Impact of Expanded Access on FDA Regulatory Action and Product Labeling

Jarow, Jonathan P.; Moscicki, Richard A.

doi:10.1177/2168479017707800

Cited by 16 publications

(11 citation statements)

References 6 publications

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“…In reality, the latter fear appears unfounded. Over 10-years, only two out of 11,000 EAP requests to the FDA resulted in a clinical hold being placed on the development of a commercial drug due to adverse events, and in both cases, the development continued after the issues were addressed ( 24 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

Early access provision: Awareness, educational needs and opportunities to improve oncology patients’ access to care

Krendyukov

Singhvi²,

Green-Morrison³

et al. 2022

Front. Oncol.

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BackgroundAn unmet medical need exists for many oncology patients who cannot be treated satisfactorily by available therapeutic options. Early access provision (EAP) is endorsed by competent authorities to improve patient access to innovative medicinal products (InMPs). This paper determined awareness and understanding among practicing physicians of integrated EAP protocols, and of the procedures involved in EAP applications for oncology trials prior to marketing authorization.MethodsAn on-line, fully anonymous survey reaching out to more than 3,258 physicians (including practicing oncologists) was initiated between November 2020 - January 2021. Participants were questioned about their knowledge and understanding of EAP and the decision processes involved, level of experience, interest for further educational activities and opportunities to improve the process, both in general and specifically during the COVID-19 pandemic. The frequency of EAP protocols for oncology InMPs was identified by a search of ClinicalTrials.gov and EU Clinical Trials registers.ResultsSurvey results (75% oncologists) indicated 75% of respondents were ‘very comfortable’ or ‘comfortable’ with using EAP for their patients, but only 54.5% correctly answered the specific knowledge-based question related to the EAP definition. For 56% of respondents, experience with EAP in daily practice was very limited. Two-thirds indicated an average or lower level of understanding about the application process and regulatory requirements involved (65.2% and 66.0%, respectively). Knowledge on data collection and serious adverse event reporting under EAP was lower at 57.8% and 50.5% of respondents, respectively. Awareness of physician responsibilities was high in 59.7% of respondents, but fewer understood roles and responsibilities of manufacturing companies (31.2%). Most indicated they would consider clinical efficacy and safety data from comparative phase III randomized controlled trials as of high importance to support their decision to apply for EAP (93.4% and 86.8%, respectively). During the COVID-19 pandemic, the majority of respondents highlighted the need to improve and adapt EAP with regard to the application process and documentation (83.8%), InMP supply and logistics (88.4), and safety reporting process (78.0%). Of identified oncology trials with a ClinicalTrials.gov protocol, only 149 (0.4%) included EAP, and 23 used the data to receive a marketing authorization during the period Jan 2015 to December 2020. Of oncology trials with a EudraCT protocol, only 21 (0.23%) included EAP, of which 6 were used to receive a conditional or full marketing authorisation over the same period.ConclusionUse of EAP in daily practice remains limited. Challenges posed by the EAP process, together with a lack of education on this topic, might contribute to its under-utilization and influence access of oncology patients to care. Continuous educational efforts from different stakeholders are required to better inform and support practicing oncologists during the EAP application process and regulatory framework follow up. Education should also be provided on EAP roles and responsibilities, monitoring, and potential adaptations when faced with specific challenges, such as the current COVID-19 pandemic.

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Section: Discussionmentioning

confidence: 99%

Early access provision: Awareness, educational needs and opportunities to improve oncology patients’ access to care

Krendyukov

Singhvi²,

Green-Morrison³

et al. 2022

Front. Oncol.

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“…If a substantial number of such studies have not been registered, then some measures should be introduced to enforce higher compliance. It is noteworthy that FDA-affiliated authors have already published some reports on expanded access based on the data contained in expanded access requests submitted to the FDA [ 19 - 21 ].…”

Section: Discussionmentioning

confidence: 99%

ClinicalTrials.gov as a Source of Information About Expanded Access Programs: Cohort Study

Borysowski

Górski

2021

J Med Internet Res

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Background ClinicalTrials.gov (CT.gov) is the most comprehensive internet-based register of different types of clinical studies. Expanded access is the use of unapproved drugs, biologics, or medical devices outside of clinical trials. One of the key problems in expanded access is the availability to both health care providers and patients of information about unapproved treatments. Objective We aimed to evaluate CT.gov as a potential source of information about expanded access programs. Methods We assessed the completeness of information in the records of 228 expanded access programs registered with CT.gov from February 2017 through May 2020. Moreover, we examined what percentage of published expanded access studies has been registered with CT.gov. Logistic regression (univariate and multivariate) and mediation analyses were used to identify the predictors of the absence of some information and a study’s nonregistration. Results We found that some important data were missing from the records of many programs. Information that was missing most often included a detailed study description, facility information, central contact person, and eligibility criteria (55.3%, 54.0%, 41.7%, and 17.5% of the programs, respectively). Multivariate analysis showed that information about central contact person was more likely to be missing from records of studies registered in 2017 (adjusted OR 21.93; 95% CI 4.42-172.29; P<.001). This finding was confirmed by mediation analysis (P=.02). Furthermore, 14% of the programs were registered retrospectively. We also showed that only 33 of 77 (42.9%) expanded access studies performed in the United States and published from 2014 through 2019 were registered with CT.gov. However, multivariate logistic regression analysis showed no significant association between any of the variables related to the studies and the odds of study nonregistration (P>.01). Conclusions Currently, CT.gov is a quite fragmentary source of data on expanded access programs. This problem is important because CT.gov is the only publicly available primary source of information about specific programs. We suggest the actions that should be taken by different stakeholders to fully exploit this register as a source of information about expanded access.

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“…[11][12][13][14][15] In particular, drug company participation in EA may be limited due to administrative burden, as EA can require significant human resources. 12 There is a need to improve awareness about processes and procedures for seeking EA [16][17][18] and better enforce Cures Act EA policy requirements. For example, currently, the Act does not appear to specify a penalty for noncompliance.…”

Section: Articlementioning

confidence: 99%

Implementation of 21st Century Cures Act Expanded Access Policies Requirements

Kang

Chang

Ross

et al. 2021

Clin Pharma and Therapeutics

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The US Food and Drug Administration (FDA) expanded access pathway allows patients with life-threatening or serious conditions to access investigational drugs outside of trials, under certain conditions. The 21st Century Cures Act ("Cures Act") requires certain drug companies to publicly disclose their expanded access policies. We characterized the proportion of applicable US biopharmaceutical companies, with an oncology related drug, implementing Cures Act requirements for expanded access policies and whether available policies contain the information described in the Act. We found about one-third of applicable biopharmaceutical companies (32%, 140/423) implemented the Cures Act requirement to have a public expanded access policy. Less than one-third of public policies contained all described information (31%, 44/140). Larger companies and those with at least one drug receiving an FDA expedited designation (59% vs. 21%; P < 0.001), or at least one FDA-approved drug (57% vs. 28%; P < 0.001) were more likely to have a public policy. Our results suggest the Cures Act may be having a limited impact on its goals of supporting timely medical decisions and closing informational gaps for patients and doctors around expanded access to investigational oncology therapies, especially for products sponsored by smaller and newer companies.The US Food and Drug Administration (FDA) expanded access (EA) pathway, sometimes also called compassionate use, is a route for patients with immediately life-threatening or serious diseases or conditions to potentially access experimental medicines outside of clinical trials. To qualify, patients must be unable to enroll in a relevant clinical trial, have no comparable satisfactory alternative FDA approved therapy options, and be deemed more likely to experience benefit than risk from the unapproved intervention. Additionally, expanded access provisions should not threaten a product's development program (e.g., trial enrollment). Formalized in 1987, in the context of the AIDS epidemic, the EA pathway has been amended multiple times, most recently in 2016 through section 561 of the Food, Drug, and Cosmetics Act (FDCA), as a part of the 21st Century Cures Act ("Cures Act").The Cures Act aimed to help increase awareness among patients and clinicians about the processes and procedures for accessing

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Impact of Expanded Access on FDA Regulatory Action and Product Labeling

Cited by 16 publications

References 6 publications

Early access provision: Awareness, educational needs and opportunities to improve oncology patients’ access to care

Early access provision: Awareness, educational needs and opportunities to improve oncology patients’ access to care

ClinicalTrials.gov as a Source of Information About Expanded Access Programs: Cohort Study

Implementation of 21st Century Cures Act Expanded Access Policies Requirements

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