2023 / 01

Next Paper
DOI: 10.24075/medet.2023.006

REVIEW

Early phase clinical research as viewed by healthy volunteers

Fitilev SB, Vozzhaev AV, Shkrebniova II, Kliuev DA, Saakova LN
About authors

Рeoples’ Friendship University of Russia (RUDN University), Moscow, Russia

Correspondence should be addressed: Dmitry A. Kliuev
ul. Miklukho-Maclay, 6, Moscow, 117198, Russia; moc.liamg@694070veulkjirtimd

About paper

Author contribution: Fitilev SB — development of article concept, analysis of scientific data, article editing; Vozzhaev AV — development of article concept, analysis of scientific data, writing an article; Shkrebniova II — collection of data, analysis of scientific data, writing an article; Kliuev DA — review of the article-related publications, statistical calculations, writing an article; Saakova LN — collection of data, review of the article-related publications.

Compliance with ethical standards: voluntary informed consent was obtained from every participant. Questioning was conducted on a voluntary basis.

Received: 2023-02-02 Accepted: 2023-02-23 Published online: 2023-03-06
|
  1. Iltis AS. Payments to normal healthy volunteers in phase 1 trials: avoiding undue influence while distributing fairly the burdens of research participation. J Med Philos. 2009; 34 (1): 68–90.
  2. Stones M, McMillan J. Payment for participation in research: a pursuit for the poor. J Med Ethics. 2010; 36 (1): 34–36.
  3. Mareev IV, Samykina IA, Kolokoltsova MY, Pimenov ID, Tomofeev MS, Kulikov ES, et al. Motivatsiya i opyt uchastiya zdorovykh dobrovol’tsev v issledovaniyakh bioekvivalentnosti v Rossii. Razrabotka i registratsiya lekarstvennykh sredstv. 2018; (1): 198– 204. Russian.
  4. Ranjan R, Agarwal NB, Kapur P, Marwah A, Parveen R. Factors Influencing Participation Of Healthy Volunteers In Clinical Trials: Findings From A Cross-Sectional Study In Delhi, North India. Patient Prefer Adherence. 2019; 13: 2007–2015.
  5. Grady C, Bedarida G, Sinaii N, Gregorio MA, Emanuel EJ. Motivations, enrollment decisions, and socio-demographic characteristics of healthy volunteers in phase 1 research. Clin Trials. 2017; 14 (5): 526–536.
  6. Berg SL, Winick N, Ingle AM, Adamson PC, Blaney SM. Reasons for participation in optional pharmacokinetic studies in children with cancer: a Children’s Oncology Group phase 1 consortium study. Pediatr Blood Cancer. 2010; 55 (1): 119–122.
  7. Stunkel L, Grady C. More than the money: a review of the literature examining healthy volunteer motivations. Contemp Clin Trials. 2011; 32 (3): 342–352.
  8. Wang Z, Chen G, Liu X, Liu C, Song Q, Wang J. The motivations, barriers, and sociodemographic characteristics of healthy Chinese volunteers in phase I research. Eur J Clin Pharmacol. 2021; 77 (4): 557–568.
  9. Hassar M, Pocelinko R, Weintraub M, Nelson D, Thomas G, Lasagna L. Free-living volunteer’s motivations and attitudes toward pharmacologic studies in man. Clin Pharmacol Ther. 1977; 21 (5): 515–519.
  10. Cunny KA, Miller HW. Participation in clinical drug studies: motivations and barriers. Clin Ther. 1994; 16 (2): 273–282.
  11. Novak E, Seckman CE, Stewart RD. Motivations for volunteering as research subjects. J Clin Pharmacol New Drugs. 1977; 17 (7): 365–371.
  12. Almeida L, Azevedo B, Nunes T, Vaz-da-Silva M, Soares-da-Silva P. Why healthy subjects volunteer for phase I studies and how they perceive their participation? Eur J Clin Pharmacol. 2007; 63 (11): 1085–1094.
  13. van Gelderen CE, Savelkoul TJ, van Dokkum W, Meulenbelt J. Motives and perception of healthy volunteers who participate in experiments. Eur J Clin Pharmacol. 1993; 45 (1): 15–21.
  14. Kulikov SE, Deev IA, Kobjakova OS, Zvonareva OI, Fedorova OS, Kirillova NA, et al. Klinicheskoye issledovaniye glazami patsiyenta: motivatsiya, ozhidaniya, vospriyatiye. Klinicheskaya meditsina. 2016; 95 (8): 751–357. Russian.
  15. Chen SC, Sinaii N, Bedarida G, Gregorio MA, Emanuel E, Grady C. Phase 1 healthy volunteer willingness to participate and enrollment preferences. Clin Trials. 2017; 14 (5): 537–546.
  16. Weber JS, Kähler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012; 30 (21): 2691–2697.
  17. Fisher JA, McManus L, Cottingham MD, Kalbaugh JM, Wood MM, Monahan T et al. Healthy volunteers’ perceptions of risk in US Phase I clinical trials: A mixed-methods study. PLoS Med. 2018; 15 (11): e1002698.
  18. Emanuel EJ, Bedarida G, Macci K, Gabler NB, Rid A, Wendler D. Quantifying the risks of non-oncology phase I research in healthy volunteers: meta-analysis of phase I studies. BMJ. 2015; 350: h3271.
  19. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet. 2000; 356 (9237): 1255–1259.
  20. Friedman LM, Furberg CD, Demets DL, Reboussin DM, Granger CB, Moore TJ. Assessment and Reporting of Harm. In: Friedman LM, Furberg CD, DeMets DL, Reboussin DM, Granger CB, editors. Fundamentals of Clinical Trials. 5nd ed. New York, Dordrecht, London: Springer Cham Heidelberg, 2015; p. 255–277.
  21. Hermann R, Heger-Mahn D, Mahler M, Seibert-Grafe M, Klipping C, Breithaupt-Grögler K et al. Adverse events and discomfort in studies on healthy subjects: the volunteer’s perspective. A survey conducted by the German Association for Applied Human Pharmacology. Eur J Clin Pharmacol. 1997; 53 (3–4): 207–214.
  22. Dresser R. Subversive subjects: rule-breaking and deception in clinical trials. J Law Med Ethics. 2013; 41 (4): 829–840.
  23. Friedman LM, Furberg CD, DeMets DL. Assessing and Reporting Adverse Events. In: Friedman LM, Furberg CD, DeMets DL, editors. Fundamentals of Clinical Trials. New York: Springer, 2010; 215–231 p.
  24. Dickert N, Emanuel E, Grady C. Paying research subjects: an analysis of current policies. Ann Intern Med. 2002; 136 (5): 368– 373.
  25. Resnik DB, McCann DJ. Deception by Research Participants. N Engl J Med. 2015; 373 (13): 1192–1193.
  26. Devine EG, Waters ME, Putnam M, Surprise C, O’Malley K, Richambault C et al. Concealment and fabrication by experienced research subjects. Clin Trials. 2013; 10 (6): 935–948.
  27. McManus L, Fisher JA. To report or not to report: Exploring healthy volunteers’ rationales for disclosing adverse events in Phase I drug trials. AJOB Empir Bioeth. 2018; 9 (2): 82–90.
  28. Largent EA, Emanuel EJ, Lynch HF. Filthy Lucre or Fitting Offer? Understanding Worries About Payments to Research Participants. Am J Bioeth. 2019; 19 (9): 1–4.
  29. Gelinas L, Largent EA, Cohen IG, Kornetsky S, Bierer BE, Fernandez Lynch H. A Framework for Ethical Payment to Research Participants. N Engl J Med. 2018; 378 (8): 766–771.
  30. Largent EA, Lynch HF. Paying Research Participants: The Outsized Influence of “Undue Influence.” IRB. 2017; 39 (4): 1–9.
  31. The Association of the British Pharmaceutical Industry. Guidelines for Phase I clinical trials 2018 edition. The Association of the British Pharmaceutical Industry, 2019.
  32. Czarny MJ, Kass NE, Flexner C, Carson KA, Myers RK, Fuchs EJ. Payment to healthy volunteers in clinical research: the research subject’s perspective. Clin Pharmacol Ther. 2010; 87 (3): 286– 293.
  33. Fisher JA, McManus L, Kalbaugh JM, Walker RL. Phase I trial compensation: How much do healthy volunteers actually earn from clinical trial enrollment? Clin Trials. 2021; 18 (4): 477–487.
  34. Zanini GM, Marone C. A new job: research volunteer? Swiss Med Wkly. 2005; 135 (21–22): 315–317.
  35. Fitilev SB, Vozzhaev AV, Shkrebniova II, Kliuev DA. The problem of over-volunteering in early phase clinical trials. Good Clinical Practice. 2018; (2): 58–63. Russian.
  36. Bondareva IB, Bunjatjan ND, Zherdev VP, Kolyvanov GB, Kondratenko SN, Kukes VG i dr. Otsenka bioekvivalentnosti lekarstvennykh sredstv. Moskva: «Nauchnyy tsentr ekspertizy sredstv meditsinskogo primeneniya», 2008. Russian.
  37. WHO, Expert Committee on Specifications for Pharmaceutical Preparations. Guidance for organizations performing in vivo bioequivalence studies (Annex 9), WHO Technical Report Series No.996. WHO Expert Committee on Specifications for Pharmaceutical Preparations, 2016.