A systematic review of economic evaluations of pharmacological treatments for active tuberculosis.

Objectives: The continuing spread of tuberculosis (TB) worldwide, especially drug-resistant TB, poses a major challenge to healthcare systems globally. Addressing this requires appraising the cost effectiveness of existing pharmacological interventions against TB to identify key drivers of cost effectiveness and value and guide pharmaceutical innovation and novel drug regimen development. Methods: Studies were identified from a search of six database: MEDLINE MEDLINE-In Process, MEDLINE Epub Ahead of Print, EMBASE, Cochrane Database of Systematic Reviews, and Econlit in July 2022. Two reviewers independently assessed all identified studies and reports using pre-defined inclusion/exclusion criteria. Study methodological quality was assessed, data were extracted in standard tables, and results were narratively synthesized. Results: Overall, 991 studies and 53 HTA reports were identified with 20 studies and 3 HTA reports meeting the inclusion criteria. Quality assessment of the 20 studies identified 4 with minor limitations, while the remainder were assessed as having potentially or very serious limitations. Sixteen studies conducted cost-utility analyses, 6 conducted cost-effectiveness analyses, and 2 conducted cost-comparison analyses with some studies performing multiple analyses. The majority (n = 16) were model-based. Eleven studies analyzed the cost-effectiveness of bedaquiline, 6 compared shorter to longer/standard duration regimens, 2 assessed ethambutol, and 1 assessed delamanid. Key drivers of cost effectiveness were drug costs, the number of TB cases, the portion of cases with sputum culture conversion, treatment delivery costs, and treatment efficacy. Common value elements considered included adverse events, drug resistance, and improving treatment adherence. Conclusion: Our results suggest that out of the pharmacological treatments assessed, bedaquiline is likely a cost-effective addition to existing treatment regimens/background treatment regimens, while ethambutol is not likely to be. Newer shorter regimens, even if more costly, seem to be more cost-effective compared to longer regimens. These results illustrate the limited number of novel cost-effective pharmacological interventions and highlight a need to develop new drugs/regimens against TB to overcome resistance, taking into account the key drivers of cost effectiveness and other value attributes identified from this review.

Five-Year Sales for Newly Marketed Prescription Drugs With and Without Initial Orphan Drug Act Designation.

This study evaluates sales revenue earned in the first 5 years for newly marketed brand-name drugs with and without an initial orphan drug designation.

US public investment in development of mRNA covid-19 vaccines: retrospective cohort study.

OBJECTIVE: To estimate US public investment in the development of mRNA covid-19 vaccines. DESIGN: Retrospective cohort study. SETTING: Publicly funded science from January 1985 to March 2022. DATA SOURCES: National Institutes of Health (NIH) Report Portfolio Online Reporting Tool Expenditures and Results (RePORTER) and other public databases. Government funded grants were scored as directly, indirectly, or not likely related to four key innovations underlying mRNA covid-19 vaccines-lipid nanoparticle, mRNA synthesis or modification, prefusion spike protein structure, and mRNA vaccine biotechnology-on the basis of principal investigator, project title, and abstract. MAIN OUTCOME MEASURE: Direct public investment in research and vaccine development, stratified by the rationale, government funding agency, and pre-pandemic (1985-2019) versus pandemic (1 January 2020 to 31 March 2022). RESULTS: 34 NIH funded research grants that were directly related to mRNA covid-19 vaccines were identified. These grants combined with other identified US government grants and contracts totaled $31.9bn (£26.3bn; €29.7bn), of which $337m was invested pre-pandemic. Pre-pandemic, the NIH invested $116m (35%) in basic and translational science related to mRNA vaccine technology, and the Biomedical Advanced Research and Development Authority (BARDA) ($148m; 44%) and the Department of Defense ($72m; 21%) invested in vaccine development. After the pandemic started, $29.2bn (92%) of US public funds purchased vaccines, $2.2bn (7%) supported clinical trials, and $108m (<1%) supported manufacturing plus basic and translational science. CONCLUSIONS: The US government invested at least $31.9bn to develop, produce, and purchase mRNA covid-19 vaccines, including sizeable investments in the three decades before the pandemic through March 2022. These public investments translated into millions of lives saved and were crucial in developing the mRNA vaccine technology that also has the potential to tackle future pandemics and to treat diseases beyond covid-19. To maximize overall health impact, policy makers should ensure equitable global access to publicly funded health technologies.

Broad Patent Claims Come Before the Supreme Court in Amgen v Sanofi.

This Viewpoint discusses a current Supreme Court lawsuit, Amgen v Sanofi, involving Amgen's broad patents on PCSK9 that could effectively prevent other manufacturers from producing similar or even clinically superior antibodies, with important negative consequences for patients.

Recent Patent Reform Bills and Their Implications for Prescription Drugs.

This Viewpoint discusses 3 bills introduced recently in Congress that focus on patent eligibility, fraud, and quality and that have major implications for clinical medicine and pharmaceutical development.

Simulated Medicare Drug Price Negotiation Under the Inflation Reduction Act of 2022.

Importance: The Inflation Reduction Act of 2022 gives Medicare the authority to negotiate prices for certain prescription drugs. Which drugs will be selected and how prices will be negotiated remain unclear. Objective: To simulate drug selection and the minimum savings that would have been achieved at statutory ceiling prices if Medicare drug price negotiation had been implemented from 2018 to 2020. Design, Setting, and Participants: In this cross-sectional study, a policy simulation analysis of high-spending prescription drugs in Medicare Part B and Part D that were eligible for negotiation from January 2018 to December 2020 was performed from August 5 to November 20, 2022. Exposures: Eligibility criteria for selection and discounts afforded by the statutory ceiling prices for negotiation. Main Outcomes and Measures: The main outcomes were characteristics of drugs subject to negotiation and estimated Medicare savings from 2018 to 2020 that would have been achieved through spending at ceiling prices compared with existing net prices accounting for price concessions. Results: Among the 40 selected drugs, 35 were primarily reimbursed through Medicare Part D and 5 through Part B and 10 were biologics. The most common therapeutic classes were endocrine (11), neurologic or psychiatric (5), pulmonary (4), rheumatologic or immunologic (4), and cardiovascular (4). Median time from US Food and Drug Administration approval to selection was 12 years (IQR, 10-14 years). Three drugs faced generic competition in the 2 years between selection and price negotiation. For the remaining 37 drugs, estimated net Medicare spending from 2018 to 2020 was $55.3 billion; spending at ceiling prices would have been reduced by an estimated $26.5 billion, which represented 5% of estimated net Medicare drug spending during those 3 years. Conclusions and Relevance: In this cross-sectional study, simulating the drug price negotiation provisions in the Inflation Reduction Act of 2022 revealed important limitations, including strict selection criteria and the potential for drugs to become ineligible for negotiation during the 2 years between selection and prices taking effect. Despite these limitations, the policy still delivered substantial savings because ceiling prices offered steep discounts, in part, by erasing excess spending from price increases faster than inflation.

What Should US Policymakers Learn From International Drug Pricing Transparency Strategies?

This article analyzes differences in prescription drug pricing transparency practices among 3 Organisation for Economic Co-operation and Development member nations: the United Kingdom, Germany, and Canada. Specifically, this article compares these countries' policies on list and net price disclosures and on how international reference pricing is used to evaluate merits and drawbacks of different pricing transparency approaches. Finally, the article summarizes what policymakers in the United States should learn from these comparisons.

A Patient in His 50s With Chest Tightness and Left Arm and Neck Tingling.

This case report describes a diagnosis of aortic dissection after a patient presentation of chest tightness, light-headedness, and a tingling sensation in the left arm and neck.

Characteristics of Clinical Trials Evaluating Biosimilars in the Treatment of Cancer: A Systematic Review and Meta-analysis.

IMPORTANCE: Biologics account for almost half of US drug spending but may be subject to competitive pricing pressures by US Food and Drug Administration-approved biosimilars. The extent of the preapproval clinical testing that is needed and how these biosimilars compare with the originator biologic products remain critical issues in establishing a vibrant biosimilar market. OBJECTIVES: To analyze the design of cancer biosimilar efficacy studies compared with the reference drug pivotal trials and provide summary risk ratio estimates for each cancer type drug subgroup. DATA SOURCES: A systematic search was performed of articles and abstracts published using Embase, PubMed/MEDLINE, and ClinicalTrials.gov, last updated April 18, 2021. STUDY SELECTION: All studies or abstracts in English comparing a disease-modifying cancer biologic and its biosimilar and reporting efficacy or surrogate efficacy results were included. DATA EXTRACTION AND SYNTHESIS: Outcome estimates and study characteristics were extracted from each study. Among biosimilar efficacy studies, random-effects meta-analyses were performed for each cancer type molecule outcome subgroup, calculating pooled relative estimates and 95% CIs. MAIN OUTCOMES AND MEASURES: Study characteristics, such as population size, blinding, and randomization, were compared between biosimilar trials and those of reference drugs. Risk ratio estimates for relative change to surrogate measures (eg, progression-free survival) were collected for biosimilars and their reference products. RESULTS: A total of 31 cancer biosimilar studies of 3 reference products involving 12 310 patients were included. In all 7 subgroups, the biosimilars analyzed were indistinguishable from their reference drug on surrogate efficacy. Six reference drug trials were included, involving 1811 patients. On average, biosimilar studies involved more patients than reference drug trials (mean number of patients, 397 vs 302), were more likely to be randomized clinical trials rather than single-group or observational studies (100% [31 of 31] vs 50% [3 of 6]), and were more likely to be double blind rather than open label (84% [26 of 31] vs 17% [1 of 6]). CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found that the biosimilars for the cancer drugs in this sample were subjected to rigorous clinical evaluations, and the results were statistically indistinguishable from those of original products across drugs, cancer types, and outcome measures.

A Shot of Faith-Analyzing Vaccine Hesitancy in Certain Religious Communities in the United States.

Vaccine hesitancy in the United States continues to hamper ongoing coronavirus vaccination efforts. One set of populations with higher-than-average initial rates of vaccine hesitancy are certain religious groups, such as white evangelicals, African-American Protestants, and Hispanic Catholics. This article discusses the reasons underlying vaccine hesitancy in these populations, focusing on new trends in religious, political, and ideological beliefs that may influence vaccine acceptance. By using recent data and empirical case studies, this article describes how these trends could hinder the effectiveness of certain vaccine promotion strategies while also improving the potential efficacy of other forms of vaccine promotion, such as faith-based outreach. (100).

Promoting Competition in Drug Pricing: A Review of Recent Congressional Legislation.

Brand-name prescription drug manufacturers use various strategies to extend their market exclusivity periods by delaying generic or biosimilar competition. Recent Congressional legislation has targeted four such tactics. We analyze these proposals and assess their likely effect on competition in the U.S. drug market.