Skip to main content
SpringerLink
Log in

Evidence-Based Medicine and Rare Diseases

  • Chapter
  • First Online:
Book cover Rare Diseases Epidemiology: Update and Overview

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1031))

Abstract

This chapter discusses the meaning of evidence-based medicine and where it relates to randomised controlled trials, but also where it does not. The need for good quality evidence is stressed through a discussion of high failure rates in drug development and arguments against access to unlicensed (and largely untested) treatments are set out (despite the good intentions of those who advocate such access to treatments).

Good quality, reliable evidence does not always have to come from clinical trials. Other forms of evidence are discussed. Meta-analyses of individual trials may help to resolve the problem that, in rare diseases, it may be very difficult or impossible to do adequately powered clinical trials – but that does not imply those trials have no value at all.

The importance of patients’ choices is stressed but the difficulties of making choices and the general poor understanding of risk can make patients and caregivers, as well as healthcare professionals, very vulnerable to making poor decisions. All stakeholders need to be adequately guided through the evidence to make proper informed decisions.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Booth B, Glassman R, Ma P (2003) Oncology’s trials. Nature Rev. Drug Discov 2:609–610

    Article  CAS  Google Scholar 

  2. Chalmers TC (1968) When should randomisation begin? Lancet 1(7547):858

    Article  CAS  PubMed  Google Scholar 

  3. Chalmers TC (1975) Randomization of the first patient. Med Clin North Am 59:1035–1038

    Article  CAS  PubMed  Google Scholar 

  4. Chalmers TC (1977) Randomize the first patient! N Engl J Med 296:107

    CAS  PubMed  Google Scholar 

  5. Committee for Medicinal Products for Human Use (CHMP) (2006) Guideline on clinical trials in small populations. European Medicines Agency, London

    Google Scholar 

  6. Day S (2009) Bayesian statistics. DIA global. Forum 1(6):34–35

    Google Scholar 

  7. DiMasi JA (2001) Risks in new drug development: approval success rates for investigational drugs. Clin Pharm Therap 69:297–307

    Article  CAS  PubMed  Google Scholar 

  8. GovTrack.US (2005) United States Senate Bill S.1956 – 109th Congress. To amend the Federal Food, drug and Cosmetic Act to create a new three-tiered approval system for drugs, biological products, and devices that is responsive to the needs of seriously ill patients, and for other purposes. http://www.govtrack.us/congress/bill.xpd?bill=s109-1956. Cited 31st Dec 2009

  9. GRADE Working Group (2004) Grading quality of evidence and strength of association. Brit Med J 328:1490–1494

    Article  PubMed Central  Google Scholar 

  10. Green SB, Byar DP (1984) Using observational data from registries to compare treatments: the fallacy of omnimetrics. Stat Med 3:361–370

    Article  CAS  PubMed  Google Scholar 

  11. Hill AB (1951) The clinical trial. Brit Med Bull 7:278–282

    Article  CAS  PubMed  Google Scholar 

  12. Hill AB (1965) The environment and disease: association or causation? Proc Roy Soc Med 58:295–300

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Institute of Medicine (2001) Small clinical trials: issues and challenges. National Academic Press, Washington, DC

    Google Scholar 

  14. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (2000) ICH Harmonised Tripartite Guideline Choice of Control Group and Related Issues in Clinical Trials E10. International Conference on Harmonisation. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E10/Step4/E10_Guideline.pdf. Accessed 17 Oct 2016

  15. Kola I, Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nature Rev Drug Discov 3:711–715

    Article  CAS  Google Scholar 

  16. Malenka DJ, Baron JA, Johansen S, Wahrenberger JW, Ross JM (1993) The framing effect of relative and absolute risk. J Gen Int Med 8:543–548

    Article  CAS  Google Scholar 

  17. Mangset M, Berge E, Førde R, Nessa J, Wyller TB (2009) “Two per cent isn’t a lot, but when it comes to death it seems quite a lot anyway”: patients’ perception of risk and willingness to accept risks associated with thrombolytic drug treatment for acute stroke. J Med Ethics 35:42–46

    Article  CAS  PubMed  Google Scholar 

  18. Matthews JNS (1995) Small clinical trials: are they all bad? Stat Med 14:115–126

    Article  CAS  PubMed  Google Scholar 

  19. Moyé LA (2008) Bayesians in clinical trials: asleep at the switch. Stat Med 27:469–482

    Article  PubMed  Google Scholar 

  20. Mussen F, Salek S, Walker S (2009) Benefit-risk appraisal of medicines. A systematic approach to decision-making. Wiley-Blackwell, Chichester

    Google Scholar 

  21. Okie S (2006) Access before approval – a right to take experimental drugs? N Engl J Med 355:437–440

    Article  CAS  PubMed  Google Scholar 

  22. Pearson H (2006) The bitterest pill. Nature 444:532–533

    Article  CAS  Google Scholar 

  23. Phillips CV (2001) The economics of ‘more research is needed’. Int J Epidem 30:771–776

    Article  CAS  Google Scholar 

  24. Piantadosi S (1990) Editorial. Hazards of small clinical trials. J Clin Oncol 8:1–3

    Article  CAS  PubMed  Google Scholar 

  25. Po LW (1998) Dictionary of evidence based medicine. Radcliffe Medical Press, Oxford

    Google Scholar 

  26. Reidenberg MM (1987) Should unevaluated therapies be available for sale? Clin Pharmacol Ther 42:599–600

    Article  CAS  PubMed  Google Scholar 

  27. Sackett DL, Rosenberg WMC, Gray JAM, Haynes RB, Richardson WS (1996) Editorial. Evidence based medicine: what it is and what it is not. Brit Med J 312:71–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Saver JL (1995) Coping with an embarrassment of riches. Stroke 26:1289–1292

    Article  CAS  PubMed  Google Scholar 

  29. Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou GG (2008) Interpreting results and drawing conclusions. In: Higgins JPT, Green S (eds) Cochrane handbook for systematic reviews of interventions. Wiley, Chichester

    Google Scholar 

  30. Society for Clinical Trials Board of Directors (2006) The Society for Clinical Trials opposes US legislation to permit marketing of unproven medical therapies for seriously ill patients. Clin Trials 3:154–157

    Article  Google Scholar 

  31. Spodick DH (1983) Randomize the first patient: Scientific, ethical, and behavioral bases. Am J Cardiol 51:916–917

    Article  CAS  PubMed  Google Scholar 

  32. Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F (2000) Methods for meta-analysis in medical research. Wiley, Chichester

    Google Scholar 

  33. Tan S-B, Dear KBG, Bruzzi P, Machin D (2003) Strategy for randomised clinical trials in rare cancers. Brit Med J 327:47–49

    Article  PubMed  PubMed Central  Google Scholar 

  34. United States Department of Health and Human Services (2009) Code of federal regulations 21 CFR 314.126. Adequate and well controlled studies. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm. Accessed 17 Oct 2016

  35. Whitehead A (2002) Meta-analysis of controlled clinical trials. Wiley, Chichester

    Book  Google Scholar 

  36. World Medical Association (2013) World medical association declaration of Helsinki – ethical principles for medical research involving human subjects. JAMA 310:2191–2194

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Trials Consulting & Training Limited, 53 Portway, North Marston, Buckinghamshire, MK18 3PL, UK

    Simon Day

Authors
  1. Simon Day
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simon Day .

Editor information

Editors and Affiliations

  1. RDR and CIBERER, Instituto de Salud Carlos III, Madrid, Spain

    Manuel Posada de la Paz

  2. Centro Nazionale Malattie Rare, Istituto Superiore di Sanita, Roma, Italy

    Domenica Taruscio

  3. National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA

    Stephen C. Groft

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Day, S. (2017). Evidence-Based Medicine and Rare Diseases. In: Posada de la Paz, M., Taruscio, D., Groft, S. (eds) Rare Diseases Epidemiology: Update and Overview. Advances in Experimental Medicine and Biology, vol 1031. Springer, Cham. https://doi.org/10.1007/978-3-319-67144-4_12

Download citation

Publish with us

Policies and ethics

Search

Navigation