Skip to main content
SpringerLink
Log in

Standards of Research for Clinical Trials in Low- and Middle-Income Countries

  • Chapter
Optimizing Treatment for Children in the Developing World

  • 568 Accesses

Abstract

Research supporting the effectiveness and safety of medications for young children in low- and middle-income countries (LMIC) can only be generated if high-quality randomized controlled trials are designed, conducted, and reported appropriately. Clinical research in LMIC is associated with ethical and scientific risks beyond those observed in high-income countries. Scientific challenges of clinical research in LMIC include the need to contain risks of trial bias related to attrition and blinding, definition of the role of data monitoring committees, valid measurement of relevant and standardized outcomes, and inclusion of the appropriate paediatric age sub-groups; ethical challenges particular to clinical research in LMIC include conduct of placebo-controlled clinical trials despite HIC availability of effective comparator interventions, obtaining informed consent despite power inequities, and the obligation to redress health disparities in LMIC. This chapter addresses challenges and proposes ways to navigate these challenges through awareness, regulatory oversight, consultation, and strengthened collaboration with investigators and communities.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Conroy S, Choonara I, Impicciatore P, et al. Survey of unlicensed and off label drug use in paediatric wards in European countries. European Network for Drug Investigation in Children. Br Med J. 2000;320:79–82.

    Article  CAS  Google Scholar 

  2. t’Jong GW, Vulto AG, de Hoog M, Schimmel KJ, Tibboel D, van den Anker JN. Unapproved and off-label use of drugs in a children’s hospital. N Engl J Med. 2000;343:1125.

    Article  Google Scholar 

  3. Klassen TP, Hartling L, Craig JC, Offringa M. Children are not just small adults: the urgent need for high-quality trial evidence in children. PLoS Med. 2008;5:e172.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Cohen E, Uleryk E, Jasuja M, Parkin PC. An absence of pediatric randomized controlled trials in general medical journals, 1985–2004. J Clin Epidemiol. 2007;60:118–23.

    Article  PubMed  Google Scholar 

  5. Wittmeier KD, Craig J, Klassen TP, Offringa M. The mission of StaR Child Health is to improve the quality of the design, conduct, and reporting of pediatric clinical research by promoting the use of modern research standards. Introduction. Pediatrics. 2012;129 Suppl 3:S111.

    Article  PubMed  Google Scholar 

  6. Standards for Research (StaR) in Child Health. http://www.starchildhealth.org. Accessed 15 Oct 2014.

  7. Klassen TP, Hartling L, Hamm M, van der Lee JH, Ursum J, Offringa M. StaR Child Health: an initiative for RCTs in children. Lancet. 2009;374:1310–2.

    Article  PubMed  Google Scholar 

  8. Frakking FN, van der Lee JH, Klassen TP, Offringa M for the STaR-Child Health Group. Survey of current guidance for child health clinical trials. The StaR Child Health Project: standards for research in children. 2009. www.who.int/childmedicines/publications/GUIDANCECHILDHEALTH.pdf. Accessed 14 Oct 2014.

  9. Council of Canadian Academies. Improving current approaches to paediatric efficacy studies. In: Improving Medicines for Children in Canada. 2014. http://www.scienceadvice.ca/en/news.aspx?id=139. Accessed 15 Oct 2014.

  10. Chan A-W, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin J, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. Br Med J. 2013;346:e7586.

    Article  Google Scholar 

  11. Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Ann Intern Med. 2010;11:32.

    Google Scholar 

  12. Bernard C. An introduction to the study of experimental medicine. 2nd ed. New York: Dover Publications; 1957.

    Google Scholar 

  13. Shuster E. Fifty years later: the significance of the Nuremberg Code. N Engl J Med. 1997;337:1436–40.

    Article  CAS  PubMed  Google Scholar 

  14. World Medical Association. Declaration of Helsinki. Ethical principles for medical research involving human subjects. Seoul: Amended by the World Medical Association 59th General Assembly; 2008.

    Google Scholar 

  15. Council for International Organizations of Medical Sciences. International ethical guidelines for biomedical research involving human subjects. Geneva: Council for International Organizations of Medical Sciences; 2002.

    Google Scholar 

  16. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Belmont Report. Ethical principles and guidelines for the protection of human subjects of research. Washington: Government Printing Office; 1988. GPO 887–809.

    Google Scholar 

  17. Nuffield Council on Bioethics. Ethical issues in research in developing countries. London: Nuffield Council on Bioethics discussion paper; 1999.

    Google Scholar 

  18. National Bioethics Advisory Commission. Ethical and policy issues in international research. Washington: National Bioethics Advisory Commission; 2000.

    Google Scholar 

  19. Weijer C, Emanuel EJ. Protecting communities in biomedical research. Science. 2000;289:1142–4.

    Article  CAS  PubMed  Google Scholar 

  20. Annas GJ, Grodin MA. Human rights and maternal-fetal HIV transmission prevention trials in Africa. Am J Public Health. 1998;88:560–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Gambia Hepatitis Study Group. Hepatitis B vaccine in the expanded programme on immunization: the Gambian experience. Lancet. 1989;i:1057–60.

    Article  Google Scholar 

  22. Mulholland EK, Hilton S, Adegbola R, Usen S, Oparaugo A, Omoshigo C, et al. Randomised trial of a Haemophilus influenzae type-b tetanus protein conjugate vaccine [corrected] for prevention of pneumonia and meningitis in Gambian infants. Lancet. 1997;349:1191–7.

    Article  CAS  PubMed  Google Scholar 

  23. Vimolket T, Theamboonlers A, Dumas R, Milcamps B, Forrat R, Poovorawan Y. Immunogenicity and safety of a new inactivated hepatitis A vaccine in Thai young adults. Southeast Asian J Trop Med Public Health. 1998;29:779–85.

    CAS  PubMed  Google Scholar 

  24. Bhutta ZA, Capeding MR, Bavdekar A, Marchetti E, Ariff S, Soofi SB, et al. Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: results from two randomised, observer-blind, age de-escalation, phase 2 trials. Lancet Infect Dis. 2014;14:119–29.

    Article  CAS  PubMed  Google Scholar 

  25. Watanaveeradej V, Gibbons RV, Simasathien S, Nisalak A, Jarman RG, Kerdpanich A, et al. Safety and immunogenicity of a rederived, live-attenuated dengue virus vaccine in healthy adults living in Thailand: a randomized trial. Am J Trop Med Hyg. 2014;91:119–28.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Mulholland K. Pneumococcal conjugate vaccine relevance for developing countries. Indian Pediatr. 2001;38:453–60.

    CAS  PubMed  Google Scholar 

  27. Varmus H, Satcher D. Ethical complexities of conducting research in developing countries. N Engl J Med. 1997;337:1003–5.

    Article  CAS  PubMed  Google Scholar 

  28. Benatar SR, Singer PA. A new look at international research ethics. Br Med J. 2000;321:824–6.

    Article  CAS  Google Scholar 

  29. Copenhagen (World Pharma 2010). Challenges in the conduct of pediatric clinical trials in low and middle income countries. http://www.micyrn.ca/francais/PDF/starfinal.pdf. Accessed 16 Oct 2014.

  30. Kass N, Hyder A. Attitudes and experiences of US and developing country investigators regarding US human subjects regulations. In: National Bioethics Advisory Commission, editor. Ethical and policy issues in international research: clinical trials in developing countries, vol. II. Bethesda: National Bioethics Advisory Commission; 2001.

    Google Scholar 

  31. Bhutta ZA. Ethics in international health research: a perspective from the developing world. Bull World Health Organ. 2002;80:114–20.

    PubMed Central  PubMed  Google Scholar 

  32. Bhutta ZA. Beyond informed consent. Bull World Health Organ. 2004;82:771–7.

    PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgement

Dr. William van’t Hoff from the Somers Clinical Research Facility, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom, helped in preparing parts of this text.

Author information

Authors and Affiliations

  1. Centre for Global Child Health, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada

    Zulfiqar A. Bhutta PhD, MBBS

  2. Nutritional Sciences and Public Health, University of Toronto, Toronto, ON, Canada

    Zulfiqar A. Bhutta PhD, MBBS

  3. Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada

    Martin Offringa MD, PhD

  4. Department of Pediatrics, University of Toronto, Toronto, ON, Canada

    Martin Offringa MD, PhD

Authors
  1. Zulfiqar A. Bhutta PhD, MBBS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin Offringa MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin Offringa MD, PhD .

Editor information

Editors and Affiliations

  1. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada

    Stuart MacLeod

  2. University of Melbourne Medical School, Melbourne, VIC, Australia

    Suzanne Hill

  3. Departments of Pediatrics and Pharmacology, University of Toronto, Toronto, Ontario, Canada

    Gideon Koren

  4. Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University, Hostpital Karolinska Institutet, Stockholm, Sweden

    Anders Rane

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bhutta, Z.A., Offringa, M. (2015). Standards of Research for Clinical Trials in Low- and Middle-Income Countries. In: MacLeod, S., Hill, S., Koren, G., Rane, A. (eds) Optimizing Treatment for Children in the Developing World. Adis, Cham. https://doi.org/10.1007/978-3-319-15750-4_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-15750-4_14

  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-15749-8

  • Online ISBN: 978-3-319-15750-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation