ABSTRACT
The cost of drug discovery and development is driven primarily by failure1, with only about 10% of clinical programmes eventually receiving approval2-4. We previously estimated that human genetic evidence doubles the success rate from clinical development to approval5. In this study we leverage the growth in genetic evidence over the past decade to better understand the characteristics that distinguish clinical success and failure. We estimate the probability of success for drug mechanisms with genetic support is 2.6 times greater than those without. This relative success varies among therapy areas and development phases, and improves with increasing confidence in the causal gene, but is largely unaffected by genetic effect size, minor allele frequency or year of discovery. These results indicate we are far from reaching peak genetic insights to aid the discovery of targets for more effective drugs.
Subject(s)
Clinical Trials as Topic , Drug Approval , Drug Discovery , Treatment Outcome , Humans , Alleles , Clinical Trials as Topic/economics , Clinical Trials as Topic/statistics & numerical data , Drug Approval/economics , Drug Discovery/economics , Drug Discovery/methods , Drug Discovery/statistics & numerical data , Drug Discovery/trends , Gene Frequency , Genetic Predisposition to Disease , Molecular Targeted Therapy , Probability , Time Factors , Treatment FailureABSTRACT
BACKGROUND: The potential role played by launch price and clinical value in reimbursement decisions has not been sufficiently established in China. This study aimed to investigate the association of launch price and clinical value with reimbursement decisions for anticancer drugs after the implementation of reimbursement-linked price negotiation in China. METHODS: Anticancer drugs approved by the National Medical Products Administration (NMPA) of China from January 2017 to June 2022 were eligible for inclusion. Approval and reimbursement dates of included drug indications were retrieved from publicly available resources. We collected measures of clinical value, including survival, quality of life (QoL), and overall response rate from pivotal clinical trials and calculated treatment price at launch. Univariate and multivariate Cox proportional hazards models were employed to estimate the association between launch price, clinical value, and reimbursement decisions of anticancer drugs in China. RESULTS: The median reimbursement lag was 579 days (interquartile range [IQR]: 402-936) for 93 indications supported by randomized controlled trials and 637 days (IQR: 373-858) for 42 indications supported by single-arm clinical trials. Reimbursement was granted to 60 (65%) and 23 (55%) indications supported by randomized controlled and single-arm clinical trials, respectively. The launch price of anticancer drugs was not associated with reimbursement decisions in multivariate regression analyses. Indications supported by randomized controlled trials with higher clinical value were more likely to be reimbursed (hazard ratio [HR] for survival=1.07, 95% CI: 1.00-1.15, P=.037), while the overall response rate of indications supported by single-arm clinical trials was not associated with the likelihood of being reimbursed (HR=2.09, 95% CI: 0.14-32.28, P=.595). CONCLUSION: The launch price of anticancer drugs may not have a significant impact on reimbursement decisions, while the implementation of reimbursement-linked price negotiation in China has prioritized anticancer drugs with higher clinical value, but only for indications supported by randomized controlled trials. Efforts are needed to prioritize indications supported by single-arm clinical trials that have higher value during the process of price negotiation.
Subject(s)
Antineoplastic Agents , Insurance, Health, Reimbursement , Reimbursement Mechanisms , China , Humans , Antineoplastic Agents/economics , Antineoplastic Agents/therapeutic use , Reimbursement Mechanisms/economics , Insurance, Health, Reimbursement/economics , Drug Costs/statistics & numerical data , Quality of Life , Drug Approval/economics , Proportional Hazards ModelsSubject(s)
Alzheimer Disease , Centers for Medicare and Medicaid Services, U.S. , Drug Approval , United States Food and Drug Administration , Humans , Alzheimer Disease/drug therapy , Alzheimer Disease/economics , Centers for Medicare and Medicaid Services, U.S./economics , Centers for Medicare and Medicaid Services, U.S./legislation & jurisprudence , Drug Approval/economics , Drug Approval/legislation & jurisprudence , United States , United States Food and Drug Administration/legislation & jurisprudenceABSTRACT
Importance: Increasingly, cost-effectiveness analyses are being done to determine the value of rapidly increasing oncology drugs; however, this assumes that these analyses are unbiased. Objective: To analyze the characteristics of cost-effectiveness studies and to determine characteristics associated with whether an oncology drug is found to be cost-effective. Design, Setting, and Participants: This retrospective cross-sectional study included 254 cost-effectiveness analyses for 116 oncology drugs that were approved by the US Food and Drug Administration from 2015 to 2020. Exposures: Each drug was analyzed for the incremental cost-effectiveness ratio per quality-adjusted life year, the funding of the study, the authors' conflict of interest, the threshold of willingness-to-pay, from what country's perspective the analysis was done, and whether a National Institute for Health and Care Excellence cost-effectiveness analysis had been done. Main Outcomes and Measures: The main outcome was the odds of a study concluding that a drug was cost-effective. Results: There were 116 drug approvals with 254 studies and country perspectives. Of the country perspectives, 132 (52%) were from the US. Forty-seven of 78 drugs with cost-effective studies had been shown to improve overall survival, whereas 15 of 38 of drugs without a cost-effectiveness study had been shown to improve overall survival. Having a study funded by a pharmaceutical company was associated with higher odds of a study concluding that a drug was cost-effective than studies without funding (odds ratio, 41.36; 95% CI, 11.86-262.23). Conclusions and Relevance: In this cross-sectional study, pharmaceutical funding was associated with greater odds that an oncology drug would be found to be cost-effective. These findings suggest that simply disclosing potential conflict of interest is inadequate. We encourage cost-effectiveness analyses by independent groups.
Subject(s)
Antineoplastic Agents/economics , Antineoplastic Agents/therapeutic use , Cost-Benefit Analysis/statistics & numerical data , Cost-Benefit Analysis/trends , Drug Approval/economics , Drug Approval/statistics & numerical data , Neoplasms/drug therapy , Cross-Sectional Studies , Forecasting , Humans , Retrospective Studies , United States , United States Food and Drug Administration/statistics & numerical dataSubject(s)
Antineoplastic Agents/economics , Drug Approval/economics , Neoplasms/drug therapy , Reimbursement Mechanisms , Antineoplastic Agents/therapeutic use , Centers for Medicare and Medicaid Services, U.S. , Clinical Trials as Topic , Drug Approval/methods , Drug Costs , Humans , Medicare Part B/economics , Models, Theoretical , Neoplasms/mortality , Standard of Care , Treatment Outcome , United States , United States Food and Drug AdministrationABSTRACT
Important breakthroughs in medical treatments have improved outcomes for patients suffering from several types of cancer. However, many oncological treatments approved by regulatory agencies are of low value and do not contribute significantly to cancer mortality reduction, but lead to unrealistic patient expectations and push even affluent societies to unsustainable health care costs. Several factors that contribute to approvals of low-value oncology treatments are addressed, including issues with clinical trials, bias in reporting, regulatory agency shortcomings and drug pricing. With the COVID-19 pandemic enforcing the elimination of low-value interventions in all fields of medicine, efforts should urgently be made by all involved in cancer care to select only high-value and sustainable interventions. Transformation of medical education, improvement in clinical trial design, quality, conduct and reporting, strict adherence to scientific norms by regulatory agencies and use of value-based scales can all contribute to raising the bar for oncology drug approvals and influence drug pricing and availability.
Subject(s)
Drug Approval , Drug Costs , Medical Oncology/ethics , Antineoplastic Agents/economics , Antineoplastic Agents/therapeutic use , Bias , COVID-19/epidemiology , Cost Control/ethics , Cost Control/organization & administration , Cost Control/standards , Cultural Evolution , Drug Approval/economics , Drug Approval/legislation & jurisprudence , Drug Approval/organization & administration , Drug Costs/ethics , Drug Costs/legislation & jurisprudence , Humans , Medical Oncology/economics , Medical Oncology/organization & administration , Medical Oncology/standards , Neoplasms/drug therapy , Neoplasms/economics , Neoplasms/mortality , Organizational Innovation , PandemicsSubject(s)
Biological Products , Drug Approval , Drug Development , Public Sector , Biological Products/economics , Biological Products/pharmacology , Drug Approval/economics , Drug Approval/methods , Drug Costs , Drug Development/economics , Drug Development/methods , Drug and Narcotic Control/economics , Humans , Orphan Drug Production/methods , Public Sector/economics , Public Sector/statistics & numerical data , United Kingdom , United StatesSubject(s)
Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/economics , Drug Approval/economics , Fees, Pharmaceutical , Homozygous Familial Hypercholesterolemia/drug therapy , Homozygous Familial Hypercholesterolemia/economics , Humans , Infusions, Intravenous , Orphan Drug Production/economicsSubject(s)
COVID-19 , Drug Approval/economics , Pandemics , Humans , United States , United States Food and Drug AdministrationABSTRACT
DISCLOSURES: No funding contributed to the writing of this commentary. Both authors are employed by the Cystic Fibrosis Foundation. The Cystic Fibrosis Foundation has entered into therapeutic development award agreements and licensing agreements to assist with the development of CFTR modulators that may result in intellectual property rights, royalties, and other forms of consideration provided to CFF. Some of these agreements are subject to confidentiality restrictions and, thus, CFF cannot comment on them.
Subject(s)
Chloride Channel Agonists/therapeutic use , Cystic Fibrosis Transmembrane Conductance Regulator/agonists , Cystic Fibrosis/drug therapy , Drug Costs , Aminophenols/economics , Aminophenols/therapeutic use , Benzodioxoles/economics , Benzodioxoles/therapeutic use , Chloride Channel Agonists/economics , Cystic Fibrosis/economics , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Drug Approval/economics , Drug Combinations , Humans , Indoles/economics , Indoles/therapeutic use , Medical Assistance , Mutation , Pyrazoles/economics , Pyrazoles/therapeutic use , Pyridines/economics , Pyridines/therapeutic use , Quinolines/economics , Quinolines/therapeutic use , Quinolones/economics , Quinolones/therapeutic use , Treatment Outcome , United States , United States Food and Drug AdministrationABSTRACT
DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Seidner, Rind, and Pearson are employed by ICER. Tice reports contracts to his institution, University of California, San Francisco, from ICER during the conduct of this study. Wherry has nothing to disclose.
Subject(s)
Chloride Channel Agonists/therapeutic use , Cost-Benefit Analysis , Cystic Fibrosis Transmembrane Conductance Regulator/agonists , Cystic Fibrosis/drug therapy , Models, Economic , Adolescent , Aminophenols/economics , Aminophenols/therapeutic use , Aminopyridines/economics , Aminopyridines/therapeutic use , Benzodioxoles/economics , Benzodioxoles/therapeutic use , Child , Chloride Channel Agonists/economics , Cystic Fibrosis/economics , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Drug Approval/economics , Drug Combinations , Drug Costs , Health Policy/economics , Humans , Indoles/economics , Indoles/therapeutic use , Mutation , Pyrazoles/economics , Pyrazoles/therapeutic use , Pyridines/economics , Pyridines/therapeutic use , Quinolines/economics , Quinolines/therapeutic use , Quinolones/economics , Quinolones/therapeutic use , Treatment Outcome , United States , United States Food and Drug AdministrationABSTRACT
Brand-name drugs have periods of market exclusivity before generic competition begins. Due to high brand-name drug prices charged during this period, market exclusivity is an important determinant of US prescription drug spending. We used claims data to estimate the market exclusivity period for 264 small molecule and 4 biologic drugs that faced new generic or biosimilar competition from 2012-2018. Exclusivity periods were longer for biologics compared with new small molecule drugs (median 21.5 vs. 14.4 years, P = 0.02), longer for drugs with annual revenue < $75 million compared with those with revenue ≥ $500 million (16.6 vs. 14.2 years, P = 0.01), and shorter in cases for which the first generic was granted 180 days of exclusivity, which is an incentive designed to expedite generic competition (14.1 vs. 15.9 years, P < 0.01). Modified versions of existing products had shorter exclusivities than new drugs (9.9 vs. 14.5 years, P < 0.01), with variation by route of administration, therapeutic area, and use of expedited approval pathways. Exclusivity periods for new drugs ranging from 13-17 years are similar to older estimates, but longer exclusivity among the small number of biologics in the cohort raises concern that overall median exclusivity may lengthen in the future because biologics represent a larger fraction of new drug approvals over the last decade than they did the previous decade. Unnecessarily long exclusivity periods delay patient access to lower-priced medications, and policymakers should consider options to encourage timely competition, particularly among biologic drugs.
Subject(s)
Biosimilar Pharmaceuticals/economics , Drug Approval/economics , Drugs, Generic/economics , Prescription Drugs/economics , Cohort Studies , Drug Costs , Drug Industry/economics , Economic Competition/economics , Humans , MotivationABSTRACT
Biosimilars are the biological drugs that are granted after the expiry of the patent of an affirmed innovator. Asia Pacific countries are characterized by significant demand as they account for majority of the world population and poor affordability due to low per capita income in most regions. Some of these countries offer potential to emerge as global suppliers of affordable, safe and efficacious biosimilars. This article highlights the prospects of biosimilars in the Asia Pacific market. Regulatory framework in the various countries is also discussed.
Subject(s)
Biosimilar Pharmaceuticals/economics , Biosimilar Pharmaceuticals/supply & distribution , Drug Approval/economics , Drug Approval/legislation & jurisprudence , Drug Industry/economics , Drug Industry/legislation & jurisprudence , Asia, Southeastern , Asia, Western , Asia, Eastern , Humans , Marketing/economics , Marketing/legislation & jurisprudenceABSTRACT
Importance: The growth of cancer drug spending in the US has outpaced spending in nearly all other sectors, and an increasing proportion of the drug development pipeline is devoted to oncology. In 2018, there was a record number of drugs entering the US market. Objective: To estimate the number of patients with cancer who are eligible for the newly approved drug-indication pairs, and project potential spending and use of the approvals in the US. Design, Setting, Participants: This is a retrospective review of 2018 US Food and Drug Administration (FDA) oncology drug approvals with estimation of the eligible population. The cost of new therapy was estimated, and savings from displaced therapies were subtracted. Two-way sensitivity analysis explored uncertainty in pricing and market diffusion. Data were collected between March 1, 2019, and September 30, 2019. Exposures: Data related to the cancer drug approval (ie, indications, approval pathway, basis for approval), cancer incidence, and drug price were extracted from publicly available sources, including the FDA, National Cancer Institute, and American Cancer Society websites, as well as the RED BOOK database. Main Outcomes and Measures: The primary outcome was the projected net expenditure in the US associated with the new therapies. The secondary outcome described how variable market diffusion and pricing permit expected levels of spending. Results: A total of 46 oncology approvals were included in the analysis, with 17 novel drugs and 29 new indications. The average price per patient per treatment course was $150â¯384. From a national perspective and with 100% market diffusion, the projected net expenditure for newly approved drugs was $39.5 billion per year. To maintain the recent trend of cancer drug spending, the 2018 cancer drug approvals need to be used in fewer than 20% of eligible patients. Conclusions and Relevance: New cancer drugs approved by the FDA in 2018 would drastically increase cancer drug spending in the US if used widely. Alternatively, only low-level use of the new drugs is consistent with market forecasting.
Subject(s)
Antineoplastic Agents/economics , Drug Approval/economics , Humans , Medical Oncology , Neoplasms/drug therapy , Retrospective Studies , United States , United States Food and Drug AdministrationSubject(s)
Anti-Bacterial Agents/economics , Anti-Bacterial Agents/supply & distribution , Drug Industry/economics , Tetracyclines/economics , Administration, Intravenous , Administration, Oral , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/microbiology , Drug Approval/economics , Drug Approval/statistics & numerical data , Drug Resistance, Microbial , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/microbiology , Tetracyclines/administration & dosage , Tetracyclines/therapeutic use , Tigecycline/administration & dosage , Tigecycline/economics , Tigecycline/therapeutic use , United States , United States Food and Drug AdministrationABSTRACT
In spring 2018, the American Heart Association convened the Value in Healthcare Summit to begin an important conversation about the challenges patients with cardiovascular disease face in accessing and deriving quality and value from the healthcare system. Following the summit and recognizing the collective momentum it created, the American Heart Association, in collaboration with the Robert J. Margolis Center for Health Policy at Duke University, launched the Value in Healthcare Initiative-Transforming Cardiovascular Care. Four areas of focus were identified, and learning collaboratives were established and proceeded to conduct concrete, actionable problem solving in 4 high-impact areas in cardiovascular care: Value-Based Models, Partnering with Regulators, Predict and Prevent, and Prior Authorization. The deliverables from these groups are being disseminated in 4 stand-alone articles, and their publication will initiate further work to test and evaluate each of these promising areas of reform. This article provides an overview of the initiative's findings and highlights key cross-cutting themes for consideration as the initiative moves forward.