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The limitations of using randomised controlled trials as a basis for developing treatment guidelines
  1. Roger Mulder1,2,
  2. Ajeet B Singh1,3,
  3. Amber Hamilton1,4,5,6,
  4. Pritha Das1,4,5,6,
  5. Tim Outhred1,4,5,6,
  6. Grace Morris1,4,5,6,
  7. Darryl Bassett1,7,
  8. Bernhard T Baune1,8,
  9. Michael Berk1,3,9,
  10. Philip Boyce1,10,
  11. Bill Lyndon1,5,11,12,
  12. Gordon Parker1,13,14,
  13. Gin S Malhi1,4,6
  1. 1 Mood Assessment and Classification (MAC) Committee, Sydney, Australia
  2. 2 Department of Psychological Medicine, University of Otago, Christchurch, New Zealand
  3. 3 School of Medicine, IMPACT Strategic Research Centre, Deakin University, Barwon Health, Geelong, Victoria, Australia
  4. 4 Department of Psychiatry, Northern Sydney Local Health District, St Leonards, New South Wales, Australia
  5. 5 Sydney Medical School Northern, University of Sydney, Sydney, New South Wales, Australia
  6. 6 CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, New South Wales, Australia
  7. 7 Private Practice in Psychiatry and Division of Psychiatry, University of Western Australia, Perth, Australia
  8. 8 Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia
  9. 9 Department of Psychiatry, Orygen Research Centre, and the Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia
  10. 10 Discipline of Psychiatry, Sydney Medical School, Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia
  11. 11 Mood Disorders Unit, Northside Clinic, Greenwich, New South Wales, Australia
  12. 12 ECT Services, Northside Group Hospitals, Greenwich, New South Wales, Australia
  13. 13 School of Psychiatry, University of New South Wales, Kensington, New South Wales, Australia
  14. 14 Black Dog Institute, Sydney, New South Wales, Australia
  1. Correspondence to Professor Gin S Malhi, CADE Clinic, Academic Department of Psychiatry, Level 3, Main Building, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia; gin.malhi{at}


Randomised controlled trials (RCTs) are considered the ‘gold standard’ by which novel psychotropic medications and psychological interventions are evaluated and consequently adopted into widespread clinical practice. However, there are some limitations to using RCTs as the basis for developing treatment guidelines. While RCTs allow researchers to determine whether a given medication or intervention is effective in a specific patient sample, for practicing clinicians it is more important to know whether it will work for their particular patient in their particular setting. This information cannot be garnered from an RCT. These inherent limitations are exacerbated by biases in design, recruitment, sample populations and data analysis that are inevitable in real-world studies. While trial registration and CONSORT have been implemented to correct and improve these issues, it is worrying that many trials fail to achieve such standards and yet their findings are used to inform clinical decision making. This perspective piece questions the assumptions of RCTs and highlights the widespread distortion of findings that currently undermine the credibility of this powerful design. It is recommended that the clinical guidelines include advice as to what should be considered good and relevant evidence and that external bodies continue to monitor RCTs to ensure that the outcomes published indeed reflect reality.

  • protocols & guidelines
  • medical ethics
  • psychiatry
  • statistics & research methods
  • clinical trials

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  • Funding The MAC Project was supported logistically by Servier who provided financial assistance with travel and accommodation for those MAC Committee members travelling interstate or overseas to attend the meeting in Sydney (held on 18th March 2017). Members of the committee were not paid to participate in this project and Servier had no input into the content, format or outputs from this project.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Collaborators The Mood Assessment and Classification Committee (MAC Committee) comprised academic psychiatrists with clinical expertise in the management of mood disorders and researchers with an interest in depression and bipolar disorders. The independently convened committee specifically targeted contentious aspects of mood disorders diagnosis and assessment with the express aim of informing clinical practice and future research. Members of the committee held one face to face meeting in Sydney (Australia) to discuss the issues in depth and agree upon outcomes. These were then developed further via email correspondence.