Dataset Information

Real World-Evidence for Regulatory Use Decision Aid: An Interactive Tool To Inform Clinical Development and Regulatory Strategies.

ABSTRACT: Real-world evidence (RWE) is increasingly used to complement clinical trial data for regulatory decision-making and in certain cases utilized to establish the clinical effectiveness of a therapy. However, the use of RWE is not applicable for all regulatory submissions, and it can be challenging to identify appropriate use cases. An interactive tool was developed ("Decision Aid," https://sn.pub/TpDjZx ) to assist researchers, industry, and other stakeholders in identifying regulatory situations that can benefit from leveraging RWE by organizing precedent cases based on a given regulatory objective (new product approval, labeling expansion for new indication or additional clinical data, post-marketing requirement) and type of RWE study design (external control, observational study, pragmatic trial). Key success factors ensuring fit-for-purpose data and rigorous methods (e.g., clear endpoints, minimizing bias, data completeness) are also described. The tool allows the user to navigate through the precedent cases by selecting certain regulatory objectives and/or study designs. The Decision Aid supports regulatory activities in the RWE space and encourages further use of RWE in regulatory decision-making.

SUBMITTER: Burns L

PROVIDER: S-EPMC9379219 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Real World-Evidence for Regulatory Use Decision Aid: An Interactive Tool To Inform Clinical Development and Regulatory Strategies.

Burns Leah L Kalesnik-Orszulak Robert R Spring Rick R Zeegers Fabienne F Rutstein Mark M Hukkelhoven Mathias M Wruck Lisa L O'Donnell John J

Advances in therapy 20220816 10

Real-world evidence (RWE) is increasingly used to complement clinical trial data for regulatory decision-making and in certain cases utilized to establish the clinical effectiveness of a therapy. However, the use of RWE is not applicable for all regulatory submissions, and it can be challenging to identify appropriate use cases. An interactive tool was developed ("Decision Aid," https://sn.pub/TpDjZx ) to assist researchers, industry, and other stakeholders in identifying regulatory situations t ...[more]

PMID: 35972721

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Project description:BACKGROUND:Humanitarian action in crisis zones is fraught with many challenges, including lack of timely and accessible research evidence to inform decision-making about humanitarian interventions. Evidence websites have the potential to address this challenge. Evidence Aid is the only evidence website designed for crisis zones that focuses on providing research evidence in the form of systematic reviews. The objective of this study is to explore stakeholders' views of Evidence Aid, contributing further to our understanding of the use of research evidence in decision-making in crisis zones. METHODS:We designed a qualitative user-testing study to collect interview data from stakeholders about their impressions of Evidence Aid. Eligible stakeholders included those with and without previous experience of Evidence Aid. All participants were either currently working or have worked within the last year in a crisis zone. Participants were asked to perform the same user experience-related tasks and answer questions about this experience and their knowledge needs. Data were analysed using a deductive framework analysis approach drawing on Morville's seven facets of the user experience - findability, usability, usefulness, desirability, accessibility, credibility and value. RESULTS:A total of 31 interviews were completed with senior decision-makers (n?=?8), advisors (n?=?7), field managers (n?=?7), analysts/researchers (n?=?5) and healthcare providers (n?=?4). Participant self-reported knowledge needs varied depending on their role. Overall, participants did not identify any 'major' problems (highest order) and identified only two 'big' problems (second highest order) with using the Evidence Aid website, namely the lack of a search engine on the home page and that some full-text articles linked to/from the site require a payment. Participants identified seven specific suggestions about how to improve Evidence Aid, many of which can also be applied to other evidence websites. CONCLUSIONS:Stakeholders in crisis zones found Evidence Aid to be useful, accessible and credible. However, they experienced some problems with the lack of a search engine on the home page and the requirement for payment for some full-text articles linked to/from the site.

Project description:IntroductionA review of European Union (EU)-funded initiatives linked to 'Real World Evidence' (RWE) was performed to determine whether their outputs could be used for the generation of real-world data able to support the European Medicines Agency (EMA)'s regulatory decision-making on medicines.MethodThe initiatives were identified from publicly available websites. Their topics were categorised into five areas: 'Data source', 'Methodology', 'Governance model', 'Analytical model' and 'Infrastructure'. To assess their immediate relevance for medicines evaluation, their therapeutic areas were compared with the products recommended for EU approval in 2016 and those included in the EMA pharmaceutical business pipeline.ResultsOf 171 originally identified EU-funded initiatives, 65 were selected based on their primary and secondary objectives (35 'Data source' initiatives, 15 'Methodology', 10 'Governance model', 17 'Analytical model' and 25 'Infrastructure'). These 65 initiatives received over 734 million Euros of public funding. At the time of evaluation, the published outputs of the 40 completed initiatives did not always match their original objectives. Overall, public information was limited, data access was not explicit and their sustainability was unclear. The topics matched 8 of 14 therapeutic areas of the products recommended for approval in 2016 and 8 of 15 therapeutic areas in the 2017-2019 pharmaceutical business pipeline. Haematology, gastroenterology or cardiovascular systems were poorly represented.ConclusionsThis landscape of EU-funded initiatives linked to RWE which started before 31 December 2016 highlighted that the immediate utilisation of their outputs to support regulatory decision-making is limited, often due to insufficient available information and to discrepancies between outputs and objectives. Furthermore, the restricted sustainability of the initiatives impacts on their downstream utility. Multiple projects focussing on the same therapeutic areas increase the likelihood of duplication of both efforts and resources. These issues contribute to gaps in generating RWE for medicines and diminish returns on the public funds invested.

Project description:Background: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is the first example of a learning health system in multiple sclerosis (MS). This paper describes the initial implementation of MS PATHS and initial patient characteristics. Methods: MS PATHS is an ongoing initiative conducted in 10 healthcare institutions in three countries, each contributing standardized information acquired during routine care. Institutional participation required the following: active MS patient census of ≥500, at least one Siemens 3T magnetic resonance imaging scanner, and willingness to standardize patient assessments, share standardized data for research, and offer universal enrolment to capture a representative sample. The eligible participants have diagnosis of MS, including clinically isolated syndrome, and consent for sharing pseudonymized data for research. MS PATHS incorporates a self-administered patient assessment tool, the Multiple Sclerosis Performance Test, to collect a structured history, patient-reported outcomes, and quantitative testing of cognition, vision, dexterity, and walking speed. Brain magnetic resonance imaging is acquired using standardized acquisition sequences on Siemens 3T scanners. Quantitative measures of brain volume and lesion load are obtained. Using a separate consent, the patients contribute DNA, RNA, and serum for future research. The clinicians retain complete autonomy in using MS PATHS data in patient care. A shared governance model ensures transparent data and sample access for research. Results: As of August 5, 2019, MS PATHS enrolment included participants (n = 16,568) with broad ranges of disease subtypes, duration, and severity. Overall, 14,643 (88.4%) participants contributed data at one or more time points. The average patient contributed 15.6 person-months of follow-up (95% CI: 15.5-15.8); overall, 166,158 person-months of follow-up have been accumulated. Those with relapsing-remitting MS demonstrated more demographic heterogeneity than the participants in six randomized phase 3 MS treatment trials. Across sites, a significant variation was observed in the follow-up frequency and the patterns of disease-modifying therapy use. Conclusions: Through digital health technology, it is feasible to collect standardized, quantitative, and interpretable data from each patient in busy MS practices, facilitating the merger of research and patient care. This approach holds promise for data-driven clinical decisions and accelerated systematic learning.

Project description:IntroductionTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation.MethodsTwo noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBM® MarketScan® Commercial and Medicare Supplemental US insurance claims databases (March 2016-October 2018). Second, using data collected in the Corrona US RA Registry (February 2016-August 2019), two Clinical Disease Activity Index (CDAI)-based measures of effectiveness were compared between tofacitinib MR 11 mg QD and IR 5 mg BID, and against noninferiority criteria derived from placebo-controlled clinical trials of the tofacitinib IR formulation. Multiple sensitivity analyses of the registry data were conducted to reassure regulators of consistent results across different assumptions.ResultsIn each study, approximately two-thirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority of tofacitinib MR vs IR was demonstrated for both CDAI outcomes at ~6 months; this finding was robust across multiple sensitivity analyses.ConclusionThese results demonstrate the value of real-world evidence from complementary data sources in understanding the impact of medication adherence with a QD formulation in clinical practice. These analyses were suitable for regulatory consideration as an important component of evidence for the comparability of tofacitinib MR 11 mg QD vs IR 5 mg BID in patients with RA.Trial registrationClaims database study: ClinicalTrials.gov identifier NCT04018001, retrospectively registered July 12, 2019. Corrona US RA Registry study: ClinicalTrials.gov identifier NCT04267380, retrospectively registered February 12, 2020.

Dataset Information

Real World-Evidence for Regulatory Use Decision Aid: An Interactive Tool To Inform Clinical Development and Regulatory Strategies.

Publications

Real World-Evidence for Regulatory Use Decision Aid: An Interactive Tool To Inform Clinical Development and Regulatory Strategies.

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