Medical Writing Preclinical Studies The reproducibility crisis in preclinical research – lessons to learn from clinical research

Volume 26, Issue 4 - Preclinical Studies

The reproducibility crisis in preclinical research – lessons to learn from clinical research


In recent years, the robustness and reproducibility of preclinical data have been a topic for discussion. Quality standards and good practices are often not well defined for different in vitro methods and in vivo models,
and not harmonised amongst preclinical research laboratories. This results in poorly reliable literature, has a negative impact on the bench-to-bedside time for new drugs, and increases the resources needed for clinical development. Clinical research, on the other hand, is tightly regulated and has high quality standards in place. Although improvements are slowly introduced, preclinical development (especially in its confirmatory phases)
would benefit from taking a closer look and adapting more of the internationally accepted
principles used in clinical research.
Download the full article


  1. Baker M. Is there a reproducibility crisis? Nature. 2016;533(7604):452–4. Available from: http://
  2. Prinz F, Schlange T, Asadullah K. Believe it or not: How much can we rely on published data on potential drug targets? Nat Rev Drug Discov. 2011;10(9):712–3. Available from: http://
  3. Begley CG, Ellis LM. Drug development: Raise standards for preclinical cancer research. Nature. 2012;483(7391):531–3. Available from: http://
  4. Osherovich L. Hedging against academic risk. SciBX 2011;4. Available from: http://
  5. Freedman LP, Cockburn IM, Simcoe TS. The economics of reproducibility in preclinical research. PLoS Biol. 2015;13(6):e1002165. Available from: http://
  6. Macleod MR, van der Worp HB, Sena ES, Howells DW, Dirnagl U, Donnan GA. Evidence for the efficacy of NXY-059 in experimental focal cerebral ischaemia is confounded by study quality. Stroke. 2008;39(10):2824–9. Available from: http://
  7. International Cell Line Authentication Committee (ICLAC). [cited 2017 November 13]. Available from:
  8. Perrin S. Preclinical research: Make mouse studies work. Nature 2014;507(7493): 423–5. Available from: http://
  9. Good Laboratory Practices (GLP) for Non-Clinical Laboratory Studies, 21 C.F.R. Part 58. [cited 2017 November 13]. Available from: 1ohrms/ dockets/98fr/980335s1.pdf
  10. Directive 2004/10/EC of the European Parliament and of the Council of 11 February 2004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances. Official J Eur Comm. 2004;L50/44. [cited 2017 November 13]. Available from: directive_2004_10_ec.pdf
  11. Directive 2004/9/EC of the European Parliament and of the Council of 11 February 2004 on the inspection and verification of good laboratory practice (GLP). Official J Eur Comm. 2004;L50/28. [cited 2017 November 13]. Available from: cm/349/directive_2004_9_ec.pdf
  12. 89/569/EEC Council Decision of 28 July 1989 on the acceptance by the European Economic Community of an OECD decision/recommendation on compliance with principles of good laboratory practice. Official J Eur Comm. 1989;L315/32. [cited 2017 November 13]. Available from: EN/TXT/?uri=OJ:L:1989:315:TOC
  13. Carlisle JB. Data fabrication and other reasons for non-random sampling in 5087 randomised, controlled trials in anaesthetic and general medical journals. Anaesthesia. 2017;72(8):944–52. Available from: http://
  14. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the care and use of laboratory animals. 8th edition. Washington (DC): National Academies Press (US); 2011. Available from: http://
  15. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official J Eur Comm. 2010;L276/33. [cited 2017 November 13]. Available from: EN/TXT/?uri=celex%3A32010L0063
  16. Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC). [cited 2017 November 13]. Available from:
  17. International Council for Laboratory Animal Science (ICLAS). [cited 2017 November 13]. Available from:
  18. Coecke S, Balls M, Bowe G, Davis J, Gstraunthaler G, Hartung T, et al. Guidance on good cell culture practice. A report of the second ECVAM task force on good cell culture practice. Altern Lab Anim. 2005;33(3):261–87. Available from: http://
  19. Voelkl B, Würbel H. Reproducibility crisis: Are we ignoring reaction norms? Trends Pharmacol Sci. 2016;37(7):509–10. Available from: http://
  20. EMA/240810/2013, POLICY/0070 of 2 October 2014. European Medicines Agency policy on publication of clinical data for medicinal products for human use. [cited 2017 November 13]. Available from: document_library/Other/2014/10/ WC500174796.pdf
  21. Nosek BA, Alter G, Banks GC, Borsboom D, Bowman SD, Breckler SJ, et al. Promoting an open research culture: Author guidelines for journals could help to promote transparency, openness, and reproducibility. Science. 2015;348(6242): 1422–5. Available from: http://
  22. Pavlica S. The need for registration of preclinical studies. Med Writ. 2013;22(2):131–3. Available from: http://
  23. Consolidated Standards of Reporting Trials (CONSORT) statement. [cited 2017 November 13]. Available from:
  24. Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. [cited 2017 November 13]. Available from:
  25. Structured Transparent Accessible Reporting (STAR) Methods. [cited 2017 November 13]. Available from:
  26. Brazma A, Hingamp P, Quackenbush J, Sherlock G, Spellman P, Stoeckert C, et al. Minimum information about a microarray experiment (MIAME) toward standards for microarray data. Nat Genet. 2001;29(4):365–71. Available from: http://
  27. collections. Minimum Information for Biological and Biomedical Investigations (MIBBI). [cited 2017 November 13]. Available from:
  28. Kimmelman J, Mogil JS, Dirnagl U. Distinguishing between exploratory and confirmatory preclinical research will improve translation. PLOS Biol. 2014;12(5):e1001863. Available from: http://



Preclinical studies
President’s Message
EMWA celebrates 25 years
Preclinical research in drug development
An introduction to little-known aspects of nonclinical regulatory writing
Reporting of preclinical research: What do we get told – when and how?
Mind the gap – towards complete and transparent reporting of animal research
The reproducibility crisis in preclinical research – lessons to learn from clinical research
Nonclinical studies in the Russian Federation — Problems, regulatory norms, and harmonisation with international standards
How to survive Brexit as an independent medical writer
Creation of a patient-centric patient lay summary in the local language
Six communication rules for scientific presentations and writing
So, you want to be a medical journalist?
News from the EMA
Profile: An interview with Steven Walker
Getting Your Foot in the Door
In the Bookstores
Journal Watch
The Webscout
Good Writing Practice
Medical Communications
Out on Our Own


The Write Stuff Archive Contact Instructions for Authors Article Template (Word) Journal Policies

Editoral Board


Raquel Billiones


Evguenia Alechine

Jonathan Pitt

Managing Editor

Victoria White

Deputy Managing Editor

Alicia Brooks Waltman

Associate Editors

Anuradha Alahari

Jennifer Bell

Nicole Bezuidenhout

Claire Chang

Barbara Grossman

Sarah Milner

John Plant

Sampoorna Rappaz

Amy Whereat

Section Editors

Daniela Kamir


Jennifer Bell


Nicole Bezuidenhout 

Digital Communication

Somsuvro Basu

EMWA News 

Ana Sofia Correia 

Gained in Translation

Ivana Turek

Getting Your Foot in the Door

Wendy Kingdom / Amy Whereat

Good Writing Practice

Alison McIntosh 

In the Bookstores

Maria Kołtowska-Häggström

Lingua Franca and Beyond

Maddy Dyer


Lisa Chamberlain-James

Medical Communications/Writing for Patients

Payal Bhatia

Medical Devices

Evguenia Alechine

My First Medical Writing

Anuradha Alahari

News from the EMA

Adriana Rocha


Tiziana von Bruchhausen


Clare ChangZuo Yen Lee 

Regulatory Matters

Sam Hamilton

Regulatory Public Disclosure

Claire Gudex

Teaching Medical Writing

Louisa Ludwig-Begall / Sarah Kabani

The Crofter: Sustainable Communications

Louisa Marcombes

Veterinary Writing

Editors Emeritus

Elise Langdon-Neuner

Phil Leventhal

Layout Designer

Chris Monk