Therapeutics Initiative--role and function

Recent articles in the press and the BCMJ have made it clear that the UBC Therapeutics Ini tiative (TI) has inadequately communicated its role and function to the medical profession. The following represents a first step in correcting that deficiency.

The TI was established in 1994 through a grant to UBC from the Ministry of Health, in order to provide a stable, ongoing resource for evaluating pharmaceuticals and to offer continuing education in relation to drug therapy.

Each year we publish a number of Therapeutics Letters about relevant care issues and distribute them to more than 12 000 practising physicians and pharmacists throughout BC and ap proximately 1000 other stakeholders and out-of-province subscribers. Elec tronic versions are available on our web site at www.ti.ubc.ca, which receives several million visits a year.

For many years an annual 2-day drug therapy course has been offered. The course is highly interactive and covers both common and new drug therapy issues from an evidence-based perspective. The course does not receive any sponsorship from the drug industry.

Every year the TI also offers a number of community educational sessions around BC, ranging from 1-hour CME rounds to 1-day courses. The main purpose of these is to provide an introduction to evidence-based health care. In addition, there is an attempt to disseminate and discuss research findings and relate these findings to patient-specific drug therapy–decision-making.

Upon request, the TI carries out evaluations of specific drugs for PharmaCare with the understanding that our reports will be used as one of a number of information resources when PharmaCare makes their coverage decisions. The TI is not involved in funding decisions, nor have we ever considered drug costs as part of our evaluation.

PharmaCare requests these reviews because Health Canada does not consider whether new drugs provide a therapeutic advantage compared with existing alternatives. To obtain a licence for marketing, a manufacturer needs only to provide evidence of adequate safety, efficacy, and product quality. Efficacy is often based on surrogate measures, not patient outcomes. Safety testing includes laboratory and animal studies as well as pre-licensing clinical trials, during which relatively small numbers of people are exposed to a drug, typically for periods ranging from a few days to a maximum of 1 to 2 years. Clinical trials usually compare a drug’s effects with placebo, rather than other drug treatments.

The TI uses a standardized systematic review methodology. This includes a replicable search of computerized bibliographic databases (Med line, EMBASE, Cochrane Database of Systematic Reviews, Web of Science) as well as the drug reviews that are posted on the US FDA’s web site and the manufacturer’s submission to PharmaCare. The goal is to en sure that these reviews are based on all available randomized trials. A multidisciplinary working group, including pharmacologists, physicians, pharmacists, epidemiologists, and a biostatistician, assists with each review.

A condition-specific list of outcomes of importance to patients is developed for each review. These include mortality and serious morbidity, hospitalization rates, rates of disease complications, symptom severity, quality of life, etc. We rank outcomes within a standard hierarchy and at tribute the most weight to those with the greatest clinical importance. Unvalidated surrogate outcomes, such as biochemical, radiological, or blood pressure measurements, are usually ranked lower in the hierarchy than effects with a discernable effect on patients’ lives.

For all but the simplest drug evaluations, the Therapeutics Initiative requests peer review from local and international clinical and methodological experts. Before the drug assessment report is sent to PharmaCare, we present a summary to the Therapeutics Initiative’s Scientific Information and Educational Committee (SIEC). This committee consists of family practice and specialist physicians from the UBC Faculty of Medicine and community practice, as well as academic and hospital-based pharmacists, and includes two physicians nominated by the BCMA—one physician nominated by the BC College of Family Practice and one pharmacist nominated by the BC College of Pharmacists. The SIEC can request additional information, challenge content or conclusions, and recommend changes before approving or rejecting a drug assessment. Our final conclusions are concerned with the observed beneficial and harmful effects of a drug in randomized controlled trials and specifically address whether evidence exists of a clinical advantage when compared with alternatives available in Canada.

This process would be more transparent if the pharmaceutical industry could overcome its concerns over confidentiality of unpublished studies. At present, if the TI uses these data, we are bound by both the federal and provincial governments’ agreements to respect the manufacturer’s desire for commercial confidentiality.

Drug safety and effectiveness are public concerns, so British Columbians should have the right to complete information, not just the subset of studies or outcomes that a company decides to make public. We also believe that Health Canada reviewers’ evaluation reports should be publicly available, in addition to the full reports of unpublished pre-market clinical trials and pre-clinical data.

Post-market studies are needed to complement the standard pre-market evaluation of new drugs. Currently, post-market drug safety and effectiveness monitoring is a federal responsibility (Marketed Health Products Directorate of Health Canada), but the funds and staff allocated to this activity at the national level are inadequate.

Provincial governments, including the BC, Ontario, and Quebec Ministries of Health, have begun to allocate more resources to post-market research, using linked administrative health and prescribing databases. British Columbia is in an ideal position to carry out such research, given the complete prescription database available through PharmaNet.

—Ken Bassett, MD 
Acting Director, Therapeutics Initiative, UBC