Can systematic reviews contribute to regulatory decisions?



The new call on independent research on drugs issued in October 2016 by the Italian Medicines Agency (AIFA) explicitly reported that proposals based on systematic reviews were not admissible, and no justification or explanation for this choice was given. Prompted by this policy decision, here, we briefly discuss the potential usefulness of systematic reviews in responding to regulatory needs. First, systematic reviews, by collecting, analysing and critically appraising all relevant studies on a specific topic, may be used by different stakeholders as a basis for making clinical and policy recommendations, including regulatory recommendations. Second, systematic reviews may advance knowledge as primary clinical research does. Third, systematic reviews may be particularly useful to detect signals of unknown adverse effects. Fourth, systematic reviews may be used to identify knowledge gaps.


Systematic reviews may simultaneously produce new findings and summarize existing knowledge, with the potential of informing regulatory decisions more pragmatically and more rapidly than other research designs. We suggest that national and international calls on independent research on drugs should not put primary clinical research against systematic reviews, as it implies a focus on the methods instead of on the questions being asked. As most calls only broadly define the research areas and the topics to be covered, we argue that it should be up to the applicant to make a proposal on which design provides the most valid and useful answer, and up to the assessors to carefully check the validity, feasibility and relevance of such a proposal.

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  1. 1.

    Agenzia Italiana del Farmaco (2016) AIFA: online il bando 2016 per la ricerca indipendente. Available from:

  2. 2.

    Italian Medicines Agency (AIFA) Research & Development Working Group (2010) Feasibility and challenges of independent research on drugs: the Italian medicines agency (AIFA) experience. Eur J Clin Investig 40:69–86

    Article  Google Scholar 

  3. 3.

    Cook DJ, Mulrow CD, Haynes RB (1997) Systematic reviews: synthesis of best evidence for clinical decisions. Ann Intern Med 126:376–380

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Haynes RB, Devereaux PJ, Guyatt GH (2002) Physicians’ and patients’ choices in evidence based practice. BMJ 324:1350

    Article  PubMed  Google Scholar 

  5. 5.

    Laughren T (2006) Briefing document for December 13 meeting of Psychopharmacologic Drugs Advisory Committee. Available from:

  6. 6.

    Stone M, Laughren T, Jones L, Levenson M, Holland PC, Hughes A (2009) Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ 339. doi:10.1136/bmj.b2880.

  7. 7.

    Barbui C, Cipriani A, Geddes JR (2008) Antidepressants and suicide symptoms: compelling new insights from the FDA’s analysis of individual patient level data. Evid Based Ment Health 11:34–35

    Article  PubMed  Google Scholar 

  8. 8.

    Wooltorton E (2002) Risperidone (Risperdal): increased rate of cerebrovascular events in dementia trials. CMAJ 167:1269–1270

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Wooltorton E (2004) Olanzapine (Zyprexa): increased incidence of cerebrovascular events in dementia trials. CMAJ 170:1395

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Schneider LS, Dagerman KS, Insel P (2005) Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 294:1934–1943

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Barbui C, Baschirotto C, Cipriani A (2011) EMA must improve the quality of its clinical trial reports. BMJ 342:d2291

    Article  PubMed  Google Scholar 

  12. 12.

    Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F et al (2013) Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382:951–962

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Ciliska D, Peirson L, Muresan J (2007) Public health knowledge gaps and research priorities: a synthesis of next steps. Available from:

  14. 14.

    Traversa G, Masiero L, Sagliocca L, Trotta F (2016) Italian program for independent research on drugs: 10-year follow-up of funded studies in the area of rare diseases. Orphanet J Rare Dis 11:36

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Sackett DL, Wennberg JE (1997) Choosing the best research design for each question. BMJ 315:1636

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Authors’ contribution

C Barbui wrote the first draft. All authors contributed to the writing, revised the text critically, and approved the final version.

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Correspondence to Corrado Barbui.

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Barbui, C., Addis, A., Amato, L. et al. Can systematic reviews contribute to regulatory decisions?. Eur J Clin Pharmacol 73, 507–509 (2017).

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  • Systematic reviews
  • Regulatory science
  • Meta-analysis