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Quantifying Patient Investment in Novel Neurological Drug Development


While the drug development literature provides numerous estimates of the financial costs to bring a new drug to market, the investment of patient-participants in the research process has not been described. Trial participants and their caregivers, like companies, invest time and undertake risk when they participate in prelicense trials. We determined the average number of patient-participants needed to develop a novel neurological drug. We created a cohort of 108 unapproved drugs first tested for efficacy between 2006 and 2011 and used to capture enrollment in all subsequent prelicense trials of these drugs over a 9-year period. Our primary outcome was the average number of patients enrolled in prelicense neurological drug trials per drug that ultimately attained FDA approval, including patients who participated in both successful and unsuccessful development efforts. Five drugs (4.6%) were FDA approved, and 66,751 patient-participants were enrolled across successful and unsuccessful drug development efforts, resulting in an average of 13,350 patients for each drug attaining approval (95% CI 7155 to 54,954). Our estimates reveal the substantial amount patients and their caregivers contribute to private drug development.

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  1. Wouters OJ, McKee M, Luyten J. Estimated research and development investment needed to bring a new medicine to market, 2009–2018. JAMA. 2020;323:844–53.

    Article  Google Scholar 

  2. DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20–33.

    Article  Google Scholar 

  3. Karlawish J, Cary M, Moelter ST, Siderowf A, Sullo E, Xie S, et al. Cognitive impairment and PD patients’ capacity to consent to research. Neurology. 2013;81:801–7.

    Article  Google Scholar 

  4. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med. 1987;317:141–5.

    CAS  Article  Google Scholar 

  5. Feustel AC, MacPherson A, Fergusson DA, Kieburtz K, Kimmelman J. Risks and benefits of unapproved disease-modifying treatments for neurodegenerative disease. Neurology. 2020;94:e1-14.

    CAS  Article  Google Scholar 

  6. Carlisle B, Demko N, Freeman G, Hakala A, MacKinnon N, Ramsay T, et al. Benefit, risk, and outcomes in drug development: a systematic review of sunitinib. J Natl Cancer Inst. 2016;108:djv292.

  7. Carlisle BG, Zheng T, Kimmelman J. Imatinib and the long tail of targeted drug development. Nat Rev Clin Oncol. 2020;17:1–3.

    Article  Google Scholar 

  8. Hutchinson N, Carlisle B, Doussau A, Bosan R, Gumnit E, MacPherson A, et al. Patient participation in clinical trials of oncology drugs and biologics preceding approval by the US Food and Drug Administration. JAMA Netw Open. 2021;4: e2110456.

    Article  Google Scholar 

  9. Duijnhoven RG, Straus SMJM, Raine JM, de Boer A, Hoes AW, De Bruin ML. Number of patients studied prior to approval of new medicines: a database analysis. PLoS Med. 2013;10: e1001407.

    Article  Google Scholar 

  10. London AJ, Kimmelman J. Why clinical translation cannot succeed without failure. eLife. 2015;4:e12844.

  11. Choi DW, Armitage R, Brady LS, Coetzee T, Fisher W, Hyman S, et al. Medicines for the mind: policy-based “pull” incentives for creating breakthrough CNS drugs. Neuron. 2014;84:554–63.

    CAS  Article  Google Scholar 

  12. Grill JD, Karlawish J. Addressing the challenges to successful recruitment and retention in Alzheimer’s disease clinical trials. Alzheimers Res Ther. 2010;2:34.

    CAS  Article  Google Scholar 

  13. Zarin DA, Goodman SN, Kimmelman J. Harms from uninformative clinical trials. JAMA. 2019;322:813–4.

    Article  Google Scholar 

  14. Paganoni S, Berry JD, Quintana M, Macklin E, Saville BR, Detry MA, et al. Adaptive platform trials to transform amyotrophic lateral sclerosis therapy development. Ann Neurol. 2022;91:165–75.

    Article  Google Scholar 

  15. Li V, Leurent B, Barkhof F, Braisher M, Cafferty F, Ciccarelli O, et al. Designing multi-arm multistage adaptive trials for neuroprotection in progressive multiple sclerosis. Neurology. 2022;98:754-764.

    Article  PubMed  PubMed Central  Google Scholar 

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This project was supported by CIHR. We thank the anonymous referees for their review and input.

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Conception and design of the study: JK, NH, and AM. Acquisition and analysis of the data: AM, EG, CO, KK, and TSP. Drafting of the manuscript: AM and JK.

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Correspondence to Jonathan Kimmelman.

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JK reports receiving consulting fees from Amylyx Pharmaceuticals. The authors otherwise declare no competing interests.

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MacPherson, A., Gumnit, E., Ouimet, C. et al. Quantifying Patient Investment in Novel Neurological Drug Development. Neurotherapeutics (2022).

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  • Drug development
  • Clinical trials
  • Research ethics
  • CNS disorders