Publications

2014

Gellad, Walid F, Phillip Choi, Margaret Mizah, Chester B Good, and Aaron S Kesselheim. (2014) 2014. “Assessing the Chiral Switch: Approval and Use of Single-Enantiomer Drugs, 2001 to 2011.”. The American Journal of Managed Care 20 (3): e90-7.

OBJECTIVES: A "chiral switch" occurs in the pharmaceutical market when a drug made up of 2 enantiomer forms is replaced with a purified single-enantiomer version, often in the context of a patent expiration. We studied the prevalence of chiral switching in the United States over the past decade, including trends in use of, and expenditures on, these products in Medicaid.

STUDY DESIGN: Retrospective analysis.

METHODS: We used US Adopted Names prefixes (lev/levo/ar/es/dex/dextro) to identify all single-enantiomer drugs approved from 2001 to 2011. From publicly available US Food and Drug Administration (FDA) approval documents, we extracted the characteristics of the pivotal premarket trials for the single enantiomers. Specifically, we evaluated whether the single enantiomer was directly compared with the precursor racemic drug and whether there was evidence of superior efficacy. We used quarterly drug expenditure data from each state Medicaid program to chart trends in use of, and spending on, the single-enantiomer products and their racemic precursors during the study period.

RESULTS: From 2001 to 2011, the FDA approved 9 single-enantiomer products: dexlansoprazole, levoleucovorin, levocetirizine, armodafinil, arformoterol, eszopiclone, escitalopram, dexmethylphenidate, and esomeprazole. Of those 9 drugs, 3 had at least 1 pre-approval randomized trial that included the racemic precursor as a direct comparator, but there was no evidence of superiority of the single enantiomer over the racemic at comparable doses. Between 2001 and 2011, US Medicaid programs spent approximately $6.3 billion on these 9 single-enantiomer drugs.

CONCLUSIONS: Recently approved single-enantiomer drugs showed no evidence of superior efficacy over the older racemic precursors in the pivotal trials leading to their approval, and in a majority of cases, they were not directly compared.

Vater, Laura B, Julie M Donohue, Robert Arnold, Douglas B White, Edward Chu, and Yael Schenker. (2014) 2014. “What Are Cancer Centers Advertising to the Public?: A Content Analysis.”. Annals of Internal Medicine 160 (12): 813-20. https://doi.org/10.7326/M14-0500.

BACKGROUND: Although critics have expressed concerns about cancer center advertising, analyses of the content of these advertisements are lacking.

OBJECTIVE: To characterize the informational and emotional content of direct-to-consumer cancer center advertisements.

DESIGN: Content analysis.

SETTING: Top U.S. consumer magazines (n = 269) and television networks (n = 44) in 2012.

MEASUREMENTS: Types of clinical services promoted; information provided about clinical services, including risks, benefits, costs, and insurance availability; use of emotional advertising appeals; and use of patient testimonials were assessed. Two investigators independently coded advertisements using ATLAS.ti, and κ values ranged from 0.77 to 1.00.

RESULTS: A total of 102 cancer centers placed 409 unique clinical advertisements in top media markets in 2012. Advertisements promoted treatments (88%) more often than screening (18%) or supportive services (13%). Benefits of advertised therapies were described more often than risks (27% vs. 2%) but were rarely quantified (2%). Few advertisements mentioned coverage or costs (5%), and none mentioned specific insurance plans. Emotional appeals were frequent (85%), evoking hope for survival (61%), describing cancer treatment as a fight or battle (41%), and inducing fear (30%). Nearly one half of advertisements included patient testimonials, which were usually focused on survival, rarely included disclaimers (15%), and never described the results that a typical patient may expect.

LIMITATION: Internet advertisements were not included.

CONCLUSION: Clinical advertisements by cancer centers frequently promote cancer therapy with emotional appeals that evoke hope and fear while rarely providing information about risks, benefits, costs, or insurance availability. Further work is needed to understand how these advertisements influence patient understanding and expectations of benefit from cancer treatments.

PRIMARY FUNDING SOURCE: National Institutes of Health.

Tang, Yan, Walid F Gellad, Aiju Men, and Julie M Donohue. (2014) 2014. “Impact of Medicare Part D Plan Features on Use of Generic Drugs.”. Medical Care 52 (6): 541-8. https://doi.org/10.1097/MLR.0000000000000142.

BACKGROUND: Little is known about how Medicare Part D plan features influence choice of generic versus brand drugs.

OBJECTIVES: To examine the association between Part D plan features and generic medication use.

METHODS: Data from a 2009 random sample of 1.6 million fee-for-service, Part D enrollees aged 65 years and above, who were not dually eligible or receiving low-income subsidies, were used to examine the association between plan features (generic cost-sharing, difference in brand and generic copay, prior authorization, step therapy) and choice of generic antidepressants, antidiabetics, and statins. Logistic regression models accounting for plan-level clustering were adjusted for sociodemographic and health status.

RESULTS: Generic cost-sharing ranged from $0 to $9 for antidepressants and statins, and from $0 to $8 for antidiabetics (across 5th-95th percentiles). Brand-generic cost-sharing differences were smallest for statins (5th-95th percentiles: $16-$37) and largest for antidepressants ($16-$64) across plans. Beneficiaries with higher generic cost-sharing had lower generic use [adjusted odds ratio (OR)=0.97, 95% confidence interval (CI), 0.95-0.98 for antidepressants; OR=0.97, 95% CI, 0.96-0.98 for antidiabetics; OR=0.94, 95% CI, 0.92-0.95 for statins]. Larger brand-generic cost-sharing differences and prior authorization were significantly associated with greater generic use in all categories. Plans could increase generic use by 5-12 percentage points by reducing generic cost-sharing from the 75th ($7) to 25th percentiles ($4-$5), increasing brand-generic cost-sharing differences from the 25th ($25-$26) to 75th ($32-$33) percentiles, and using prior authorization and step therapy.

CONCLUSIONS: Cost-sharing features and utilization management tools were significantly associated with generic use in 3 commonly used medication categories.

Marcum, Zachary A, Julia Driessen, Carolyn T Thorpe, Walid F Gellad, and Julie M Donohue. (2014) 2014. “Effect of Multiple Pharmacy Use on Medication Adherence and Drug-Drug Interactions in Older Adults With Medicare Part D.”. Journal of the American Geriatrics Society 62 (2): 244-52. https://doi.org/10.1111/jgs.12645.

OBJECTIVES: To assess the association between multiple pharmacy use and medication adherence and potential drug-drug interactions (DDIs) in older adults.

DESIGN: Cross-sectional propensity score-weighted analysis.

SETTING: 2009 claims data.

PARTICIPANTS: A nationally representative sample of 926,956 Medicare Part D beneficiaries aged 65 and older continuously enrolled in fee-for-service Medicare and Part D that year who filled one or more prescriptions at a community retail or mail order pharmacy.

MEASUREMENTS: Multiple pharmacy use was defined as concurrent (overlapping time periods) or sequential use (non-overlapping time periods) of ≥ 2 pharmacies in the year. Medication adherence was calculated using a proportion of days covered of 0.80 or greater for eight therapeutic categories (beta-blockers, renin angiotensin system antagonists, calcium channel blockers, statins, sulfonylureas, biguanides (metformin), thiazolidinediones, and dipeptidyl peptidase-IV inhibitors). Potential DDIs arising from use of certain drugs across a broad set of classes were defined as the concurrent filling of two interacting drugs.

RESULTS: Overall, 38.1% of the sample used multiple pharmacies. Those using multiple pharmacies (concurrently or sequentially) consistently had higher adjusted odds of nonadherence (ranging from 1.10 to 1.31, P < .001) across all chronic medication classes assessed after controlling for sociodemographic, health status, and access to care factors than single pharmacy users. The adjusted predicted probability of exposure to a DDI was also slightly higher for those using multiple pharmacies concurrently (3.6%) than for single pharmacy users (3.2%, adjusted odds ratio (AOR) = 1.11, 95% confidence interval (CI) = 1.08-1.15) but lower in individuals using multiple pharmacies sequentially (2.8%, AOR = 0.85, 95% CI = 0.81-0.91).

CONCLUSIONS: Filling prescriptions at multiple pharmacies was associated with lower medication adherence across multiple chronic medications and a small but statistically significant greater likelihood of DDIs in concurrent pharmacy users.

Gallini, Adeline, Sandrine Andrieu, Julie M Donohue, Naïma Oumouhou, Maryse Lapeyre-Mestre, and Virginie Gardette. (2014) 2014. “Trends in Use of Antipsychotics in Elderly Patients With Dementia: Impact of National Safety Warnings.”. European Neuropsychopharmacology : The Journal of the European College of Neuropsychopharmacology 24 (1): 95-104. https://doi.org/10.1016/j.euroneuro.2013.09.003.

Based on evidence of an increased risk of death, drug agencies issued safety warnings about the use of second generation antipsychotics (SGAs) in the elderly with dementia. The French agency issued a warning in 2004. which was extended to all antipsychotics in 2008. Little is known about the impact of these warnings on use. We conducted a quasi-experimental study (interrupted time-series) in France, for 2003-2011, including subjects aged ≥65 with dementia and subjects aged ≥65 without dementia in the EGB database (1/97th representative random sample of claims from the main Health Insurance scheme). Outcomes were monthly rates of use of antipsychotics (by class and agent) and of five comparison drug classes (antidepressants, benzodiazepines, dermatologicals, antidiabetics, antiasthmatics). Trends were analyzed by joinpoint regression, impact of warnings by linear segmented regression. In patients with dementia (n=7169), there was a 40% reduction in antipsychotic use from 14.2% in 2003 to 10.2% in 2011. The reduction began before 2004 and was unaffected by the warnings. Use of first generation antipsychotics declined over the period, while use of SGAs increased and leveled off from 2007. Use of the five comparison drug classes increased on the period. In subjects without dementia (n=91,942), rates of overall antipsychotic use decreased from 2.3% in 2003 to 1.8% in 2011 with no effect of the warnings. Meanwhile, use of SGAs continuously increased from 0.37% to 0.64%. Antipsychotic use decreased in the elderly between 2003 and 2011, especially in dementia. The timing of the decrease, however, did not coincide with safety warnings.

Donohue, Julie M, Bea Herbeck Belnap, Aiju Men, Fanyin He, Mark S Roberts, Herbert C Schulberg, Charles F Reynolds, and Bruce L Rollman. (2014) 2014. “Twelve-Month Cost-Effectiveness of Telephone-Delivered Collaborative Care for Treating Depression Following CABG Surgery: A Randomized Controlled Trial.”. General Hospital Psychiatry 36 (5): 453-9. https://doi.org/10.1016/j.genhosppsych.2014.05.012.

OBJECTIVE: To determine the 12-month cost-effectiveness of a collaborative care (CC) program for treating depression following coronary artery bypass graft (CABG) surgery versus physicians' usual care (UC).

METHODS: We obtained 12 continuous months of Medicare and private medical insurance claims data on 189 patients who screened positive for depression following CABG surgery, met criteria for depression when reassessed by telephone 2 weeks following hospitalization (nine-item Patient Health Questionnaire ≥10) and were randomized to either an 8-month centralized, nurse-provided and telephone-delivered CC intervention for depression or to their physicians' UC.

RESULTS: At 12 months following randomization, CC patients had $2068 lower but statistically similar estimated median costs compared to UC (P=.30) and a variety of sensitivity analyses produced no significant changes. The incremental cost-effectiveness ratio of CC was -$9889 (-$11,940 to -$7838) per additional quality-adjusted life-year (QALY), and there was 90% probability it would be cost-effective at the willingness to pay threshold of $20,000 per additional QALY. A bootstrapped cost-effectiveness plane also demonstrated a 68% probability of CC "dominating" UC (more QALYs at lower cost).

CONCLUSIONS: Centralized, nurse-provided and telephone-delivered CC for post-CABG depression is a quality-improving and cost-effective treatment that meets generally accepted criteria for high-value care.