Cited by 54Attention Deficit Hyperactivity DisorderEthics in Clinical ResearchPharmaceutical studies and practices

Representativeness of Participants in a Clinical Trial for Attention-Deficit/Hyperactivity Disorder?: Comparison With Adults From a Large Observational Study

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Surman, Craig B. H., Monuteaux, Michael C., Petty, Carter R., Faraone, Stephen V., Spencer, Thomas J., Chu, Nicole F., Biederman, Joseph·2010·The Journal of Clinical Psychiatry

Abstract

Article AbstractBackground: Clinical trials have demonstrated that pharmacotherapies can safely treat attention-deficit/hyperactivity disorder (ADHD) in adulthood. Eligibility criteria in these trials may significantly limit their external validity by excluding a significant portion of adults with ADHD in the general population. In particular, exclusion criteria may frequently exclude individuals with comorbid mental health conditions, which are common in the adult ADHD population. Method: We addressed the representativeness of clinical trials by comparing 146 adult clinical trial participants with DSM-IV ADHD and a community sample composed of 124 adults with DSM-IV ADHD and 123 non-ADHD controls. Subjects were compared on socioeconomic status, Hollingshead occupational code, cognitive measures, lifetime psychopathology, and Global Assessment of Functioning (GAF) scale ratings. Results: Adults with ADHD in the community sample had higher rates of lifetime psychiatric comorbidity, lower GAF scores, and lower occupational codes than those in the clinical trial. The clinical trial eligibility criteria would have excluded 61% of community sample adults with ADHD. This excluded portion of the community sample had higher rates of lifetime psychiatric comorbidity and lower GAF scores than clinical trial participants. Conclusions: Adults with ADHD participating in the clinical trial had less evidence of functional impairment and endorsed less psychiatric comorbidity than the majority of community sample subjects with ADHD. This suggests that findings from clinical trials may have limited external validity for adults with ADHD in the general population, particularly for those adults with ADHD with the greatest burden of comorbid psychopathology.J Clin PsychiatrySubmitted: May 08, 2009; accepted July 14, 2009. Online ahead of print: August 10, 2010 (doi:10.4088/JCP.09m05344pur). Corresponding author: Craig B. H. Surman, MD, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Ste 2000, 185 Alewife Brook Pkwy, Cambridge, MA 02138 (csurman@partners.org).

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  • Findings from one RCT in US adults with ADHD suggest that approximately 31% of individuals with ADHD presenting for routine clinical care would meet eligibility for participation in the RCT.

    “Findings from one RCT in US adults with ADHD suggest that approximately 31% of individuals with ADHD presenting for routine clinical care would meet eligibility for participation in the RCT.8”

    From Evaluating ADHD medication trial representativeness: a Swedish population-based study comparing hypothetically trial-eligible and trial-ineligible individuals (2025) · cites this paper as [8]

    The Results and Discussion report that 61% of the community sample would have been ineligible, implying 39% eligible—not approximately 31%. The Methods also say the community sample came from both hospital referrals and advertisements, rather than solely from people presenting for routine clinical care. (LLM, conf=0.88)

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  • Randomized trial conclusions are limited by sample sizes and treatment lengths too short to detect rare but serious substance-related events, by generalizability questions, and by ethical concerns about withholding effective treatment.

    “Conclusions from randomized clinical trials have been constrained by sample sizes and treatment durations that may be insufficient to detect rare-yet-serious substance-related events, questions regarding generalizability, and ethical concerns about withholding efficacious treatments (24, 25).”

    From ADHD Medication and Substance-Related Problems (2017) · cites this paper as [25]

    The Introduction and Discussion (pages not provided) support the generalizability concern: adults in ADHD trials may not represent adults with ADHD in the community. The paper describes a six-week trial and exclusions for substance abuse, but does not say that trial size or duration prevents detection of rare serious substance-related events, or discuss ethical concerns about withholding effective treatment. (LLM, conf=0.88)

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  • The percentage of ineligible adults in this study aligns with the 61% of adults with ADHD in a community sample reported by Surman and colleagues to be excluded due to stringent eligibility criteria.

    “The percentage of ineligible adults aligns with that previously reported in one single RCT by Surman and colleagues,8 who found that 61% of adults with ADHD in a community sample would be excluded due to stringent eligibility criteria.”
  • These findings are based on one RCT in a specific country and refer to adults only.

    “However, these findings are based on one RCT in a specific country and refer to adults only.”

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Research works printed but not linked: 2

  1. [5]First M Spitzer R Gibbon M Structured Clinical Interview for DSM-IV Axis I Disorders 1997 American Psychiatric Press Washington, DC
  2. [9]Hollingshead AB Four Factor Index of Social Status 1975 Yale University Press New Haven, CT

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Authors
Surman, C. B. H., Monuteaux, M. C., Petty, C. R., Faraone, S. V., Spencer, T. J., Chu, N. F., & Biederman, J.
Affiliations
  • Massachusetts General Hospital (US)
  • SUNY Upstate Medical University (US)
Corresponding author
Surman, Craig B. H.
Venue
The Journal of Clinical Psychiatry
Published
2010-08-10
Volume
71
Issue
12
Pages
1612-1616
ISSN
0160-6689 (ISSN-L)
OpenAlex
W1996472589
Cited by
54
References
11
Citations by year
2026: 3 · 2025: 2 · 2024: 4 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2015: 5 · 2014: 2 · 2013: 11 · 2012: 9
FWCI
5.23
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R29MH57511, R01MH057934, R29MH057511, R01MH-57934)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
adult ADHD, clinical trial representativeness, generalizability, inclusion and exclusion criteria, psychiatric comorbidity, functional disability, Global Assessment of Functioning, occupational status, socioeconomic status
MeSH terms
Adult, Attention Deficit Disorder with Hyperactivity, Clinical Trials as Topic, Cognition, Female, Humans, Male, Mental Health, Middle Aged, Occupations, Psychiatric Status Rating Scales, Residence Characteristics, Sampling Studies, Severity of Illness Index, Social Class, United States, Comorbidity, Selection Bias, Patient Selection, Observation, Diagnostic and Statistical Manual of Mental Disorders

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