Review
From Randomized Controlled Trials to Observational Studies

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Abstract

Randomized controlled trials are considered the gold standard in the hierarchy of research designs for evaluating the efficacy and safety of a treatment intervention. However, their results can have limited applicability to patients in clinical settings. Observational studies using large health care databases can complement findings from randomized controlled trials by assessing treatment effectiveness in patients encountered in day-to-day clinical practice. Results from these designs can expand upon outcomes of randomized controlled trials because of the use of larger and more diverse patient populations with common comorbidities and longer follow-up periods. Furthermore, well-designed observational studies can identify clinically important differences among therapeutic options and provide data on long-term drug effectiveness and safety.

Section snippets

Randomized Controlled Trials

Randomized controlled trials are the main means of establishing the efficacy of lifestyle interventions or treatment approaches (or both) in well-defined populations of healthy and diseased individuals. During drug development and early testing, randomized, placebo-controlled trials use precise clinical endpoints to determine the efficacy and safety of a new drug administered under strictly controlled conditions. Such studies are designed to minimize threats to internal validity, thus ensuring

Observational Studies

Observational studies can have a case-control or a cohort design. Case-control studies identify cases with and without the relevant outcome, then the effect of treatment or exposure is compared between the 2 groups of patients.13, 14 Because the research process involves looking back in time, case-control studies also are called retrospective studies. In cohort studies, patients are selected and subsequently observed over time for effects of treatment or exposure on the relevant outcome.14

Conclusions

Although randomized controlled trials are considered the gold standard in assessing treatment efficacy and safety of newly developed drugs, their results can be limited when applied to real-world clinical settings. Observational studies assess treatment effectiveness in patients in day-to-day clinical practice. Results from these studies can confirm and expand upon outcomes reported for selected populations in randomized controlled trials. Controlled head-to-head comparisons of therapies are

References (33)

  • M. McKee et al.

    Methods in health services researchInterpreting the evidence: choosing between randomised and non-randomised studies

    BMJ

    (1999)
  • R.J. Goldberg et al.

    Enhancing peer review of scientific manuscripts

    Arch Intern Med

    (1997)
  • A.Y. Khan et al.

    Effect of study criteria on recruitment and generalizability of the results

    J Clin Psychopharmacol

    (2005)
  • M. Zimmerman et al.

    Generalizability of antidepressant efficacy trials: differences between depressed psychiatric outpatients who would or would not qualify for an efficacy trial

    Am J Psychiatry

    (2005)
  • J.K. Lee et al.

    Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial

    JAMA

    (2006)
  • J.A. Ioannidis et al.

    Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas

    JAMA

    (2001)
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    Funding: The author received editorial support in the preparation of this manuscript funded by The Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and sanofi-aventis U.S., Inc). The author, however, was fully responsible for all content and editorial decisions and received no financial support or other form of compensation related to the development of the article.

    Conflict of interest: The author is a consultant and speaker for The Alliance for Better Bone Health and has received research grant support.

    Authorship: The author had access to the data and maintained complete control of manuscript development.

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