THE RISE AND FALL OF THE THIAZOLIDINEDIONES: IMPACT OF CLINICAL EVIDENCE PUBLICATION AND FORMULARY CHANGE ON THE PRESCRIPTION INCIDENCE OF THIAZOLIDINEDIONES

Main Article Content

Salman Hashim
Tara Gomes
David Juurlink
Chelsea Hellings
Muhammad Mamdani

Keywords

Diabetes, drug utilization, drug policy, pharmacoepidemiology

Abstract

Background
Numerous factors affect drug utilization including clinical trials, promotional activity, drug safety signals and funding practices. We sought to investigate the impact of cardiovascular safety concerns and public drug formulary restrictions on the use of the thiazolidinediones (TZDs): rosiglitazone and pioglitazone.


Methods
We conducted a population-based cross-sectional time series analysis among more than 1.6 million older residents of Ontario, Canada using administrative healthcare claims databases from January 2000 to September 2010 to examine the impact of two events on the rate of initiation of TZDs among those aged
66 years and older: 1) the publication of a prominent meta-analysis suggesting cardiovascular harm for rosiglitazone, and 2) the introduction of prescribing restrictions for TZDs on the public formulary.


Results
Incident rosiglitazone prescribing decreased significantly from 5.32 to 0.44 prescriptions per 1,000 patients in the quarter following the publication of a meta-analysis, suggesting safety concerns for rosiglitazone (p<0.01). Similarly, incident pioglitazone prescribing continued to decline from 1.89 just prior to the publication of the meta-analysis to 0.53 prescriptions per 1,000 patients just prior to the policy implementation (p<0.01). Following the implementation of formulary restrictions for TZDs in Q2 of 2009, the rate of incident prescriptions for rosiglitazone fell further, from 0.20 prescriptions per 1,000 patients in the preceding quarter to 0.03 prescriptions per 1,000 patients in the subsequent quarter (Q3 of 2009; p<0.01). The rate of prescriptions dispensed for pioglitazone also decreased from 0.53 in Q1of 2009 to 0.11 prescriptions per 1,000 patients in Q3 of 2009 (p <0.01).


Conclusion
Both the publication of clinical evidence and drug policy changes can significantly influence the utilization of the TZDs.

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References

1. Stafford RS, Furberg CD, Finkelstein SN, Cockburn IM, Alehegn T, Ma J. Impact of clinical trial results on national trends in ablocker prescribing, 1996–2002. JAMA
2004;291(1):54-62.
2. Goldman DP, Joyce GF, Zheng Y. Prescription drug cost sharing: associations with medication and medical utilization and spending and health. JAMA 2007;298.1:61-69.
3. Hollon MF. Direct-to-consumer marketing of prescription drugs. JAMA 1999;281.4:382-384.
4. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspectivepioglitAzone Clinical Trial In macroVascular Events): a randomized controlled trial. The Lancet 2005;366:1279-1289.
5. Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006;355:2427-2443.
6. Hernandez AV, Usmani A, Rajamanickam A, Moheet A. Thiazolidinediones and risk of heart failure in patients with or at high risk of type 2 diabetes mellitus: a meta-analysis and metaregression analysis of placebo-controlled randomized clinical trials. Am J Cardiovasc Drugs 2011;11(2):115-128.
7. Shah ND, Montori VM, Krumholz HM, Tu K, Alexander C, Jackevicius CA. Responding to an FDA warning- geographic variation in the use of rosiglitazone. N Engl J Med 2010;363:2081-2084.
8. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356:2457-2471.
9. US Department of Health and Human Services: US Food and Drug Administration: FDA significantly restricts access to the diabetes drug Avandia [article online], 2010. Available from: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm226956.htm Accessed 30 March 2011
10. European Medicines Agency: Questions and answers on the suspension of rosiglitazonecontaining medicines, Sept 2010. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2010/09/WC500097003.pdf
11. Ministry of Health and Long-Term Care: Change in Funding Status Rosiglitazone (Avandia®) and Pioglitazone (Actos® and Generics). Ontario Public Drug Programs.
12. Ministry of Health and Long-Term Care. Exceptional Access Program, Telephone Request Service: Reimbursement Criteria, Sept 2011. Available from: http://www.health.gov.on.ca/english/public/pub/drugs/trs/trs_guide.pdf
13. Starner CI, Schafer JA, Heaton AH, Gleason PP. Rosiglitazone and pioglitazone utilization from January 2007 through May 2008 associated with five risk-warning events. J Manag Care Pharm 2008; Jul-Aug;14(6):523-31.
14. Stewart KA, Natzke BM, Williams T, Granger E, Casscells SW, Croghan TW. Temporal trends in anti-diabetes drug use in TRICARE following safety warnings in 2007 about rosiglitazone. Pharmacoepidemiol Drug Saf 2009 Nov;18(11):1048-52.
15. Shi L, Zhao Y, Szymanski K, Yau L, Fonseca V. Impact of thiazolidinedione safety warnings on medication use patterns and glycemic control among veterans with diabetes mellitus. J Diabetes Complications 2011;May-Jun 25(3):143-50.
16. Jain R, Mullins CD, Lee H, Wong W. Use of rosiglitazone and pioglitazone immediately after the cardiovascular risk warnings. Res Social Adm Pharm 2012 Jan;8(1):47-59.
17. Morrow RL, Carney G, Wright JM, Bassett K, Sutherland J, Dormuth CR. Impact of rosiglitazone meta-analysis on use of glucoselowering medications. Open Med
2010;4(1):e50-9.
18. Shah ND, Montori VM, Krumholz HM, Tu K, Alexander GC, Jackevicius CA. Responding to an FDA warning--geographic variation in the use of rosiglitazone. N Engl J Med 2010 Nov 25;363(22):2081-4.
19. Shah BR, Juurlink DN, Austin PC, Mamdani MM. New use of rosiglitazone decreased following publication of a meta-analysis suggesting harm. Diabet Med 2008 Jul;25(7):871-4.
20. Levy AR, O’Brien BJ, Sellors C, Grootendorst P, Willison D. Coding accuracy of administrative drug claims in the Ontario Drug Benefit database. Can J Clin Pharmacol
2003;10:67-71.
21. Statistics Canada. Percentage of the Population aged 65 years and over – Ontario Censuses, 2009. Available from:http://www12.statcan.gc.ca/censusrecensement/2006/dp-pd/92-596/figure1.cfm?STID=203&Lang=eng&T=PR&PRCODE=35&GEOCODE=35&GEOLVL=PR&TID=0. Accessed on September 2011.
22. Pindyck RS, Rubinfeld DL. Econometric models and economic forecasts. Boston: Irwin/McGrawHill, 1998.
23. Huskamp HA, Deverka PA, Epstein AM, Epstein RS, McGuigan KA, Frank RG. The effect of incentive-based formularies on prescription-drug utilization and spending. NEngl J Med 2003;349:2224-2232.
24. Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the randomized aldactone evaluation study. N Engl J Med 2004;351(6):543-51.
25. Majumdar SR, McAlister FA, Soumerai SB. Synergy between publication and promotion: comparing adoption of new evidence in Canada and the United States. Am J Med 2003;115:467-72.
26. Beatriz CC, Rubinstein A. Influence of new evidence on prescription patterns. J Am Board Fam Pract 2002;15:457-62.