflect a drift towards ad hoc regulation. Such an environment is propitious for corrupt practices and influence peddling. It also increases risks of adverse reactions amongst vulnerable populations. Public health aspects and health care insurance costs have not been appraised. 

Issues: 

Ad hoc review of an AIDS therapeutic (Viramune™, Nevirapine Boeringher Ingleheim) preceded the formal release of the drug in the mid-nineties. There were three previous refusals of the New Drug Submission (NDS) by evaluators at Health Canada (HC). There had been abuses in the distribution of the drug through the Compassionate Access provision of the regulations. Formal release for clinical trial succeeded when HC management delegated the decision to an external review committee. In spite of severe adverse reactions and questionable efficacy, the committee ruled favourably. Conflicts of interest within the committee membership and political pressure surround the case.  

Ad hoc or conditional approval for general marketing took place recently with a viral flu drug (Relenza™, GlaxoWellcome). The product was conditionally authorized by HC, overruling its evaluators' assessment, in spite of U.S. and U.K. controversy on its safety and usefulness. An aura of secrecy surrounds early studies. The product is presently sold under an approval process which demands ongoing studies to demonstrate safety and efficacy. It is tantamount to the clinical trial of a widely prescribed drug as part of a multi-million dollar commercial promotion. Sponsors have not publicly disclosed the peculiarities of HC's conditional approval. 

Peripheral Issues: 

Accelerated review or 'fast-tracking' of health care products has been employed by HC for about ten years. Rationalized on the basis of 'urgent' need and absence of 'alternative' therapies, it is increasingly frequent and relies on downgraded criteria of safety and efficacy. It is often employed when sponsors are large multi-nationals or when vocal lobbies are involved surrounding controversial products. There is no authority under Food and Drug legislation for fast-tracking or conditional approval.  

Availability of data from clinical trials depends on forthright reporting of trial results. Fast-tracking is predicated on the basis of continuous flow of information as the trial progresses. In practice, adverse reactions encountered during clinical trials are rarely reported in a timely fashion. Forthright information from clinical trials has become increasingly difficult to obtain from investigators. Fear of litigation, conflicts of interest and confidentiality agreements between investigators and sponsors impede disclosure of problems to regulatory agencies.

Even in situations where the investigators' ethics prevail, there is coercion and suppression of adverse information in the context of clinical trials and commercial development. The processes of suppression include interference with publications, lawsuits, injunctions and even threats of physical violence. To expect timely disclosure of problems incidental to clinical trials authorized under fast-tracking is both naive and utopian. 

Promotion of new technologies disguised as medical news creates demand for uncharacterized products by the general public. The process is used to stimulate marketing of what is at best investigational, and at worst fraudulent or hazardous. Specialty AIDS therapy is widely promoted through informal channels and the products are often available through illicit distribution before clinical trials are formally authorized. This mechanism is used to pressure HC into fast-tracking or devolution of policies to sham external review committees. 

Policy Options: 

The Minister of Health must place the health of Canadians above commercial gains and government tax income. Clinical trials of dubious merit conducted on a profit basis have a poor success history. They cannot be justified in a subsidized health insurance environment.