Effective Data Sharing as a Conduit for Advancing Medical Product Development

Karpen, Stephen R.; White, Jensen Kael; Mullin, Ariana P.; O’Doherty, Inish; Hudson, Lynn D.; Romero, Klaus; Sivakumaran, Sudhir; Stephenson, Diane; Turner, Emily C.; Larkindale, Jane

doi:10.1007/s43441-020-00255-8

Cited by 22 publications

(15 citation statements)

References 20 publications

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“…The importance of an in-depth description of patient characteristics is equally relevant for observational and interventional trial data to address confounding factors and bias (European Medicines Agency, 2021). Patients are characterized in the greatest depth in clinical trials, but much of this information may be lost for the purpose of a scientific publication (Karpen et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…A wide spectrum of data sources (or study designs) is collectively referred to as representing the real world from purely administrative to prospective observational research (Makady et al, 2017). These types of data strongly differ with respect to the depth of clinical information that is collected, and, depending on the reporting format, provided for assessment (Karpen et al, 2021). Administrative data are restricted to diagnostic codes that-by a combination of codes and their chronological order-may be used to describe the (long-term) consequences of specific treatment patterns.…”

Section: Introductionmentioning

confidence: 99%

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Licensing of Orphan Medicinal Products—Use of Real-World Data and Other External Data on Efficacy Aspects in Marketing Authorization Applications Concluded at the European Medicines Agency Between 2019 and 2021

et al. 2022

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Background: Reference to so-called real-world data is more often made in marketing authorization applications for medicines intended to diagnose, prevent or treat rare diseases compared to more common diseases. We provide granularity on the type and aim of any external data on efficacy aspects from both real-world data sources and external trial data as discussed in regulatory submissions of orphan designated medicinal products in the EU. By quantifying the contribution of external data according to various regulatory characteristics, we aimed at identifying specific opportunities for external data in the field of orphan conditions.Methods: Information on external data in regulatory documents covering 72 orphan designations was extracted. Our sample comprised public assessment reports for approved, refused, or withdrawn applications concluded from 2019–2021 at the European Medicines Agency. Products with an active orphan designation at the time of submission were scrutinized regarding the role of external data on efficacy aspects in the context of marketing authorization applications, or on the criterion of “significant benefit” for the confirmation of the orphan designation at the time of licensing. The reports allowed a broad distinction between clinical development, regulatory decision making, and intended post-approval data collection. We defined three categories of external data, administrative data, structured clinical data, and external trial data (from clinical trials not sponsored by the applicant), and noted whether external data concerned the therapeutic context of the disease or the product under review.Results: While reference to external data with respect to efficacy aspects was included in 63% of the approved medicinal products in the field of rare diseases, 37% of marketing authorization applications were exclusively based on the dedicated clinical development plan for the product under review. Purely administrative data did not play any role in our sample of reports, but clinical data collected in a structured manner (from routine care or clinical research) were often used to inform on the trial design. Two additional recurrent themes for the use of external data were the contextualization of results, especially to confirm the orphan designation at the time of licensing, and reassurance of a large difference in treatment effect size or consistency of effects observed in clinical trials and practice. External data on the product under review were restricted to either active substances already belonging to the standard of care even before authorization or to compassionate use schemes. Furthermore, external data were considered pivotal for marketing authorization only exceptionally and only for active substances already in use within the specific therapeutic indication. Applications for the rarest conditions and those without authorized treatment alternatives were especially prominent with respect to the use of external data from real-world data sources both in the pre- and post-approval setting.Conclusion: Specific opportunities for external data in the setting of marketing authorizations in the field of rare diseases were identified. Ongoing initiatives of fostering systematic data collection are promising steps for a more efficient medicinal product development in the field of rare diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Licensing of Orphan Medicinal Products—Use of Real-World Data and Other External Data on Efficacy Aspects in Marketing Authorization Applications Concluded at the European Medicines Agency Between 2019 and 2021

et al. 2022

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“…Currently, attempts are being made for regulatory qualification of islet autoantibodies as enrichment biomarkers for use in T1D prevention clinical trials (27). Once the initiation of AID has been clarified, the prediction would be that other diagnostic criteria and treatment approaches will be worked out and become available.…”

Section: Etiology Of Aidmentioning

confidence: 99%

Etiology of Autoimmune Islet Disease: Timing Is Everything

Lernmark

2021

Diabetes

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Life is about timing. —Carl Lewis The understanding of autoimmune type 1 diabetes is increasing, and examining etiology separate from pathogenesis has become crucial. The components to explain type 1 diabetes development have been known for some time. The strong association with HLA has been researched for nearly 50 years. Genome-wide association studies added another 60+ non-HLA genetic factors with minor contribution to risk. Insulitis has long been known to be present close to clinical diagnosis. T and B cells recognizing β-cell autoantigens are detectable prior to diagnosis and in newly diagnosed patients. Islet autoantibody tests against four major autoantigens have been standardized and used as biomarkers of islet autoimmunity. However, to clarify the etiology would require attention to time. Etiology may be defined as the cause of a disease (i.e., type 1 diabetes) or abnormal condition (i.e., islet autoimmunity). Timing is everything, as neither the prodrome of islet autoimmunity nor the clinical onset of type 1 diabetes tells us much about the etiology. Rather, the islet autoantibody that appears first and persists would mark the diagnosis of an autoimmune islet disease (AID). Events after the diagnosis of AID would represent the pathogenesis. Several islet autoantibodies without (stage 1) or with impaired glucose tolerance (stage 2) or with symptoms (stage 3) would define the pathogenesis culminating in clinical type 1 diabetes. Etiology would be about the timing of events that take place before the first-appearing islet autoantibody.

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“…We propose that interventional clinical trials and observational studies be planned and consented with open science practices in mind (Table 4) (21). For example, the publicly available ADNI data have been extremely useful in advancing AD research and planning clinical trials (22)(23)(24), and the HD research community is now providing access to harmonized observational datasets from studies such as Enroll-HD, IMAGE-HD, PREDICT-HD, and TRACK-HD.…”

Section: Broad Sharing Of Imaging Data From Interventional Trials and Observational Studiesmentioning

confidence: 99%

“…Participant-level data, including images, should be made available through a neutral party; this will require participant identity protection that complies with GDPR as well as the Health Insurance Portability and Accountability Act (HIPAA). C-Path has previously published recommendations for effective sharing of participant-level data to advance medical product development while maintaining data security and patient privacy (21). Image data should be provided in a standard neuroimaging format that includes all the acquisition parameters necessary for image processing.…”

Section: Broad Sharing Of Imaging Data From Interventional Trials and Observational Studiesmentioning

confidence: 99%

Recommendations to Optimize the Use of Volumetric MRI in Huntington's Disease Clinical Trials

et al. 2021

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Volumetric magnetic resonance imaging (vMRI) has been widely studied in Huntington's disease (HD) and is commonly used to assess treatment effects on brain atrophy in interventional trials. Global and regional trajectories of brain atrophy in HD, with early involvement of striatal regions, are becoming increasingly understood. However, there remains heterogeneity in the methods used and a lack of widely-accessible multisite, longitudinal, normative datasets in HD. Consensus for standardized practices for data acquisition, analysis, sharing, and reporting will strengthen the interpretation of vMRI results and facilitate their adoption as part of a pathobiological disease staging system. The Huntington's Disease Regulatory Science Consortium (HD-RSC) currently comprises 37 member organizations and is dedicated to building a regulatory science strategy to expedite the approval of HD therapeutics. Here, we propose four recommendations to address vMRI standardization in HD research: (1) a checklist of standardized practices for the use of vMRI in clinical research and for reporting results; (2) targeted research projects to evaluate advanced vMRI methodologies in HD; (3) the definition of standard MRI-based anatomical boundaries for key brain structures in HD, plus the creation of a standard reference dataset to benchmark vMRI data analysis methods; and (4) broad access to raw images and derived data from both observational studies and interventional trials, coded to protect participant identity. In concert, these recommendations will enable a better understanding of disease progression and increase confidence in the use of vMRI for drug development.

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Effective Data Sharing as a Conduit for Advancing Medical Product Development

Cited by 22 publications

References 20 publications

Licensing of Orphan Medicinal Products—Use of Real-World Data and Other External Data on Efficacy Aspects in Marketing Authorization Applications Concluded at the European Medicines Agency Between 2019 and 2021

Licensing of Orphan Medicinal Products—Use of Real-World Data and Other External Data on Efficacy Aspects in Marketing Authorization Applications Concluded at the European Medicines Agency Between 2019 and 2021

Etiology of Autoimmune Islet Disease: Timing Is Everything

Recommendations to Optimize the Use of Volumetric MRI in Huntington's Disease Clinical Trials

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