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Reproducibility of real-world evidence studies using clinical practice data to inform regulatory and coverage decisions.

ABSTRACT: Studies that generate real-world evidence on the effects of medical products through analysis of digital data collected in clinical practice provide key insights for regulators, payers, and other healthcare decision-makers. Ensuring reproducibility of such findings is fundamental to effective evidence-based decision-making. We reproduce results for 150 studies published in peer-reviewed journals using the same healthcare databases as original investigators and evaluate the completeness of reporting for 250. Original and reproduction effect sizes were positively correlated (Pearson's correlation = 0.85), a strong relationship with some room for improvement. The median and interquartile range for the relative magnitude of effect (e.g., hazard ratio_original/hazard ratio_reproduction) is 1.0 [0.9, 1.1], range [0.3, 2.1]. While the majority of results are closely reproduced, a subset are not. The latter can be explained by incomplete reporting and updated data. Greater methodological transparency aligned with new guidance may further improve reproducibility and validity assessment, thus facilitating evidence-based decision-making. Study registration number: EUPAS19636.

SUBMITTER: Wang SV

PROVIDER: S-EPMC9430007 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Reproducibility of real-world evidence studies using clinical practice data to inform regulatory and coverage decisions.

Wang Shirley V SV Sreedhara Sushama Kattinakere SK Schneeweiss Sebastian S

Nature communications 20220831 1

Studies that generate real-world evidence on the effects of medical products through analysis of digital data collected in clinical practice provide key insights for regulators, payers, and other healthcare decision-makers. Ensuring reproducibility of such findings is fundamental to effective evidence-based decision-making. We reproduce results for 150 studies published in peer-reviewed journals using the same healthcare databases as original investigators and evaluate the completeness of report ...[more]

PMID: 36045130

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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.

Project description:Background: Despite the ongoing innovations and the availability of numerous effective inhaled treatment options, achieving optimal disease control in most patients frequently remains disappointing. Unfortunately, although inhaled therapy is the cornerstone of respiratory disease management, the selection of the most appropriate inhaler is still overlooked or underestimated by some healthcare professionals, and inhaler misuse remains a significant challenge in managing chronic respiratory diseases which directly influences patients' quality of life, clinical outcomes, and risk of disease progression. Materials and Methods: This is a unicentric, observational, cross-sectional study designed to evaluate the inhaled therapy prescribed in hospitalized patients and to analyze device changes after hospitalization, as well as the factors associated with these changes. A single face-to-face visit was performed during the patient's hospitalization, where the inhaled therapy used prior to hospitalization was evaluated: technique (critical errors), compliance (TAI questionnaire), maximum peak inspiratory flow [PIF (L/min)], and level of inhaler handling-related knowledge. A binary logistic regression model was used to explore the association between changing device at discharge and the other independent variables Results: The inhaler most used during hospitalization was the metered-dose inhaler (MDI) with a chamber (51.9% of patients), with the dry powdered inhalers (DPI) being the inhalers used in 43% of maintenance inhaled therapies in the community setting prior to hospitalization. In addition, 90% of patients showed a maximum PIF ≥ 30 L/min, and 35.6% performed critical inhaler errors. These patients had statistically significantly lower maximum PIF values (52.1 L/min in patients with critical inhaler errors vs. 60.8 L/min without critical inhaler errors; p > 0.001) and were more likely to exhibit poor inhaler compliance compared to those without critical errors (50.5% vs. 31.0%, respectively). More than half of the patients who used MDI with spacer chamber made critical inhaler errors; 69.9% showed regular or poor treatment adherence, although 75.6% demonstrated good knowledge about inhaler handling. Only in 27% of the patients did the healthcare professional change the type of inhaler after hospitalization within clinical practice. The medical and nursing staff responsible for the patient's hospitalization were not informed of the assessment carried out in the study. The probability of not performing a device change at discharge was lower in patients with previous at-home treatment with combined inhaled therapy with LABA + ICS (OR 0.3 [0.18-0.83], p = 0.016) and in patients under triple inhaled therapy (OR 0.3 [0.17-0.76], p = 0.007). No significant differences were observed in inhaler changes when considering the frequency of critical inhaler errors, inhaler handling-related knowledge or maximum PIF values. Conclusions: Our study highlights the urgent need for a more personalized inhaler selection and consistent monitoring by healthcare professionals to minimize inhaler misuse, increase treatment compliance and adherence, and improve disease management outcomes. It is essential to provide training and promote the role of nursing in the evaluation and education of inhaled therapy. Additionally, the use of standardized approaches and tools, such as the CHECK DIAL, is crucial to facilitate the adaptation of devices to patients' needs.

Dataset Information

Reproducibility of real-world evidence studies using clinical practice data to inform regulatory and coverage decisions.

Publications

Reproducibility of real-world evidence studies using clinical practice data to inform regulatory and coverage decisions.

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