British Columbia’s health authorities have formed a single BC Health Authorities Pharmacy and Therapeutics (BCHA P&T) Committee to make recommendations regarding drugs that will become or not become part of your hospital’s formulary. Because there is now only one body for all hospitals in BC, the recommendations of BCHA P&T affect all physicians who practise in BC hospitals.
Recently BCHA P&T has recommended against adding dabigatran, prasugrel, and ticagrelor[1-3] to the formulary on the basis of “insufficient evidence [this drug] leads to an overall net benefit to patients.” But it is the methodology utilized by BCHA P&T that leads them to these conclusions. In their reviews of these drugs they use a “hierarchy of health outcomes” that starts with all-cause mortality, followed by (total) serious adverse events (SAE) and only after that the primary outcome(s) of the studies that they reviewed.
Few single clinical trials are powered to demonstrate a difference in all-cause mortality, so this outcome is almost guaranteed to produce a type II error. Similarly, the use of total SAE as a clinical outcome, rather than as a marker of safety, is almost guaranteed to produce a type II error. This misuse of SAE data by the Therapeutics Initiative (TI) was discussed in 2005 by Dr Karin Humphries and me. Unfortunately this misuse of SAE data continues to appear in publications by the TI.[5-7] Also, the statistical analyses performed by BCHA P&T on dabigatran1 are remarkably similar to the latter publication by the TI.
The reviews completed by the Common Drug Review of dabigatran, prasugrel, and ticagrelor[8-10] do not use SAE as part of their evaluation, although only dabigatran was recommended for listing and only then “with criteria/condition.”
Authors affiliated with the Therapeutics Initiative do not believe that their methodology is flawed or atypical and continue to publish its merits. And now their methodology is being used by BCHA P&T to keep what might be useful drugs out of your hospital. Why then does the TI and BCHA P&T use total SAE as a marker of what they call “net health benefit” and “overall net benefit?”[1-3] I believe that it is because part of the role of the TI and the BCHA P&T is to discourage the use of newer—and often more expensive—medications in your office or hospital.
Unfortunately the arguments made by Dr Humphries and me4 could be ignored by those two groups because they are accountable only to the Ministry of Health and the BCHA who ultimately fund both bodies and who have a vested interest in perpetuating a methodology that Dr Humphries and I predicted had the potential to do more harm than good. We seem to have been correct.
—David Miller, MD
1. BC Health Authorities P&T Formulary Drug Review: Dabigatran.
2. BC Health Authorities P&T Formulary Drug Review: Prasugrel.
3. BC Health Authorities P&T Formulary Drug Review: Ticagrelor.
4. Miller DB, Humphries KH. A new way to evaluate randomized controlled trials? New approach does more harm than good. BCMJ 2005;47:241-244.
5. Therapeutics Initiative. A Systematic Review of the Efficacy of Bisphosphonates. Therapeutics Letter 2011;83. Accessed 31 July 2012. www.ti.ubc.ca/letter83.
6. Therapeutics Initiative. Do statins have a role in primary prevention? An update. Therapeutics Letter 2010;77. Accessed 31 July 2012. www.ti.ubc.ca/letter77.
7. Therapeutics Initiative. Dabigatran for atrial fibrillation: Why we cannot rely on RE-LY. Therapeutics Letter 2011;80. Accessed 31 July 2012. www.ti.ubc.ca/letter80.
8. Common Drug Review. CEDAC final recommendation. Dabigatran. Accessed 31 July 2012. www.cadth.ca/media/cdr/complete/cdr_complete_Pradax_June-27-11.pdf.
9. Common Drug Review. CEDAC final recommendation. Prasugrel. Accessed 31 July 2012. www.cadth.ca/media/cdr/complete/cdr_complete_Effient-Feb-18-2011.pdf.
10. Common drug Review. CEDAC final recommendation. Ticagrelor. Accessed 31 July 2012. www.cadth.ca/media/cdr/complete/cdr_complete_Brilinta_Dec-20-11.pdf.
11. Bassett K, Chambers K, McCormack J, et al. Accounting for serious adverse events. BCMJ 2005;47:531-531.
12. Tejani AM, Musini V, Bassett K, et al. Statins for primary prevention. CMAJ 2012;184:791.
Above is the information needed to cite this article in your paper or presentation. The International Committee
of Medical Journal Editors (ICMJE) recommends the following citation style, which is the now nearly universally
accepted citation style for scientific papers:
Halpern SD, Ubel PA, Caplan AL, Marion DW, Palmer AM, Schiding JK, et al. Solid-organ transplantation in HIV-infected patients. N Engl J Med. 2002;347:284-7.
About the ICMJE and citation styles
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