Availability and Cost of Expensive and Common Generic Prescription Drugs: A Cross-sectional Analysis of Direct-to-Consumer Pharmacies.

BACKGROUND: Direct-to-consumer (DTC) pharmacies sell generic prescription drugs, often at lower prices than traditional retail pharmacies; however, not all drugs are available, and prices vary. OBJECTIVE: To determine the availability and cost of generic drugs at DTC pharmacies. DESIGN: Cross-sectional study. SETTING: Five national DTC pharmacies in April and May 2023. PARTICIPANTS: Each qualifying form of 100 generic drugs with the highest cost-per-patient (expensive) and the 50 generic drugs with the highest number of patients (common) in Medicare Part D in 2020 MAIN MEASURES: Availability of these drugs and the lowest DTC pharmacy price for a standardized drug strength and supply (e.g., 30 pills), compared to GoodRx retail pharmacy prices. KEY RESULTS: Of the 118 expensive generic dosage forms, 94 (80%) were available at 1 or more DTC pharmacies; out of 52 common generic dosage forms, 51 (98%) were available (p < 0.001). Of the 88 expensive generics available in comparable quantities and strengths across pharmacies, 42 (47%) had the lowest cost at Amazon, 23 (26%) at Mark Cuban Cost Plus Drug Company, 13 (14%) at Health Warehouse, and 12 (13%) at Costco; for 51 common generic formulations, 16 (31%) had the lowest cost at Costco, 14 (27%) at Amazon, 10 (20%) at Walmart, 6 (12%) at Health Warehouse, and 5 (10%) at Mark Cuban Cost Plus Drug Company. For the 77 expensive generics with available GoodRx retail pharmacy prices, the median cost savings at DTC pharmacies were $231 (95% CI, $129-$792) or 76% (IQR, 53-91%); for 51 common generics, savings were $19 (95% CI, $10-$34) or 75% (IQR, 67-83%). CONCLUSIONS: Many of the most expensive generic drugs are unavailable at direct-to-consumer pharmacies. Meanwhile, less expensive, commonly used generics are widely available, but drug prices vary by pharmacy and savings are modest, requiring patients to shop around for the lowest cost.

High Cost of Chimeric Antigen Receptor T-Cells: Challenges and Solutions.

Chimeric antigen receptor (CAR) T-cells are a cellular immunotherapy with remarkable efficacy in treating multiple hematologic malignancies but they are associated with extremely high prices that are, for many countries, prohibitively expensive. As their use increases both for hematologic malignancies and other indications, and large numbers of new cellular therapies are developed, novel approaches will be needed both to reduce the cost of therapy, and to pay for them. We review the many factors that lead to the high cost of CAR T-cells and offer proposals for reform.

Federal Funding For Discovery And Development Of Costly HIV Drugs Was Far More Than Previously Estimated.

In July 2012, tenofovir disoproxil fumarate-emtricitabine (TDF-FTC, brand name Truvada) was approved by the Food and Drug Administration (FDA) to prevent HIV infection. To estimate the extent of the US government's direct financial contribution to the discovery and development of Truvada, we identified National Institutes of Health awards using FDA documents, peer-reviewed literature, patent records, court filings, and other publicly available materials. We classified seventy-three federal government awards to eleven researchers as being directly linked to the development and clinical testing of Truvada for prevention therapy, through which the US government spent an estimated $143 million. The substantial public funding raises questions about the high price charged by the drug's manufacturer, which reduced its affordability and limited its accessibility as HIV preventive therapy.

High-Priced Sickle Cell Gene Therapies Threaten to Exacerbate US Health Disparities and Establish New Pricing Precedents for Molecular Medicine.

Gene therapies to treat sickle cell disease are in development and are expected to have high costs. The large eligible population size - by far, the largest for a gene therapy - poses daunting budget challenges and threatens to exacerbate health disparities for Black patients, who make up the vast majority of American sickle cell patients.

Diabetes Drugs: List Price Increases Were Not Always Reflected In Net Price; Impact Of Brand Competition Unclear.

List prices for brand-name drugs have risen steeply, often despite the introduction of competition from other brand-name drugs in the same therapeutic class. List prices, however, do not reflect any rebates that manufacturers provide payers. To understand how net prices (after rebates and other discounts) respond to competition, we compared changes in inflation-adjusted, revenue-weighted mean list and net prices of a one-month supply of three classes of diabetes drugs: glucagon-like peptide 1 (GLP1) agonists, dipeptidyl peptidase 4 (DPP4) inhibitors, and sodium glucose cotransporter 2 (SGLT2) inhibitors. These drug classes each had several brand-name products enter the market between 2005 and 2017. The annualized change in list price over this period was $75 (15 percent) for GLP1 agonists, $22 (8 percent) for DPP4 inhibitors, and $41 (11 percent) for SGLT2 inhibitors. In contrast, the annualized change in net price was $38 (10 percent) for GLP1 agonists, -$3 (-2 percent) for DPP4 inhibitors, and -$17 (-9 percent) for SGLT2 inhibitors, suggesting a variable impact of brand-name competition on net prices.

Public funding for transformative drugs: the case of sofosbuvir.

The approval of sofosbuvir (Sovaldi) in 2013 transformed chronic hepatitis C virus (HCV) care, but its high cost was criticized in part because of reports of substantial public involvement in its development. We developed a methodology to assess the public's contribution through the National Institutes of Health (NIH) in developing sofosbuvir. Using key terms from the timeline of sofosbuvir, we identified articles in PubMed; linked them to federal funding using the NIH RePORTER; reviewed the title, organization, and investigator of each resulting award for relatedness; and converted related awards to 2018 US dollars. Of 6043 unique awards, we identified 29 that were directly (US$7.7 million) and 110 that were indirectly (US$53.2 million) related awards made to major academic institutions and companies engaged in the development of the drug. These findings indicate that public funding had a key role in developing sofosbuvir, with an estimated US$60.9 million provided in NIH funding.

US Spending Associated With Transition From Daily to 3-Times-Weekly Glatiramer Acetate.

Importance: Market exclusivity for daily injections of glatiramer acetate, a disease-modifying therapy for multiple sclerosis, expired in 2015. In 2014, the manufacturer launched an alternate 3-times-weekly version that was widely adopted, sustaining market dominance of brand-name glatiramer until late 2017. Objective: To estimate excess US spending associated with the transition from daily to 3-times-weekly glatiramer. Design, Setting, and Participants: This economic evaluation estimated total US glatiramer spending from January 1, 2011, to June 30, 2019, using a national cohort from 3 data sources that collectively represent approximately 40% of the US glatiramer market: Medicare Part D, Medicaid, and a claims database of commercially insured and Medicare Advantage patients. Exposures: Calendar quarter. Main Outcomes and Measures: Outcomes were quarterly US glatiramer spending, estimated as price × use. Manufacturer list prices for generic products and estimates of net (postrebate) prices for brand-name products were used. Linear regression and interrupted time series models were used to compare spending trends in 3 periods: before generic competition (2011-2015), during generic competition for daily glatiramer (2015-2017), and during generic competition for daily and 3-times-weekly glatiramer (2017-2019). Results: From 2011 to 2015, US glatiramer spending increased to $962 million per quarter and did not decrease with generic competition of only daily glatiramer (2015-2017). After generic competition began for 3-times-weekly glatiramer in 2017, prices decreased by 47% to 64%, and spending decreased to $508 million per quarter in 2019 (P < .001 for slope). The delay in decreased spending from 2015 to 2017 was associated with excess spending of $4.3 billion to $6.5 billion. Conclusions and Relevance: These findings suggest that 2.5 years of delayed generic competition related to introduction of a new version of branded glatiramer acetate was associated with $4.3 billion to $6.5 billion in excess spending. Extended market exclusivity from introducing a new version of an existing brand-name drug can yield manufacturer returns out of proportion to the level of investment or risk involved; more limited incentives could encourage incremental innovations to existing drugs at a lower societal cost.

Randomized Study of Providing Evidence Context to Mitigate Physician Misinterpretation Arising From Off-Label Drug Promotion.

BACKGROUND: Recent court decisions have thrown into question the Food and Drug Administration's rules limiting manufacturer promotion of prescription drugs for unapproved uses. We assessed how providing pro forma disclosures or more descriptive evidence context about the data supporting an off-label claim affected physicians' beliefs about drug efficacy. METHODS AND RESULTS: In online and mailed surveys, we randomized national samples of board-certified, clinically active cardiologists, internists, and endocrinologists to receive 1 of 3 information scenarios about a hypothetical drug derived verbatim from excerpts on the website for Vascepa, a prescription fish oil for which Food and Drug Administration specially permitted off-label promotion after a manufacturer lawsuit. The scenarios presented information about the approved on-label indication (severe hypertriglyceridemia), off-label claim + pro forma disclaimers (suggestive but not conclusive evidence for use as an add-on to a statin for patients reaching low-density lipoprotein goal but with persistent moderate hypertriglyceridemia), and off-label claim + evidence context (eg, reports on 3 trials failing to demonstrate cardiovascular benefit of other triglyceride-lowering drugs for such patients). Among 686 respondents (48% response rate), 29% reported receiving off-label information about Vascepa (ie, use as an add-on to a statin) from the manufacturer, and 16% had prescribed it off-label for this purpose. Off-label prescribing was 5 times higher among physicians who received such off-label information (38% versus 7%, P<0.001). For the hypothetical drug, the proportion of physicians endorsing the unproven claim that the drug reduced cardiovascular risk was similar among those randomized to the on-label and off-label claim + pro forma disclaimers scenarios (35% versus 37% [95% CI, -6% to 11%]), but substantially lower among those randomized to the off-label claim + evidence context scenario (21% [95% CI, -24% to 7%]). CONCLUSIONS: Physicians who received company information about the unapproved use of Vascepa were more likely to report prescribing it off-label. Supplementing off-label claims with evidence context improved the prescribers' knowledge and reduced enthusiasm for the unproven, off-label indication of reducing cardiovascular risk.

Physician Perceptions of Step Therapy Prescribing Requirements.

BACKGROUND: Step therapy policies that require prescribers to follow an ordered protocol for drug choices are widely used by public and private insurers to manage medication costs; however, the perceptions of prescribing physicians regarding these policies have not been studied. OBJECTIVE: To determine physician attitudes toward step therapy policies and the correlation of these beliefs with physician characteristics. METHODS: A sample of clinically active physicians specializing in internal medicine, cardiology, or endocrinology received a survey administered online or via mail. Five-point Likert scale questions assessed physicians' opinions of clinical, economic, and implementation elements of prior authorization policies; physician demographic characteristics; and the extent of their interactions with the pharmaceutical industry. RESULTS: 686 physicians (48%) responded to the survey, which was evenly divided among primary care physicians, endocrinologists, and cardiologists. Many respondents (70%) had interactions with industry, including receipt of meals or gifts and use of medication samples. Physicians reported that step therapy policies could improve the affordability of medication use (55% agree vs. 26% disagree) and its clinical appropriateness (59% agree vs. 19% disagree). By similar margins, however, physicians stated that step therapy policies were implemented inefficiently and inflexibly and often did not incorporate relevant patient-specific information. Physicians in subspecialties, especially endocrinology, and those who had interactions with the pharmaceutical industry were more likely to hold negative views of step therapy policies. CONCLUSIONS: Most physicians recognize the potential of step therapy to improve the quality and cost-effectiveness of prescribing, although interactions with industry may affect these opinions. Physician perception of ineffective implementation of these policies, however, undermines their acceptability. DISCLOSURES: The American Board of Internal Medicine (ABIM) funded the survey used in this study. The ABIM had no role in the design and conduct of the study or development and preparation of the manuscript. Survey honoraria was provided by the Consumers Union. Kesselheim and Avorn's work is funded by the Laura and John Arnold Foundation. Kesselheim is also supported by the Harvard-MIT Center for Regulatory Science, Arnold Ventures, and the Engelberg Foundation. Ross is employed by the ABIM. Fischer, Lu, and Tessema have nothing to disclose.

Assessing the Justification, Funding, Success, and Survival Outcomes of Randomized Noninferiority Trials of Cancer Drugs: A Systematic Review and Pooled Analysis.

Importance: Noninferiority trials test whether a new intervention is not worse than the comparator by a given margin. Objectives: To study the characteristics of published randomized noninferiority trials in oncology with overall survival as an end point, to assess the association of justification and success in achieving noninferiority with the funding of these trials, and to evaluate the association of such trials with patient survival. Data Sources: A systematic search of PubMed and Google Scholar databases was conducted in March 2018, with no date restrictions. Study Selection: Randomized noninferiority trials of cancer drug therapies with overall survival as an end point were included. Trials of decision support, supportive care, and nondrug treatment in both arms were excluded. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for meta-epidemiological studies. Studies were screened for eligibility criteria, and data on criteria for noninferiority, funding, success (achieving noninferiority), and hazard ratios with confidence intervals for overall survival were extracted. Hazard ratios for overall survival were pooled across trials using a random-effects model. Main Outcomes and Measures: Associations of the justification for using a noninferiority design and success in achieving noninferiority with the source of funding were assessed. Overall pooled hazard ratios and confidence intervals for overall survival were calculated. Results: Among 74 noninferiority trials of cancer drug therapies, 23 (31%; enrolling 21 437 patients) used overall survival as the primary end point. The noninferiority margins for the hazard ratio of overall survival ranged from 1.08 to 1.33. Noninferiority design was justified in 14 trials (61%) but not in 9 (39%). Overall, 18 trials (78%) concluded with a finding of noninferiority. Industry funding was associated with lack of justification for noninferiority design (P = .02, assessed using the Fisher exact test) but not with success in proving noninferiority (P = .80, assessed using the Fisher exact test). When the hazard ratios across the trials were pooled, there was no beneficial or detrimental association with overall survival, with a pooled hazard ratio of 0.97 (95% CI, 0.92-1.02). Conclusions and Relevance: The findings suggest that a substantial fraction of noninferiority trials in oncology, most of which are industry funded, lack justification for such a design. Greater attention to the use of noninferiority designs in randomized clinical trials of cancer drugs from local and national regulators is warranted.