Trial-level factors affecting accrual and completion of oncology clinical trials: A systematic review

Hauck, Cherie L; Kelechi, Teresa J.; Cartmell, Kathleen B.; Mueller, Martina

doi:10.1016/j.conctc.2021.100843

Cited by 17 publications

(10 citation statements)

References 28 publications

(75 reference statements)

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“…The median months for participant accrual into the study was 22 months for randomised (IQR: 16-27) and 22 months non-randomised (IQR: 74-206) studies. However, accrual rate differed between study cohorts (randomised (IQR): 22 (15-36); non-randomised: 5 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)). Of the total 133 randomised trials, 36 (27%) had OS and 72 (54%) had PFS as a primary endpoint, whereas, of the 61 nonrandomised studies, 58 (97%) listed response rate as the primary endpoint.…”

Section: Resultsmentioning

confidence: 99%

“… 14 We build on a previous systematic review for trial-level factors affecting accrual and completion of oncology clinical trials. 6 Further variables were added through expertise of the study team. The first explanatory variable was ‘primary endpoint’.…”

Section: Methodsmentioning

confidence: 99%

“…3 It is estimated 20%-40% of trials investigating new cancer medicines close due to inadequate participant accrual. [3][4][5][6][7] Given the challenge of participant recruitment in clinical trials, several studies have highlighted barriers to participation. 2 5 6 8 9 Recent literature suggests certain design features as eligibility criteria, randomisation, trial phase, study type, line of therapy, sample size, treatment type and incidence of disease impact may impact study accrual and ultimately completion of oncology trials.…”

Section: Introductionmentioning

confidence: 99%

“…2 5 6 8 9 Recent literature suggests certain design features as eligibility criteria, randomisation, trial phase, study type, line of therapy, sample size, treatment type and incidence of disease impact may impact study accrual and ultimately completion of oncology trials. 6 As such, methods to improve recruitment to clinical trials is gaining interest. 10 Prior work has developed models to identify predictors of accrual in varying settings with mixed results.…”

Section: Introductionmentioning

confidence: 99%

“…The most common reason for a trial to close prematurely is poor accrual 3. It is estimated 20%–40% of trials investigating new cancer medicines close due to inadequate participant accrual 3–7…”

Section: Introductionmentioning

confidence: 99%

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What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020)

et al. 2022

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ObjectiveTo examine factors associated with accrual rate in industry sponsored clinical trials supporting US Food and Drug Administration (FDA) cancer drug approvals from 2015 to 2020.Design, setting and participantsRetrospective cross-sectional study included 194 pivotal trials supporting cancer drug approvals by the US FDA from 2015 to 2020.InterventionsClinical trials were analysed for the type of blinding, primary endpoint, whether crossover was specified in the publication, study phase, line of therapy, response rate, investigational sites, manufacturer and randomisation ratio.Main outcome measuresThe main outcome was the rate of accrual, which is the number of patients accrued in the study per open month of enrolment.ResultsThe study consisted of 133 randomised (68%) and 61 (32%) non-randomised clinical trials. In randomised studies, we found the accrual rate was higher in trials investigating first and second line drugs (adjusted rate ratios (aRR): 1.55, 95% CI 1.18 to 2.09), phase III trials (aRR: 2.13, 95% CI 1.48 to 2.99), and for studies sponsored by Merck (aRR: 1.47, 95% CI 1.18 to 2.37), adjusting for other covariates. In contrast, the primary endpoint of a study, presence of crossover, single agent response rate, the number of investigational sites, population disease burden and skewed randomisation ratios were not associated with the rate of accrual. In the non-randomised adjusted model, the accrual rate was 2.03 higher (95% CI 1.10 to 3.92) for clinical trials sponsored by manufacturer, specifically Merck. Primary endpoint, crossover, trial phase, response rate, the number of investigational sites, disease burden or line of therapy were not associated with the rate of accrual.ConclusionIn this cross-sectional study, line of therapy, study phase and manufacturer were the only factors associated with accrual rate. These findings suggest many proffered factors for speedy trial accrual are not associated with greater enrolment rates.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020)

et al. 2022

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Special FDA designations for drug development: orphan, fast track, accelerated approval, priority review, and breakthrough therapy

Michaeli,

Albers

et al. 2023

Eur J Health Econ

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Background Over the past decades, US Congress enabled the US Food and Drug Administration (FDA) to facilitate and expedite drug development for serious conditions filling unmet medical needs with five special designations and review pathways: orphan, fast track, accelerated approval, priority review, and breakthrough therapy. Objectives This study reviews the FDA’s five special designations for drug development regarding their safety, efficacy/clinical benefit, clinical trials, innovation, economic incentives, development timelines, and price. Methods We conducted a keyword search to identify studies analyzing the impact of the FDA's special designations (orphan, fast track, accelerated approval, priority review, and breakthrough therapy) on the safety, efficacy/clinical benefit, trials, innovativeness, economic incentives, development times, and pricing of new drugs. Results were summarized in a narrative overview. Results Expedited approval reduces new drugs’ time to market. However, faster drug development and regulatory review are associated with more unrecognized adverse events and post-marketing safety revisions. Clinical trials supporting special FDA approvals frequently use small, non-randomized, open-label designs. Required post-approval trials to monitor unknown adverse events are often delayed or not even initiated. Evidence suggests that drugs approved under special review pathways, marketed as “breakthroughs”, are more innovative and deliver a higher clinical benefit than those receiving standard FDA approval. Special designations are an economically viable strategy for investors and pharmaceutical companies to develop drugs for rare diseases with unmet medical needs, due to financial incentives, expedited development timelines, higher clinical trial success rates, alongside greater prices. Nonetheless, patients, physicians, and insurers are concerned about spending money on drugs without a proven benefit or even on drugs that turn out to be ineffective. While European countries established performance- and financial-based managed entry agreements to account for this uncertainty in clinical trial evidence and cost-effectiveness, the pricing and reimbursement of these drugs remain largely unregulated in the US. Conclusion Special FDA designations shorten clinical development and FDA approval times for new drugs treating rare and severe diseases with unmet medical needs. Special-designated drugs offer a greater clinical benefit to patients. However, physicians, patients, and insurers must be aware that special-designated drugs are often approved based on non-robust trials, associated with more unrecognized side effects, and sold for higher prices.

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Patient Enrollment per Month (Accrual) in Clinical Trials Leading to the FDA Approval of New Cancer Drugs

Michaeli,

Albers

et al. 2024

Targ Oncol

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Trial-level factors affecting accrual and completion of oncology clinical trials: A systematic review

Cited by 17 publications

References 28 publications

What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020)

What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020)

Special FDA designations for drug development: orphan, fast track, accelerated approval, priority review, and breakthrough therapy

Patient Enrollment per Month (Accrual) in Clinical Trials Leading to the FDA Approval of New Cancer Drugs

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