IMPORTANCEIn recent years, drug approvals have been based on fewer, smaller, and less rigorous pivotal trials. Less robust preapproval testing raises questions about the efficacy and clinical value of these drugs. OBJECTIVE To assess the regulatory context, pivotal design characteristics, and postmarket requirements (PMRs) and postmarket commitments (PMCs) of novel 2020 drug approvals to characterize the state of evidence at the time of approval. DESIGN, SETTING, AND PARTICIPANTS This cohort study identified novel drugs approved by the US Food and Drug Administration's (FDA) Center for Drug Evaluation and Research in 2020. The Drugs@FDA database was used to extract key characteristics of each drug's pivotal trials. Drug approval packages provided regulatory information. The prevalence of key trial design features was compared between oncology and nononcology drugs. EXPOSURES Drug names, date of approval, indication on labeling, and clinical and regulatory details. MAIN OUTCOMES AND MEASURES Number of pivotal trials, pivotal trial design (randomization, masking, groups), trial comparator, trial hypothesis, trial end points, results, number and type of expedited pathway designations, and number and type of PMRs and PMCs. RESULTSThe 49 novel therapeutics approved in 2020 were supported by 75 pivotal trials. More than half of drugs (28 [57.1%]) were supported by a single pivotal trial. Trial sizes ranged from 19 to 2230 participants. More than three-fourths of trials (57 [76.0%]) had a randomization component, and nearly two-thirds (46 [61.3%]) were double-masked. Most used a superiority approach. Roughly half (39 [52.0%]) compared the novel therapeutic with a placebo or vehicle control; 13 (17.3%), an active control; 2 (2.7%), both a placebo and active control; and 21 (28.0%), a historical, external, or other control. Nearly half of pivotal trials (34 [45.3%]) used a surrogate measure as a primary end point. Pivotal trials supporting oncology approvals were much more likely to have historical controls than nononcology approvals (13 of 18 [72.2%] vs 8 of 57 [14.0%]; P < .001) and to use at least 1 surrogate measure as a primary end point (17 [94.4%] vs 17 [29.8%]; P < .001). Forty drugs had at least 1 PMR or PMC, accounting for 178 PMRs and PMCs across the cohort. CONCLUSIONS AND RELEVANCEThese findings suggest that the increased flexibility in the characteristics of acceptable preapproval evidence can be partially explained by the increase in trials of drugs for rare and other serious conditions that require flexible testing strategies as well as the associated regulatory changes that have accumulated over time. The FDA and consumers may (continued) Key Points Question What were the key design characteristics of the pivotal trials supporting novel drugs approved by the US Food and Drug Administration (FDA) in 2020? Findings This cohort study of 49 drugs approved by the FDA in 2020 found that they were supported by 75 pivotal trials, of which nearly two-thirds were double-masked, more than threefourths had a randomiz...
ImportanceDrug expenditures in the US are higher than in any other country and are projected to continue increasing, so US health systems may benefit from evaluating international regulatory and reimbursement decision-making of new drugs.ObjectiveTo evaluate regulatory decisions and health technology assessments (HTAs) in Australia, Canada, and the UK regarding new drugs approved by the US Food and Drug Administration (FDA) in 2017 through 2020, as well as to estimate the US cost per patient per year for drugs receiving negative recommendations.Design and SettingIn this cross-sectional study, recommendations issued by agencies in Australia, Canada, and the UK were collected for new drugs approved by the FDA in 2017 through 2020. All data were current as of May 31, 2022.ExposuresAuthorizations and HTAs in selected countries.Main Outcomes and MeasuresAll FDA-approved drugs were matched by active ingredient to decision summary reports published by drug regulators and HTA agencies in Australia, Canada, and the UK. Regulatory approval concordance and reasons for negative recommendations were assessed using descriptive statistics. For drugs not recommended by an international agency, the annual US drug cost per patient was estimated from FDA labeling and wholesale acquisition costs.ResultsThe FDA approved 206 new drugs in 2017 through 2020, of which 162 (78.6%) were granted marketing authorization by at least 1 other regulatory agency at a median (IQR) delay of 12.1 (17.7) months following US approval. Conversely, 5 FDA-approved drugs were refused marketing authorization by an international regulatory agency due to unfavorable benefit-to-risk assessments. An additional 42 FDA-approved drugs received negative reimbursement recommendations from HTA agencies in Australia, Canada, or the UK due to uncertainty of clinical benefits or unacceptably high prices. The median (IQR) US cost of the 47 drugs refused authorization or not recommended for reimbursement by an international agency was $115 281 ($166 690) per patient per year. Twenty drugs were for oncology indications, and 36 were approved by the FDA through expedited regulatory pathways or the Orphan Drug Act.Conclusions and RelevanceThis cross-sectional study assessed reasons for which drugs recently approved by the FDA were refused marketing authorization or not recommended for public reimbursement in other countries. Drugs with limited international market presence may require close examination by US health care professionals and health systems.
3552 Background: Bevacizumab-awwb was the first biosimilar approved by the U.S. Food and Drug Administration (FDA) for treatment of cancer and became available for use in July 2019. Clinical comparative efficacy and safety of bevacizumab-awwb to bevacizumab was established in a single study of adult patients with advanced non-squamous non-small cell lung cancer. Approval based on extrapolation was granted by the FDA for all other indications, including metastatic colorectal cancer (mCRC). The objective of this study was to evaluate the real-world effectiveness and safety outcomes of patients with mCRC initiated on bevacizumab-awwb versus bevacizumab in an integrated healthcare delivery system. Methods: This was an observational cohort study of patients with mCRC in Kaiser Permanente California, Colorado, and Mid-Atlantic States who were initiated on bevacizumab-awwb between July 2019 and March 2020 or reference bevacizumab between July 2015 and June 2018. Patients with history of bevacizumab use in the 6 months prior to the index treatment date were excluded. Patients were followed until 12 months after treatment initiation, end of plan membership, or death, whichever occurred first. The primary outcome of overall survival (OS) was analyzed using a non-inferiority test with lower margin of 10% and Cox proportional-hazards modeling. Secondary outcomes included count of doses received, treatment duration, all-cause hospitalizations, and incidence of serious adverse events. Results: A total of 1,445 patients initiated on either bevacizumab-awwb (n=239) or bevacizumab (n=1,206) were included in the analysis. The mean overall age was 60 ± 13 years and 54% of patients were male. The OS rate was 72.8% and 73.1% for patients receiving bevacizumab-awwb and bevacizumab, respectively ( p<0.01 for non-inferiority). The adjusted hazard ratio for mortality was 1.01 (0.77-1.33, p=0.93). There were no statistically significant differences in secondary outcomes between the 2 study groups (Table). Conclusions: Bevacizumab-awwb is a safe and effective option when compared to the reference bevacizumab in the treatment of mCRC. Future studies should evaluate outcomes after longer follow-up time and in different cancer types. [Table: see text]
This cohort study used the Drugs@FDA database to identify new drugs approved by the US Food and Drug Administration (FDA) and assess fulfillment of postmarket commitments and requirements.
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