Exposure to US Cancer Drugs With Lack of Confirmed Benefit After US Food and Drug Administration Accelerated Approval

Parikh, Ravi B.; Hubbard, Rebecca A.; Wang, Erkuan; Royce, Trevor J.; Cohen, Aaron B.; Clark, Amy S.; Mamtani, Ronac

doi:10.1001/jamaoncol.2022.7770

Cited by 9 publications

(4 citation statements)

References 4 publications

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“…Oncology drugs have increasingly been approved with provisional evidence of efficacy which often remain on the market after failure of confirmatory trials. [36][37][38] When drug approval processes do not clarify a drug's therapeutic value, this task is deferred to point-of-care utilization management processes. 39 The ongoing presence of unproven or disproven drugs in the market suggests that there are important and necessary applications of prior authorization to protect patients from costly, low-value care.…”

Section: Discussionmentioning

confidence: 99%

Prior Authorization and Association With Delayed or Discontinued Prescription Fills

Kyle,

Keating

2024

JCO

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PURPOSE Prior authorization requirements are increasing but little is known about their effects on access to care. We examined the association of a new prior authorization policy with delayed or discontinued prescription fills for oral anticancer drugs among Medicare Part D beneficiaries. METHODS Using Medicare part D claims data from 2010 to 2020, we studied beneficiaries regularly filling one of 11 oral anticancer drugs, defined as three 30-day fills in 120 days preceding the plan's prior authorization policy change on that drug and continuously enrolled in the same plan for 120 days before and after the policy change at the start of a new year. The control group consisted of beneficiaries meeting the same utilization criteria, but who were enrolled in plans at the same time that did not implement a prior authorization policy change. The outcomes of interest were discontinuation of the drug within 120 days (analyzed with regression analyses) and time (in days) to next fill after a prior authorization policy change (analyzed using a quasi-experimental difference-in-differences event study). RESULTS The introduction of a new prior authorization on an established drug increased the odds of discontinuation within 120 days (adjusted odds ratio, 7.1 [95% CI, 6.0 to 8.5]; P < .001) and increased time to next fill by 9.7 days (95% CI, 8.2 to 11.2; P < .001), relative to patients whose plans did not have a prior authorization policy change. CONCLUSION Introduction of a new prior authorization policy on an established drug regimen is associated with increased probability of discontinued and delayed care. For some conditions, this may represent a clinically consequential barrier to access. Waiving prior authorization for patients already established on a drug may improve adherence.

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Section: Discussionmentioning

confidence: 99%

Prior Authorization and Association With Delayed or Discontinued Prescription Fills

Kyle,

Keating

2024

JCO

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“…Second, although this study was conducted with a minimum of 5 years of follow-up for the clinical benefit cohort, 7 drugs were still awaiting confirmatory trial results, and these drugs may yet show benefit. However, patients receiving these drugs still receive interventions of uncertain clinical efficacy in the meantime . Third, because published overall survival and quality-of-life data were relied on in this study and primary data were not reevaluated, it is possible that clinical benefit may have been overestimated because statistical improvements in end points may or may not be clinically meaningful to patients depending on magnitude and methodologic approach (eg, trial population differs from real-world patients, control group offered substandard care, differential survey response rates).…”

Section: Discussionmentioning

confidence: 99%

Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval

Liu,

Kesselheim,

Cliff

2024

JAMA

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ImportanceThe US Food and Drug Administration’s (FDA) accelerated approval pathway allows approval of investigational drugs treating unmet medical needs based on changes to surrogate measures considered “reasonably likely” to predict clinical benefit. Postapproval clinical trials are then required to confirm whether these drugs offer clinical benefit.ObjectiveTo determine whether cancer drugs granted accelerated approval ultimately demonstrate clinical benefit and to evaluate the basis of conversion to regular approval.Design, Setting, and ParticipantsIn this cohort study, publicly available FDA data were used to identify cancer drugs granted accelerated approval from 2013 to 2023.Main Outcomes and MeasuresDemonstrated improvement in quality of life or overall survival in accelerated approvals with more than 5 years of follow-up, as well as confirmatory trial end points and time to conversion for drug-indication pairs converted to regular approval.ResultsA total of 129 cancer drug–indication pairs were granted accelerated approval from 2013 to 2023. Among 46 indications with more than 5 years of follow-up (approved 2013-2017), approximately two-thirds (29, 63%) were converted to regular approval, 10 (22%) were withdrawn, and 7 (15%) remained ongoing after a median of 6.3 years. Fewer than half (20/46, 43%) demonstrated a clinical benefit in confirmatory trials. Time to withdrawal decreased from 9.9 years to 3.6 years, and time to regular approval increased from 1.6 years to 3.6 years. Among 48 drug-indication pairs converted to regular approval, 19 (40%) were converted based on overall survival, 21 (44%) on progression-free survival, 5 (10%) on response rate plus duration of response, 2 (4%) on response rate, and 1 (2%) despite a negative confirmatory trial. Comparing accelerated and regular approval indications, 18 of 48 (38%) were unchanged, while 30 of 48 (63%) had different indications (eg, earlier line of therapy).Conclusions and RelevanceMost cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes.

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“…51 The prolonged use of cancer drugs without proven clinical benefit may expose patients to high costs and ineffective treatments. 52 , 53 In another study, it was reported that for cancer drugs that initiated confirmatory clinical trials at the time of AA, the median time to complete confirmatory clinical trials and then move to regular approval was 3 years, significantly less than the 5.1 years to initiate confirmatory clinical trials after AA. 54 Similarly, this finding was also confirmed for non-oncology drugs that received AA.…”

Section: Discussionmentioning

confidence: 99%

Evidence of pre-approval clinical trial supporting the granted conditional approval for novel cancer drugs in China between 2015 and 2022

Luo,

Du,

Huang

et al. 2023

eClinicalMedicine

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Exposure to US Cancer Drugs With Lack of Confirmed Benefit After US Food and Drug Administration Accelerated Approval

Abstract: This cross-sectional study evaluates patient exposure to oncology drugs withdrawn from the US Food and Drug Administration (FDA) Accelerated Approval program.

Cited by 9 publications

References 4 publications

Prior Authorization and Association With Delayed or Discontinued Prescription Fills

Prior Authorization and Association With Delayed or Discontinued Prescription Fills

Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval

Evidence of pre-approval clinical trial supporting the granted conditional approval for novel cancer drugs in China between 2015 and 2022

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