Calibration of the influence of external factors — country, city (infrastructure), and income on patient recruitment in clinical trials

   Relevance. The number of international multicenter clinical trials and patient recruitment varies across countries, influenced by a variety of external factors such as the availability of experienced research centers, a sufficient patient pool, convenient logistics, the presence of competing studies, cost, political situation in the country, the timing of clinical trial approval by the regulator and ethics committee, the availability of a regulatory framework for clinical trials harmonized with ICH GCP, etc. At the same time, the speed of patient recruitment, along with the quality of data, remains one of the leading reasons for changes in the number of clinical trials in countries around the world. Clinical trials are usually conducted in cities where there is the necessary equipment to conduct the protocol, and the patient can get to the clinical center without special efforts. The authors emphasize that living close to a clinical center increases the motivation of patients to participate in a clinical trial. Many authors have also studied the relationship between patient recruitment and income.

   Objective. Calculate the quantitative impact of country, city (infrastructure), and income on patient recruitment.

   Materials and methods. The data were obtained for a period of 13 years from July 2008 to July 2021 during 4 international multicenter clinical trials of phases II–III. A retrospective analysis was conducted on the recruitment of patients depending on the influence of various factors — country, city (infrastructure) and income. Using the odds ratio method, a quantitative calibration of the influence of the selected factors was carried out.

   Conclusions. For the first time, the impact of external factors on patient recruitment in clinical studies was calibrated — country, city (infrastructure) and income. It was shown that the country, as an external factor, has a medium and weak impact on patient recruitment. Residence in the cities of Moscow, St. Petersburg and Kyiv has almost the same impact on patient recruitment as the country of residence. Clinical centers located in locations with high incomes of the population, as a rule, are characterized by lower patient recruitment.

1. Friedman LM, Furberg CD, DeMets DL. Fundamentals of Clinical Trials. 4^th ed. New York: Springer; 2010. ISBN: 978-1-4419-1585-6. doi: 10.1007/978-1-4419-1586-3

2. Bachenheimer Joan F., Bonnie A. Brescia, Reinventing Patient Recruitment Revolutionary Ideas for Clinical Trial Success, Copyright Year 2007. 276 p.

3. Parke Jeff A. Clinical Trial Site Recruitment Guide. 2022. Available at: https://www.linkedin.com/feed/update/urn:li:activity:6956298942401642497. March 02, 2025.

4. Yen W. How long and how far do adults travel and will adults travel for primary care? Washington State Office of Financial Management; 2013. Research Brief No. 70. Available at: https://www.ofm.wa.gov/sites/default/files/public/legacy/researchbriefs/2013/brief070.pdf. Accessed February 24, 2025.

5. Blanch DC, Rudd RE, Wright E, et al. Predictors of refusal during a multi-step recruitment process for a randomized controlled trial of arthritis education. Patient Educ Couns. 2008 Nov;73(2):280-5. doi: 10.1016/j.pec.2008.06.017.

6. Schoenberger JA. Recruitment in the Coronary Drug Project and the Aspirin Myocardial Infarction Study. Clin Pharmacol Ther. 1979 May;25(5 Pt 2):681-4. doi: 10.1002/cpt1979255part2681.

7. Yang E, O'Donovan C, Phillips J, et al. Quantifying and visualizing site performance in clinical trials. Contemp Clin Trials Commun. 2018 Jan 31;9:108-114. doi: 10.1016/j.conctc.2018.01.005.

8. List of States and dependent territories by population. (In Russ.)] https://clck.ru/3GSpU7.

9. Cancer. Key facts. Available at: https://www.who.int/ru/news-room/factsheets/detail/cancer Accessed February 24, 2025.

10. Population of the world and countries. Available at: https://countrymeters.info/en Accessed February 24, 2025.

11. Melikyan AL, Pustovaya EI, Tsvetaeva NV. National clinical practice guidelines for the diagnosis and treatment of idiopathic thrombocytopenic purpura (primary immune thrombocytopenia) in adults (revised 2018). (In Russ.)] https://npngo.ru/uploads/media_document/283/5eb37419-9276-4e9a-b075-0e26a788f623.pdf.

12. Wild CP, Weiderpass E, Stewart BW, editors. World Cancer Report: Cancer research for cancer prevention. Lyon (FR): International Agency for Research on Cancer; 2020. PMID: 39432694. Available at: https://pubmed.ncbi.nlm.nih.gov/39432694/. Accessed February 24, 2025.

13. Ed by. AD Kaprin, VV Starinsky, AO Shakhzadova. Malignant neoplasms in Russia in 2020 (morbidity and mortality) Moscow: P. Hertsen Moscow Oncology Research Institute (MORI) - the branch of the FSBI «NMRRC» MOH Russia, 2021. (In Russ.) ISBN 978-5-85502-268-1.

14. Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019 Nov 26;3(22):3780-3817. doi: 10.1182/bloodadvances.2019000812.

15. The Global Liveability Report 2017. Available at: https://www.eiu.com/n/campaigns/the-global-liveability-report-2017-campaign-success. Accessed February 24, 2025.

16. Milovanov SS. Analysis of the rate of patient recruitment in international multi-center clinical studies. Questions of student science. 2019;33(5) part 1:20-26. (In Russ.) https://cyberleninka.ru/article/n/analiz-skorosti-nabora-patsientov-v-mezhdunarodnyh-multitsentrovyh-klinicheskih-issledovaniyah.

17. Global clinical trials market. (In Russ.) https://www.apteka.ua/article/158875

18. Kibby M. Patient recruitment feasibility. Applied Clinical Trials. 2011;20(6):80-87.

19. Kadam RA, Borde SU, Madas SA, et al. Challenges in recruitment and retention of clinical trial subjects. Perspect Clin Res. 2016 Jul-Sep;7(3):137-43. doi: 10.4103/2229-3485.184820.

20. Halpern SD, Karlawish JH, Casarett D, et al. Empirical assessment of whether moderate payments are undue or unjust inducements for participation in clinical trials. Arch Intern Med. 2004 Apr 12;164(7):801-3. doi: 10.1001/archinte.164.7.801.

21. Popov V.V., Saverskaya E.N., Bulanova N.A. Clinical trials of drugs: what a physician-researcher needs to know. Textbook for doctors - M: LARGO, 2023 - 206 p.

22. Milovanov S.S., Popov V.V., Bulanova N.A., Teplova N.V., Gratsianskaya A.N. Monitoring research centers during clinical trials : a training manual. Moscow: LARGO, 2024. – 72 p.