CoChat
Sign Up
Cited by 109Pharmacovigilance and Adverse Drug ReactionsPharmaceutical industry and healthcareStatistical Methods in Clinical Trials

Harms are assessed inconsistently and reported inadequately Part 2: nonsystematic adverse events

Open access
Mayo-Wilson, Evan, Fusco, Nicole, Li, Tianjing, Hong, Hwanhee, Canner, Joseph K., Dickersin, Kay, Bertizzolo, Lorenzo, Cowley, Terrie +14 more·2019·Journal of Clinical Epidemiology
DOI 10.1016/j.jclinepi.2019.04.020
Open this paper in CoChat — free account

Abstract

Objective We examined nonsystematic adverse events (AEs) in Part 2 (of 2) of a study describing the assessment and reporting AEs in clinical trials. Study Design and Setting We examined 21 trials of gabapentin for neuropathic pain (52 sources) and seven trials of quetiapine for bipolar depression (80 sources) using data from the Multiple Data Sources study. We extracted and compared information about nonsystematic AEs (i.e., AEs that were not assessed for every participant), including AEs categorized as "serious." We recorded whether AEs were grouped by anatomic or physiological system. Results Trials of the same drug reported information about different AEs. Information in public sources was inadequate for decision-making. No public source reported all AEs, or all serious AEs, identified in nonpublic sources about the same trial. Of trials with only public sources, 2/15 (13%) gabapentin and 0/3 (0%) quetiapine trials grouped AEs by anatomic or physiological system. Conclusion Public sources contained little information about nonsystematic AEs, including serious AEs. Grouping might make nonsystematic AEs easier to detect; however, most public sources did not report grouped AEs. Standards are needed to improve the collection and reporting of nonsystematic AEs so that stakeholders can use trials to assess the balance of potential benefits and harms.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.jclinepi.2019.04.020

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Specifying the methods of assessing, grouping, and analysing harms in the protocol helps to identify and deter the selective reporting of results in publications and registries.

    “Specifying the methods of assessing, grouping, and analysing harms in the protocol helps to identify and deter the selective reporting of results in publications and registries.280 281”

    From SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials (2025) · cites this paper as [281]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 12

  1. [25][25] International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. In: Introductory guide MedDRA version 17.0. Available at https://www.meddra.org/ sites/default/files/guidance/file/intguide\_17\_0\_english.pdf. Accessed May 12, 2018. -
  2. [30][30] International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. In: ICH 19. harmonised tripartite guideline: structure and content of clinical study reports E3. Available at http://www.ich.org/products/guidelines/ efficacy/efficacy-single/article/structure-and-content-of-clinical-studyreports.html. Accessed May 12, 2018. -
  3. [32][32] [Parke-Davis. Research report: 720-03908. A double-blind placebocontrolled trial of gabapentin for treatment of painful diabetic peripheral neuropathy 1998: Protocol Number: 945-210.](http://refhub.elsevier.com/S0895-4356(18)31109-0/sref32) -
  4. [33][33] [Parke-Davis. Research report: 995-00070. Double-blind, randomized, placebo-controlled, parallel groups, multi-center trial to determine the efficacy and safety of Neurontin (gabapentin) in subjects with peripheral neuropathy (post-herpetic neuralgia) 1998: Protocol Number: 945-211.](http://refhub.elsevier.com/S0895-4356(18)31109-0/sref33) -
  5. [34][34] [Parke-Davis. Research report: 720-04130. A double-blind placebocontrolled trial with 3 doses of gabapentin for treatment of painful diabetic neuropathy 2000: Protocol Number: 945-224.](http://refhub.elsevier.com/S0895-4356(18)31109-0/sref34) -
  6. [35][35] [Parke-Davis. Research report: 430-00125. A double blind placebo controlled trial of gabapentin for the treatment of patients exhibiting symptoms of neuropathic pain 2000: Protocol Number: 945-430-306 (NN 026).](http://refhub.elsevier.com/S0895-4356(18)31109-0/sref35) -
  7. [36][36] [Parke-Davis. Research report: 430-00124. A double-blind placebo controlled trial of gabapentin for the treatment of post herpetic neuralgia 2000: Protocol Number: 945-430-295 (NN 025).](http://refhub.elsevier.com/S0895-4356(18)31109-0/sref36) -
  8. [37][37] [Pfizer. Final study report: A 15 week randomized, double-blind, placebo controlled, parallel-group, multicenter study of Neurontin (gabapentin) for efficacy and quality of life in patients with painful diabetic peripheral neuropahty 2005: Protocol A945-1008.](http://refhub.elsevier.com/S0895-4356(18)31109-0/sref37) -
  9. [38][38] [AstraZeneca. A multicenter, double-blind, randomized, placebocontrolled, double- dummy trial of the use of quetiapine fumarate (SEROQUEL[Registered]) in the treatment of patients with bipolar depression 2005: Study code: 5077US/0049.](http://refhub.elsevier.com/S0895-4356(18)31109-0/sref38) -
  10. [39][39] [AstraZeneca. A confirmatory multicenter, double-blind, randomized, placebo-controlled study of the use of quetiapine fumarate (SEROQUEL) in the treatment of patients with bipolar depression [D1447C00135] 2005.](http://refhub.elsevier.com/S0895-4356(18)31109-0/sref39) -
  11. [40][40] [ABBYY. FineReader.. 11th ed. Milpitas, CA: ABBYY; 2011.](http://refhub.elsevier.com/S0895-4356(18)31109-0/sref40) -
  12. [45][45] [Mayo-Wilson E, Fusco N, Li T, Hong H, Canner JK, Dickersin K. Opportunities for selective reporting of non-systematic adverse events in randomized controlled trials: an observational study 2018: Submitted.](http://refhub.elsevier.com/S0895-4356(18)31109-0/sref45) -

Cited by

Sorted by citations

Related

Authors
Mayo-Wilson, E., Fusco, N., Li, T., Hong, H., Canner, J. K., Dickersin, K., Bertizzolo, L., Cowley, T., Doshi, P., Ehmsen, J., Gresham, G., Guo, N., Haythornthwaite, J., Heyward, J., Pham, D., Payne, J., Rosman, L., Stuart, E., Suarez-Cuervo, C., Tolbert, E., Twose, C., & Vedula, S.
Affiliations
Johns Hopkins University (US)
ORCID
Venue
Journal of Clinical Epidemiology
Publisher
Elsevier BV
Published
2019-09
Volume
113
Pages
11-19
ISSN
0895-4356 (ISSN-L)
DOI
10.1016/j.jclinepi.2019.04.020
OpenAlex
W4229830654
Cited by
109
References
30
Citations by year
2026: 5 · 2025: 15 · 2024: 27 · 2023: 5 · 2022: 40 · 2021: 9 · 2020: 4 · 2019: 4
FWCI
10.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Epidemiology (publishedVersion, cc-by-nc-nd)
  • Pure Amsterdam UMC (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • IUScholarWorks Open (Indiana University) (submittedVersion)
Funders
Patient-Centered Outcomes Research Institute
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmaceutical industry and healthcare
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Keywords
serious adverse events, clinical trial reporting, gabapentin, neuropathic pain, quetiapine, bipolar depression, benefit-harm balance

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review