Retrospective evaluation of single patient investigational new drug (IND) requests in pediatric oncology

Shulman, David S.; Kiwinda, Lulla V; Edwards, Stacey L.; Clinton, Catherine; Hunt, Sarah K.; Greenspan, Lianne; Lawler, Kristen; Reaman, Gregory H.; Al‐Sayegh, Hasan; Bona, Kira; O’Neill, Allison F.; Shusterman, Suzanne; Janeway, Katherine A.; Place, Andrew E.; Susan, N.; Ma, Clement; DuBois, Steven G.

doi:10.1002/cam4.3791

Cited by 8 publications

(6 citation statements)

References 20 publications

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“…There is a strong consensus that the involvement of children and adolescents in clinical trials is the clear priority and all efforts should be made to facilitate access to trials. However, currently there are children who receive innovative medicines outside clinical trials and the related data are not captured [48,49]. Furthermore, these data should be made available for prescribers and families and useable for regulatory purposes.…”

Section: Real World Evidence (Rwe)mentioning

confidence: 99%

ACCELERATE – Five years accelerating cancer drug development for children and adolescents

Pearson¹,

Weiner²,

Adamson

et al. 2022

European Journal of Cancer

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Section: Real World Evidence (Rwe)mentioning

confidence: 99%

ACCELERATE – Five years accelerating cancer drug development for children and adolescents

Pearson¹,

Weiner²,

Adamson

et al. 2022

European Journal of Cancer

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“…Similarly, in the United States, 11% of patients undergoing tumor profiling under the Veterans Affairs program received off‐label prescriptions for targeted therapies 19 . The increase in pediatric precision oncology 14 is illustrated by the 48.3% of requests reported in this work that were based on the presence of a specific molecular driver or molecular target.…”

Section: Discussionmentioning

confidence: 89%

Access to innovative therapies in pediatric oncology: Report of the nationwide experience in Canada

Judd,

Revon‐Riviere,

Grover

et al. 2024

Cancer Medicine

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BackgroundThe need for new therapies to improve survival and outcomes in pediatric oncology along with the lack of approval and accessible clinical trials has led to “out‐of‐trial” use of innovative therapies. We conducted a retrospective analysis of requests for innovative anticancer therapy in Canadian pediatric oncology tertiary centers for patients less than 30 years old between 2013 and 2020.MethodsInnovative therapies were defined as cancer‐directed drugs used (a) off‐label, (b) unlicensed drugs being used outside the context of a clinical trial, or (c) approved drugs with limited evidence in pediatrics. We excluded cytotoxic chemotherapy, cellular products, and cytokines.ResultsWe retrieved data on 352 innovative therapy drug requests. Underlying diagnosis was primary CNS tumor 31%; extracranial solid tumor 37%, leukemia/lymphoma 22%, LCH 2%, and plexiform neurofibroma 6%. RAS/MAP kinase pathway inhibitors were the most frequently requested innovative therapies in 28% of all requests followed by multi‐targeted tyrosine kinase inhibitors (17%), inhibitors of the PIK3CA‐mTOR‐AKT pathway (8%), immune checkpoints inhibitors (8%), and antibody drug conjugates (8%). In 112 out of 352 requests, innovative therapies were used in combination with another anticancer agent. 48% of requests were motivated by the presence of an actionable molecular target. Compassionate access accounted for 52% of all requests while public insurance was used in 27%. Mechanisms of funding varied between provinces.ConclusionThis real‐world data collection illustrates an increasing use of “out‐of‐trial” innovative therapies in pediatric oncology. This new field of practice warrants further studies to understand the impact on patient trajectory and equity in access to innovative therapies.

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“…Indeed, as most InMPs are studied on adults first, EAP might be particularly beneficial for pediatric populations, who might otherwise face substantial delays before treatments for life-threatening rare cancers and diseases become available. A retrospective analysis of all single patient IND applications from a single pediatric oncology institution over a 2-year period reported that the FDA approved all 171 submitted requests; lack of a pediatric clinical trial (65%) was the most common reason for EAP application ( 29 ).…”

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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Retrospective evaluation of single patient investigational new drug (IND) requests in pediatric oncology

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 8 publications

References 20 publications

ACCELERATE – Five years accelerating cancer drug development for children and adolescents

ACCELERATE – Five years accelerating cancer drug development for children and adolescents

Access to innovative therapies in pediatric oncology: Report of the nationwide experience in Canada

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

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