Characteristics of Cost-effectiveness Studies for Oncology Drugs Approved in the United States From 2015-2020.

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.

An urgent call to raise the bar in oncology.

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.

CFTR modulators: transformative therapies for cystic fibrosis.

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.

The effectiveness and value of novel treatments for cystic fibrosis.

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.

Market Exclusivity Length for Drugs with New Generic or Biosimilar Competition, 2012-2018.

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.

Potential Cost Implications for All US Food and Drug Administration Oncology Drug Approvals in 2018.

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 $150 384. 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.

Regulatory considerations in biosimilars: Asia pacific regions.

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.

Value in Healthcare Initiative: Summary and Key Recommendations.

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.

Variation in the estimated costs of pivotal clinical benefit trials supporting the US approval of new therapeutic agents, 2015-2017: a cross-sectional study.

OBJECTIVES: Little is routinely disclosed about the costs of the pivotal clinical trials that provide the key scientific evidence of the treatment benefits of new therapeutic agents. We expand our earlier research to examine why the estimated costs may vary 100-fold. DESIGN: A cross-sectional study of the estimated costs of the pivotal clinical trials supporting the approval of 101 new therapeutic agents approved by the US Food and Drug Administration from 2015 to 2017. METHODS: We licensed a software tool used by the pharmaceutical industry to estimate the likely costs of clinical trials to be conducted by contract research organisations. For each trial we collected 52 study characteristics. Linear regression was used to assess the most important factors affecting costs. PRIMARY AND SECONDARY OUTCOME MEASURES: The mean and 95% CI of 225 pivotal clinical trials using varying assumptions. We also assessed median estimated costs per patient, per clinic visit and per drug. RESULTS: Measured as pivotal trials cost per approved drug, the 101 new molecular entities had an estimated median cost of US$48 million (IQR US$20 million-US$102 million). The 225 individual clinical trials had a median estimate of US$19 million (IQR US$12 million-US$33 million) per trial and US$41 413 (IQR, US$29 894-US$75 047) per patient. The largest single factor driving cost was the number of patients required to establish the treatment effects and varied from 4 patients to 8442. Next was the number of trial clinic visits, which ranged from 2 to 166. Our statistical model showed trial costs rose exponentially with these two variables (R2=0.696, F=257.9, p<0.01). CONCLUSIONS: The estimated costs are modest for measuring the benefits of new therapeutic agents but rise exponentially as more patients and clinic visits are required to establish a drug effect.

Insurance Denials of Care Amount to Unlicensed Medical Practice.

DISCLOSURES: No funding supported the writing of this article. The author has nothing to disclose.

Pharmaceutical Company Payments to Japanese Government Drug Regulation Committee Members.

Little is known about the characteristics and distribution of financial conflicts of interest (FCOIs) in the drug regulation process, both in Japan and globally. This study aimed to identify the characteristics and distribution of pharmaceutical payments to members of Japanese government drug regulation committees, and to assess the accuracy of their FCOI statements. Among members who worked for either of the five committees of the Pharmaceutical Affairs and Food Sanitation Council (PAFSC), which is the advisory committee for pharmaceutical affairs in Japan, from April 1, 2017 to March 31, 2019, the extent of payments in 2016 from 78 major pharmaceutical companies in Japan and the accuracy of the self-reported FCOI disclosures were assessed. Of 108 members, 54 (50%) were medical doctors. The payments to the PAFSC members totaled ¥115,765,006 ($1,064,017), and the mean (SD) payment was ¥1,071,898 ($9,852) (¥2,272,520 ($20,887)). Fifty-one members (47%) received at least one payment from a pharmaceutical company in 2016; 32 members (30%) received more than ¥500,000 ($4,600). Of 8,530 declarations from five councils, 409 (4.8%) of the FCOIs self-reported by the committee members were inaccurate. Of those inaccurate disclosures, 112 of 409 inaccurate disclosures (27.4%) would have prevented the recipients from participating in the drug-approval decision-making processes had they been correctly disclosed. Almost half of drug regulation committee members in Japan received at least one payment from pharmaceutical companies in 2016. Moreover, several FCOIs they reported were inaccurate.

Benchmarking biopharmaceutical process development and manufacturing cost contributions to R&D.

This study aims to benchmark and analyze the process development and manufacturing costs across the biopharmaceutical drug development cycle and their contribution to overall research and development (R&D) costs. This was achieved with a biopharmaceutical drug development lifecycle cost model that captured the costs, durations, risks and interdependencies of the clinical, process development and manufacturing activities. The budgets needed for process development and manufacturing at each phase of development to ensure a market success each year were estimated. The impact of different clinical success rate profiles on the process development and manufacturing costs at each stage was investigated, with a particular focus on monoclonal antibodies. To ensure a market success each year with an overall clinical success rate (Phase I to approval) of ~12%, the model predicted that a biopharmaceutical company needs to allocate process development and manufacturing budgets in the order of ~$60 M for pre-clinical to Phase II material preparation and ~$70 M for Phase III to regulatory review material preparation. For lower overall clinical success rates of ~4%, which are more indicative of diseases such as Alzheimer's, these values increase to ~$190 M for early-phase and ~$140 Mfor late-phase material preparation; hence, the costs increase 2.5 fold. The costs for process development and manufacturing per market success were predicted to represent 13-17% of the R&D budget from pre-clinical trials to approval. The results of this quantitative structured cost study can be used to aid decision-making during portfolio management and budget planning procedures in biopharmaceutical development.

A novel method for predicting the budget impact of innovative medicines: validation study for oncolytics.

BACKGROUND: High budget impact (BI) estimates of new drugs have led to decision-making challenges potentially resulting in restrictions in patient access. However, current BI predictions are rather inaccurate and short term. We therefore developed a new approach for BI prediction. Here, we describe the validation of our BI prediction approach using oncology drugs as a case study. METHODS: We used Dutch population-level data to estimate BI where BI is defined as list price multiplied by volume. We included drugs in the antineoplastic agents ATC category which the European Medicines Agency (EMA) considered a New Active Substance and received EMA marketing authorization (MA) between 2000 and 2017. A mixed-effects model was used for prediction and included tumor site, orphan, first in class or conditional approval designation as covariates. Data from 2000 to 2012 were the training set. BI was predicted monthly from 0 to 45 months after MA. Cross-validation was performed using a rolling forecasting origin with e^|Ln(observed BI/predicted BI)| as outcome. RESULTS: The training set and validation set included 25 and 44 products, respectively. Mean error, composed of all validation outcomes, was 2.94 (median 1.57). Errors are higher with less available data and at more future predictions. Highest errors occur without any prior data. From 10 months onward, error remains constant. CONCLUSIONS: The validation shows that the method can relatively accurately predict BI. For payers or policymakers, this approach can yield a valuable addition to current BI predictions due to its ease of use, independence of indications and ability to update predictions to the most recent data.