Main Article Content
Drug approval, drug lag, drug safety, black-box warning, Canada, United States
New drug approvals in the US and Canada were reviewed in short-term studies in the 1990s. A database of drugs approved in both countries between 1992 and 2011 exists allowing for a longer time horizon to assess trends.
To compare review times of drugs approved in the US and Canada over the 20-year period and their duration on the respective markets until any serious safety risk arose.
Data on submission and approval dates and review type were obtained from the regulatory agencies.
454 drugs were approved in both countries in the 20-year period for which the US median approval time was shorter than the Canadian median by >6 months (382 versus 574 days). Nevertheless, in 2007-11, the median approval times were closer in the two countries (302 and 356 days, respectively). 3% of the drugs
were discontinued for safety reasons in both countries. The 10-year survival rate without a serious safety warning was significantly lower in Canada (58.4%) than in the US (69.3%). Being approved in 2002-11 with a shorter review time had the greatest impact on a drug receiving a serious safety warning.
Overall, new drug approval times in the two countries in the last five years were closer, although some important differences remain so that Canadians still wait longer for some new drugs to be approved. The survival rate of a drug without a serious warning decreased substantially in the last decade in both countries, especially in drugs approved with shorter review times.
Engl J Med 2012;366:2284-93.
2. Roberts SA, Allen JD, Sigal EV. Despite criticism of the FDA review process, new cancer drugs reach patients sooner in the United States than in Europe. Health Aff
3. Moore TJ, Furberg CD. The safety risks of innovation: the FDA’s expedited drug development pathway. JAMA 2012;308:869-70.
4. Kaitin KI, Mattison N, Northington FK, Lasagna L. The drug lag: an update of the new drug introductions in the United States and in the United Kingdom, 1977 through 1987. Clin Pharmacol Ther 1989;46:121-38.
5. George CF. Atlantic crossing and drug lag. BMJ 1980;281:507-8.
6. Eastman HC. Report of the Commission of Inquiry on the Pharmaceutical Industry. Ottawa: Supply and Services Canada, 1985.
7. Nielsen Task Force. Health and Sports Program: a study team report to the Task Force on Program Review. Ottawa: Supply and Services Canada, 1985:95-109.
8. Drug Regulation. Report of the Auditor General of Canada to the House of Commons, fiscal year ending 31 March 1987. Ottawa: Supply and Services Canada, 1987.
9. Working Group on Drug Submission Review. Memorandum to the Minister (the Stein Report). Ottawa: Health and Welfare Canada, 1987.
10. Overstreet RE, Berger J, Turriff C. Program evaluation study of the Drug Safety, Quality and Efficacy Program. Ottawa: Health and Welfare Canada, 1989.
11. Gagnon D. Working in partnerships: drug review for the future. Ottawa: Health and Welfare Canada, 1992.
12. Therapeutic Products Program: baseline assessment of drug submission review process. Ottawa: Price Waterhouse Coopers, 1999.
13. Rawson NSB, Kaitin KI, Thomas KE, Perry G. Drug review in Canada: a comparison with Australia, Sweden, the United Kingdom, and the United States. Drug Inform J
14. Rawson NSB. Time required for approval of new drugs in Canada, Australia, Sweden, the United Kingdom and the United States in 1996-1998. CMAJ 2000;162:501-4.
15. Rawson NSB, Kaitin KI. New drug approval times and “therapeutic potential” in Canada, Australia, Sweden and the United States during the period 1992 to 1998. Can J Clin Pharmacol 2000;7:97-101.
16. Rawson NSB. Timeliness of review and approval of new drugs in Canada from 1999 through 2001: is progress being made? Clin Ther 2003;25:1230-47.
17. Rawson NSB, Kaitin KI. Canadian and US drug approval times and safety considerations. Ann Pharmacother 2003;37:1403-8.
18. Health Canada’s proposal to Parliament for user fees and service standards for human drugs and medical devices programs. Ottawa: Health Canada, 2010. http://www.hcsc.gc.ca/dhpmps/alt_formats/pdf/finance/costs-couts/feepropo-frais-eng.pdf (January 20, 2013).
19. Paul D. Comparison of the drug approval processes in the US, the EU and Canada. Int J Med Marketing 2001;1:224-35.
20. Davidson MH. Controversy surrounding the safety of cerivastatin. Expert Opin Drug Saf 2002;1:207-12.
21. Lessons from cisapride. CMAJ 2001;164:1269.
22. Kondro W. Canada needs better drug reporting, says inquest. Lancet 2001;357:1424.
23. Sibbald B. Cisapride, before and after: still waiting for ADE-reporting reform. CMAJ 2001;165:1370.
24. Graham DJ, Drinkard CR, Shatin D. Incidence of idiopathic acute liver failure and hospitalized liver injury in patients treated with troglitazone. Am J Gastroenterol 2003;98:175-9.
25. Kondro W. Law suits mount in the wake of rofecoxib (Vioxx) withdrawal. CMAJ 2004;171:1335.
26. Drug and Biologic Approval Reports. Silver Spring, MD: Food and Drug Administration, 2012. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/default.htm (January 20, 2013).
27. Medicines in development. Washington, DC: Pharmaceutical Research and Manufacturers of America, 2012. http://www.phrma.org/research/newmedicines (January 20, 2013).
28. Drug submission performance reports. Ottawa: Health Canada, 2012. http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applicdemande/docs/perform-rendement/indexeng.php (January 20, 2013).
29. Drugs@FDA. Silver Spring, MD: Food and Drug Administration, 2012. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ (January 20, 2013).
30. Drug product database online query. Ottawa: Health Canada, 2012. http://webprod5.hcsc.gc.ca/dpd-bdpp/index-eng.jsp (January 20, 2013).
31. Issa AM, Phillips KA, Van Bebber S, et al. Drug withdrawals in the United States: a systematic review of the evidence and analysis of trends. Curr Drug Saf 2007;2:177-85.
32. Lexchin J. Drug withdrawals from the Canadian market for safety reasons, 1963- 2004. CMAJ 2005;172:765-7.
33. Begosh A, Goldsmith J, Hass E, Lutter RW, Nardinelli C, Vernon JA. Black box warnings and drug safety: examining the determinants and timing of FDA warning labels. NBER Working Paper No. 12803. Cambridge, MA: National Bureau of Economic Research, 2006. http://www.nber.org/papers/w12803 (January 20, 2013).
34. Murphy S, Roberts R. “Black box” 101: how the Food and Drug Administration evaluates, communicates, and manages drug benefit/risk. J Allergy Clin Immunol 2006;117:34-9.
35. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA
36. MedWatch: the FDA safety information and adverse event reporting program. Silver Spring, MD: Food and Drug Administration, 2013. http://www.fda.gov/Safety/MedWatch/default.htm (January 20, 2013).
37. Kelly L, Lazzaro M, Petersen C. Canadian drug regulatory framework. Can J Neurol Sci 2007;34(suppl 1):S3-10.
38. MedEffect Canada. Ottawa: Health Canada, 2013. http://www.hc-sc.gc.ca/dhpmps/medeff/index-eng.php (January 20, 2013).
39. Kondro W. Drug approvals taking too long? CMAJ 2002;166:790.
40. Rawson NSB. Human resources for the approval of new drugs in Canada, Australia, Sweden, the United Kingdom and the United States. Can J Clin Pharmacol 2002;9:73-8.
41. Rawson NSB. Access to new oncology drugs in Canada compared with the United States and Europe. Vancouver: Fraser Institute, 2012. http://www.fraserinstitute.org/researchnews/display.aspx?id=18744 (January 20, 2013).
42. Drug Trend Quarterly Spotlight 3. St. Louis, MO: Express Scripts Research and New Solutions Lab, 2012. http://digital.turnpage.com/i/95262 (January 20, 2013).
43. Philipson TJ, Sun E. Cost of caution: the impact on patients of delayed drug approvals. FDA Project Report 2. Manhattan Institute, New York: Manhattan Institute, 2010. http://www.manhattaninstitute.org/html/fda_02.htm (January 20, 2013).
44. Lexchin J. New drugs and safety: what happened to new active substances approved in Canada between 1995 and 2010? Arch Intern Med 2012;172:1680-1.
45. About BMC. Toronto: Best Medicines Coalition, 2009. http://www.bestmedicines.ca/about (January 20, 2013).
46. Rawson NSB. Assessing prescription medications for priority regulatory review. Regul Toxicol Pharmacol 2005;42:70-6.
47. Milne CP, Kaitin KI. FDA review divisions: performance levels and the impact on drug sponsors. Clin Pharmacol Ther 2012;91:393- 404.
48. Berlin RJ. Examination of the relationship between oncology drug labeling revision frequency and FDA product categorization. Am J Public Health 2009;99:1693-8.
49. Young T. Presentation before the Standing Senate Committee on Social Affairs, Science and Technology Evidence. Ottawa: Parliament of Canada, 2012.
http://www.parl.gc.ca/content/sen/committee/411/soci/49733-e.htm (January 20, 2013).