Real world evidence studies: how to develop and implement the new direction. Systematic approach for assuring the quality of results

Khomitskaya Yu.V.; Osina G.S.; Goldina T.A.

doi:https://doi.org/10.17116/medtech20214304116

Close metadata

Abstract:

The evidence obtained in clinical trials (CTs) and real world evidence (RWE) studies represents a joint evidence base for health technology assessment and decision-making in healthcare. The key factors for RWE acceptance by the regulatory authorities and health technology assessment agencies are quality of original data and proper methods for processing of these data. The lack of a unified regulatory framework for planning and conducting the RWE studies significantly complicates this objective. This manuscript is devoted to systematic approach to development and implementation of RWE direction in a company. This approach is aimed at ensuring the quality of results. The authors describe all the key components necessary for development and implementation of RWE direction in a company: strategy, analysis of internal and external environment, quality management system (QMS), partnership model and processes for development and implementation of RWE studies. The main actions and objectives for each stage of RWE are formulated. Relationship of each stage with ensuring the quality of RWE study results is shown. The key internal processes and minimum necessary requirements for each of processes has been described for the first time in the Russian-language scientific literature. The described systematic principles can be leveraged to implement an innovation not only in pharmaceutical companies or contract research organizations, but also in partner companies providing access to data and/or information technologies, healthcare organizations and research institutes. Implementation of principles, requirements, methods and algorithms significantly contribute to establishment of RWE direction in companies and form a systematic approach to ensuring the quality of RWE studies results.

Keywords:

real world data (RWD)

real world study (RWS)

real world evidence (RWE)

study processes

quality management system (QMS)

Authors:

Khomitskaya Yu.V.

«Servier» JSC

Osina G.S.

«Roche — Moscow» JSC

Goldina T.A.

Sanofi Russia

Scopus AuthorID: 57370889200
ORCID: 0000-0002-2680-7035

Received:

27.08.2021

Accepted:

21.09.2021

Close metadata

References:

21st Century Cures Act PUBLIC LAW 114-255. An Act to accelerate the discovery, development, and delivery of 21st century cures, and for other purposes (21st Century Cures Act). 2016. Accessed August 18, 2021. https://www.congress.gov/114/plaws/publ255/PLAW-114publ255.pdf
Goldina TA, Burmistrov VA, Efimenko IV, Khoroshevskiy VF. Artificial Intelligence in Healthcare: Real World Data and Patient Voice — Are We Ready for New Realities? Medicinskie tekhnologii. Ocenka i vybor. 2021;43(2):22-31. (In Russ.). https://doi.org/10.17116/medtech20214302122
Goldina TA, Suvorov NI. Real-World Data Studies: from Data to Health Technology Assessment and Decision-Making in Healthcare. Medicinskie tekhnologii. Ocenka i vybor. 2018;31(1):21-29. (In Russ.).
Solodovnikov AG, Sorokina EYu, Goldina TA. Real-world data: from planning to analysis. Medicinskie Tekhnologii. Ocenka i Vybor. 2020;41(3):9-16. (In Russ.). https://doi.org/10.17116/medtech2020410316
Issledovaniya real’noj klinicheskoj praktiki. Pod red. Kolbina A.S. M.: Izdatel’stvo OKI: Buki Vedi; 2020. Accessed August 18, 2021. (In Russ.). https://clck.ru/QkeeP
Rotwell PM. External validity of randomised controlled trials: «To whom do the results of this trial apply?» Lancet. 2005;365(9453):82-93. https://doi.org/10.1016/S0140-6736(04)17670-8
U.S. Food and Drug Administration. Framework for FDA’s Real-World Evidence program. December, 2018. Accessed August 24, 2021. https://www.fda.gov/media/120060/download
U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drugs and Biologics. Guidance for Industry. FDA-2019-D-1263. May 2019. Accessed August 24, 2021. https://www.fda.gov/media/124795/download
Eichler HG, Pignatti F, Schwarzer-Daum B, Hidalgo-Simon A, Eichler I, Arlett P, et al. Randomized Controlled Trials Versus Real World Evidence: Neither Magic Nor Myth. Clinical Pharmacology and Therapeutics. 2021;109(5):1212-1218. https://doi.org/10.1002%2Fcpt.2083
Honig PK. Real-World Evidence and the Regulation of Medicines. Clinical Pharmacology and Therapeutics. 2021;109(5):1169-1172. https://doi.org/10.1002/cpt.2230
Sourcing Real World Data. Understanding diverse real world data sources and the questions, they can answer. IQVIA Insights Guide. January, 19, 2021. Accessed August 18, 2021. https://www.iqvia.com/library/white-papers/sourcing-real-world-data
Selecting Real World Data. A guide to selecting the right real world data to support your research. IQVIA Insights Guide. January, 19, 2021. Accessed August 18, 2021. https://www.iqvia.com/library/white-papers/selecting-real-world-data
IQWiG Reports — Commission No. A19-43. Concepts for the generation of routine practice data and their analysis for the benefit assessment of drugs according to § 35a Social Code Book V. January 10, 2020. Accessed August 24, 2021. https://www.iqwig.de/en/projects/a19-43.html
Franklin JM, Glynn RJ, Martin D, Schneeweis S. Evaluating the Use of Nonrandomized Real-World Data Analyses for Regulatory Decision Making. Clinical Pharmacology and Therapeutics. 2019;105(4):867-877. https://doi.org/10.1002/cpt.1351
Cox E, Martin BC, Van Staa T, Garbe E, Siebert U, Johnson ML. Good research practices for comparative effectiveness research: Approaches to mitigate bias and confounding in the design of nonrandomized studies of treatment effects using secondary data sources: The International Society for Pharmacoeconomics and Outcomes Research Good Research Practices for Retrospective Database Analysis Task Force Report — Part II. Value in Health. 2009;12(8):1053-1061. https://doi.org/10.1111/j.1524-4733.2009.00601.x
Elements of real world data/evidence quality throughout the prescription drug product life cycle. March 5, 2019. Accessed July 19.2021. https://www.canada.ca/en/services/health/publications/drugs-health-products/real-world-data-evidence-drug-lifecycle-report.html
U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Best Practices for Conducting and Reporting Pharmacoepidemiologic Safety Studies Using Electronic Healthcare Data Sets. FDA-2011-D-0057. May 2013. Accessed July 19, 2021. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/best-practices-conducting-and-reporting-pharmacoepidemiologic-safety-studies-using-electronic
Berger ML, Sox H, Willke RJ, Brixner DL, Eichler HG, Goettsch W, et al. Good Practices for Real-World Data Studies of Treatment and/or Comparative Effectiveness: Recommendations from the Joint ISPOR‐ISPE Special Task Force on Real-World Evidence in Health Care Decision Making. Value in Health. 2017;20(8):1003-1008. https://doi.org/10.1016/j.jval.2017.08.3019
Patient-Centered Outcomes Research Institute (PCORI) Methodology Committee. The PCORI Methodology Report. January 2019. Accessed August 25, 2021. www.pcori.org/methodology-standards
HMA-EMA Joint Big Data Taskforce Phase II report: Evolving Data-Driven Regulation. EMA/584203/2019. 2019. Accessed August 25, 2021. https://www.ema.europa.eu/en/documents/other/hma-ema-joint-big-data-taskforce-phase-ii-report-evolving-data-driven-regulation_en.pdf
U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Use of Electronic Health Record Data in Clinical Investigations Guidance for Industry FDA-2016-D-1224. July 2018. Accessed August 25, 2021. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-electronic-health-record-data-clinical-investigations-guidance-industry
Orsini LS, Berger M, Crown W, Daniel G, Eichler HG, Goettsch W, et al. Improving Transparency to Build Trust in Real-World Secondary Data Studies for Hypothesis Testing — Why, What, and How: Recommendations and a Road Map from the Real-World Evidence Transparency Initiative. Value in Health. 2020;23(9):1128-1136. https://doi.org/10.1016/j.jval.2020.04.002
Johnson M, Crown W, Martin B, Dormuth C, Siebert U. Good research practices for comparative effectiveness research: analytic methods to improve causal inference from nonrandomized studies of treatment effects using secondary data sources: the ISPOR Good Research Practices for Retrospective Database Analysis Task Force Report — Part III. Value in Health. 2009;12(8):1062-1073. https://doi.org/10.1111/j.1524-4733.2009.00602.x
Wang SV, Schneeweiss S, Berger ML, Brown J, de Vries F, Douglas I, et al.; joint ISPE‐ISPOR Special Task Force on Real World Evidence in Health Care Decision Making. Reporting to Improve Reproducibility and Facilitate Validity Assessment for Healthcare Database Studies V1.0. Value in Health. 2017;20(8):1009-1022. https://doi.org/10.1016/j.jval.2017.08.3018
Berger ML, Martin BC, Husereau D, Worley K, Allen JD, Yang W, et al. A questionnaire to assess the relevance and credibility of observational studies to inform health care decision making: an ISPOR-AMCP-NPC Good Practice Task Force report. Value in Health. 2014;17(2):143-156. https://doi.org/10.1016/j.jval.2013.12.011
Franklin JM, Liaw K-L, Iyasu S, Critchlow C, Dreyer N. Real-world evidence to support regulatory decision making: New or expanded medical product indications. Pharmacoepidemiology and Drug Safety. 2021;30(6):685-693. https://doi.org/10.1002/pds.5222
Empfehlungen des Bundesinstituts fur Arzneimittel und Medizinprodukte und des Paul-Ehrlich-Instituts zur Planung, Durchfuhrung und Auswertung von Anwendungsbeobachtungen (AWB) vom 7. Juli 2010. Accessed July 14, 2021. https://www.pei.de/DE/regulation/klinische-pruefung/anwendungsbeobachtungen/awb-node.html
Kodeks nadlezhashchej praktiki Associacii mezhdunarodnyh farmacevticheskih proizvoditelej 2019. Accessed July 14, 2021. https://www.ifpma.org/wp-content/uploads/2020/09/AIPM-Code-of-Practice-2019.pdf
Hulley S, Cummings S, Browner W, Grady DG, Newman TB. Designing clinical research. 3rd ed. Philadelphia (PA): Lippincott Williams and Wilkins; 2007.
Fandino W. Formulating a good research question: Pearls and pitfalls. Indian Journal of Anaesthesia. 2019;63(8):611-616. https://doi.org/10.4103/ija.IJA_198_19
Khomitskaya Y, Shulepina E, Korovkina N, Trifonova O, Saburkina N, Grishin A, et al. A descriptive analysis of patient characteristics from Russian internet postings focused on CRC (iPatient study). Annals of Oncology. 2020;31(suppl S3):93. https://doi.org/10.1016/j.annonc.2020.04.094
Battisti WP, Wager E, Baltzer L, Bridges D, Cairns A, Carswell CI, et al.; International Society for Medical Publication Professionals. Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3. Annals of Internal Medicine. 2015;163(6):461-464. https://doi.org/10.7326/M15-0288
Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals. Accessed July 14, 2021. https://www.icmje.org/icmje-recommendations.pdf
Pravila nadlezhashchej klinicheskoj praktiki Evrazijskogo ekonomicheskogo soyuza ot 03.11.2016 №79. Accessed July 14, 2021. (In Russ.). https://docs.cntd.ru/document/456026110
Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ. 2007;335:806. https://doi.org/10.1136/bmj.39335.541782.AD
Edwards LD, Fox AW, Stonier PD, eds. Principles and Practice of Pharmaceutical Medicine. 3d ed. Wiley; 2011.