Assay sensitivity and study features in neuropathic pain trials: An ACTTION meta-analysis
Open accessAbstract
OBJECTIVE: Our objective was to identify patient, study, and site factors associated with assay sensitivity in placebo-controlled neuropathic pain trials. METHODS: We examined the associations between study characteristics and standardized effect size (SES) in a database of 200 publicly available randomized clinical trials of pharmacologic treatments for neuropathic pain. RESULTS: There was considerable heterogeneity in the SESs among the examined trials. Univariate meta-regression analyses indicated that larger SESs were significantly associated with trials that had 1) greater minimum baseline pain inclusion criteria, 2) greater mean subject age, 3) a larger percentage of Caucasian subjects, and 4) a smaller total number of subjects. In a multiple meta-regression analysis, the associations between SES and minimum baseline pain inclusion criterion and age remained significant. CONCLUSIONS: Our analyses have examined potentially modifiable correlates of study SES and shown that a minimum pain inclusion criterion of 40 or above on a 0 to 100 scale is associated with a larger SES. These data provide a foundation for investigating strategies to improve assay sensitivity and thereby decrease the likelihood of falsely negative outcomes in clinical trials of efficacious treatments for neuropathic pain.
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.
Integrity signals
Registry
Cites
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.
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?
Heterogeneity of patient phenotypes in clinical trials may reflect various underlying mechanisms.
“Lastly, a largely debated issue concerns the heterogeneity of patient phenotypes in clinical trials, which may reflect various underlying mechanisms.55–57”
From Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis (2015) · cites this paper as [55]
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
Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series
(2008) · doi:10.1002/9780470712184 · Cited by 25,048 · see citing works
Assessing the quality of reports of randomized clinical trials: Is blinding necessary?
Jadad, A. R., Moore, R. A., Carroll, D., Jenkinson, C., Reynolds, D. J. M., Gavaghan, D. J., & McQuay, H. J. (1996) · Controlled Clinical Trials · doi:10.1016/0197-2456(95)00134-4 · Cited by 17,582 · see citing works
Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2009) · doi:10.1002/9780470743386 · Cited by 14,225 · see citing works
Zhang, Q., Wang, C., Zheng, M., Li, Y., Li, J., Zhang, L., Shang, X., & Yan, C. (2014) · Cerebrovascular Diseases · doi:10.1159/000369778 · Cited by 11,609 · see citing works
Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2021) · doi:10.1002/9781119558378 · Cited by 9,799 · see citing works
Dong, Y., Hao, L., Shi, Z., Wang, G., Zhang, Z., & Han, C. (2013) · Urologia Internationalis · doi:10.1159/000351405 · Cited by 4,556 · see citing works
Funnel plots for detecting bias in meta-analysis
Sterne, J. A. C., & Egger, M. (2001) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(01)00377-8 · Cited by 3,779 · see citing works
Pharmacologic management of neuropathic pain: Evidence-based recommendations
Dworkin, R. H., O’Connor, A. B., Backonja, M., Farrar, J. T., Finnerup, N. B., Jensen, T. S., Kalso, E. A., Loeser, J. D., Miaskowski, C., Nurmikko, T. J., et al. (2007) · Pain · doi:10.1016/j.pain.2007.08.033 · Cited by 2,126 · see citing works
Self-citationRobust variance estimation in meta‐regression with dependent effect size estimates
Hedges, L. V., Tipton, E., & Johnson, M. C. (2010) · Research Synthesis Methods · doi:10.1002/jrsm.5 · Cited by 2,086 · see citing works
EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision
Attal, N., Cruccu, G., Baron, R., Haanpää, M., Hansson, P., Jensen, T. S., & Nurmikko, T. (2010) · European Journal of Neurology · doi:10.1111/j.1468-1331.2010.02999.x · Cited by 1,873 · see citing works
Imputing missing standard deviations in meta-analyses can provide accurate results
Furukawa, T. A., Barbui, C., Cipriani, A., Brambilla, P., & Watanabe, N. (2006) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2005.06.006 · Cited by 1,568 · see citing works
International Conference on Harmonisation
Guy, R. C. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-386454-3.00861-7 · Cited by 1,487 · see citing works
NeuPSIG guidelines on neuropathic pain assessment
Haanpää, M., Attal, N., Backonja, M., Baron, R., Bennett, M., Bouhassira, D., Cruccu, G., Hansson, P., Haythornthwaite, J. A., Iannetti, G. D., et al. (2011) · Pain · doi:10.1016/j.pain.2010.07.031 · Cited by 1,060 · see citing works
Self-citationThe evidence for pharmacological treatment of neuropathic pain
Finnerup, N. B., Sindrup, S. H., & Jensen, T. S. (2010) · Pain · doi:10.1016/j.pain.2010.06.019 · Cited by 1,045 · see citing works
Meta‐Analysis Of Controlled Clinical Trials
Whitehead, A. (2002) · doi:10.1002/0470854200 · Cited by 827 · see citing works
Bril, V., England, J., Franklin, G. M., Backonja, M., Cohen, J., Del Toro, D., Feldman, E., Iverson, D. J., Perkins, B., Russell, J. W., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e3182166ebe · Cited by 634 · see citing works
Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study
Nuesch, E., Trelle, S., Reichenbach, S., Rutjes, A. W. S., Tschannen, B., Altman, D. G., Egger, M., & Juni, P. (2010) · BMJ · doi:10.1136/bmj.c3515 · Cited by 559 · see citing works
Berlin, J. A., Santanna, J., Schmid, C. H., Szczech, L. A. M., & Feldman, H. I. (2002) · Statistics in Medicine · doi:10.1002/sim.1023 · Cited by 468 · see citing works
Meta-analysis: Chondroitin for Osteoarthritis of the Knee or Hip
Reichenbach, S., Sterchi, R., Scherer, M., Trelle, S., Bürgi, E., Bürgi, U., Dieppe, P. A., & Jüni, P. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-146-8-200704170-00009 · Cited by 316 · see citing works
Practice Parameter: Treatment of postherpetic neuralgia: [RETIRED]
Dubinsky, R., Kabbani, H., Elchami, Z., Boutwell, C., & Ali, H. (2004) · Neurology · doi:10.1212/01.wnl.0000140708.62856.72 · Cited by 299 · see citing works
Dworkin, R. H., Turk, D. C., Peirce‐Sandner, S., Burke, L. B., Farrar, J. T., Gilron, I., Jensen, M. P., Katz, N. P., Raja, S. N., Rappaport, B. A., et al. (2012) · Pain · doi:10.1016/j.pain.2012.03.003 · Cited by 284 · see citing works
Self-citationGabapentin Is a First Line Drug for the Treatment of Neuropathic Pain in Spinal Cord Injury
Levendoğlu, F., Öğün, C. Ö., Özerbil, Ö. M., Öğün, T. C., & Uğurlu, H. (2004) · Spine · doi:10.1097/01.brs.0000112068.16108.3a · Cited by 266 · see citing works
A placebo-controlled trial of lamotrigine for painful HIV-associated neuropathy
Simpson, D. M., Olney, R. K., McArthur, J. C., Khan, A., Godbold, J., Ebel-Frommer, K., & for the Lamotrigine HIV Neuropathy Study Group (2000) · Neurology · doi:10.1212/wnl.54.11.2115 · Cited by 242 · see citing works
Tölle, T. R., Freynhagen, R., Versavel, M., Trostmann, U., & Young, J. P. (2007) · European Journal of Pain · doi:10.1016/j.ejpain.2007.05.003 · Cited by 219 · see citing works
Meta‐analysis combining parallel and cross‐over clinical trials. I: Continuous outcomes
Curtin, F., Altman, D. G., & Elbourne, D. R. (2002) · Statistics in Medicine · doi:10.1002/sim.1205 · Cited by 208 · see citing works
Clinical trial outcome in neuropathic pain
Katz, J., Finnerup, N. B., & Dworkin, R. H. (2007) · Neurology · doi:10.1212/01.wnl.0000275528.01263.6c · Cited by 167 · see citing works
Self-citationCharacterization and consequences of pain variability in individuals with fibromyalgia
Harris, R. E., Williams, D. A., McLean, S. A., Sen, A., Hufford, M. R., Gendreau, R. M., Gracely, R. H., & Clauw, D. J. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21407 · Cited by 152 · see citing works
Bafeta, A., Dechartres, A., Trinquart, L., Yavchitz, A., Boutron, I., & Ravaud, P. (2012) · BMJ · doi:10.1136/bmj.e813 · Cited by 129 · see citing works
Häuser, W., Bartram-Wunn, E., Bartram, C., Reinecke, H., & Tölle, T. R. (2011) · Pain · doi:10.1016/j.pain.2011.01.050 · Cited by 124 · see citing works
Placebo response in neuropathic pain trials ☆
Quessy, S. N., & Rowbotham, M. C. (2008) · Pain · doi:10.1016/j.pain.2008.06.024 · Cited by 102 · see citing works
Self-citationMethodological issues in clinical trials of opioids for chronic pain
Katz, N. P. (2005) · Neurology · doi:10.1212/wnl.65.12_suppl_4.s32 · Cited by 90 · see citing works
Self-citationZiegler, D., Pritchett, Y., Wang, F., Desaiah, D., Robinson, M. J., Hall, J. A., & Chappell, A. S. (2007) · Diabetes Care · doi:10.2337/dc06-2009 · Cited by 86 · see citing works
Evidence-based clinical trial design for chronic pain pharmacotherapy: A blueprint for ACTION
Dworkin, R. H., Turk, D. C., Katz, N. P., Rowbotham, M. C., Peirce‐Sandner, S., Cerny, I., Clingman, C. S., Eloff, B. C., Farrar, J. T., Kamp, C., et al. (2010) · Pain · doi:10.1016/j.pain.2010.11.008 · Cited by 83 · see citing works
Self-citationDworkin, R. H., Peirce‐Sandner, S., Turk, D., McDermott, M., Gibofsky, A., Simon, L. S., Farrar, J. T., & Katz, N. P. (2011) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2011.02.020 · Cited by 52 · see citing works
Self-citationPredictors of Placebo Response in Pooled Lamotrigine Neuropathic Pain Clinical Trials
Irizarry, M. C., Webb, D. J., Ali, Z., Chizh, B. A., Gold, M., Kinrade, F., Meisner, P. D., Blum, D., Silver, M. T., & Weil, J. (2009) · Clinical Journal of Pain · doi:10.1097/ajp.0b013e31819ddded · Cited by 48 · see citing works
Dworkin, R. H., Turk, D. C., Peirce‐Sandner, S., McDermott, M., Farrar, J. T., Hertz, S. H., Katz, N. P., Raja, S. N., & Rappaport, B. A. (2010) · Pain · doi:10.1016/j.pain.2010.02.002 · Cited by 38 · see citing works
Self-citationACTION on the Prevention of Chronic Pain after Surgery
Rappaport, B. A., Cerny, I., & Sanhai, W. R. (2010) · Anesthesiology · doi:10.1097/aln.0b013e3181cf4279 · Cited by 23 · see citing works
Self-citationThe case for publishing ‘negative’ clinical trials
Rowbotham, M. C. (2009) · Pain · doi:10.1016/j.pain.2009.09.026 · Cited by 19 · see citing works
Self-citationA snapshot and scorecard for analgesic clinical trials for chronic pain: The RReACT database
Greene, K. A., Dworkin, R. H., & Rowbotham, M. C. (2012) · Pain · doi:10.1016/j.pain.2012.06.004 · Cited by 11 · see citing works
Self-citationMeta-analysis: formulating, evaluating, combining, and reporting
Normand, S.-L. T. (1999) · Statistics in Medicine · doi:10.1002/(sici)1097-0258(19990215)18:3
Flagged first, then by citations
Research works printed but not linked: 2
- Dubinsky RM, Kabbani H, El-Chami Z, Boutwell C, Ali H. Practice parameter: treatment of postherpetic neu- ralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2004;63:959-965.
- Higgins JPT, Green S. Cochrane Handbook for System- atic Reviews of Interventions. Chichester: John Wiley & Sons; 2008.
Cited by
Sorted by citations
Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis
Finnerup, N. B., Attal, N., Haroutounian, S., McNicol, E., Baron, R., Dworkin, R. H., Gilron, I., Haanpää, M., Hansson, P., Jensen, T. S., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70251-0 · Cited by 3,980 · see citing works
Self-citationPatient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations
Edwards, R. R., Dworkin, R. H., Turk, D. C., Angst, M. S., Dionne, R., Freeman, R., Hansson, P., Haroutounian, S., Arendt-Nielsen, L., Attal, N., et al. (2016) · Pain · doi:10.1097/j.pain.0000000000000602 · Cited by 403 · see citing works
Self-citationInterpretation of chronic pain clinical trial outcomes: IMMPACT recommended considerations
Smith, S. M., Dworkin, R. H., Turk, D. C., McDermott, M. P., Eccleston, C., Farrar, J. T., Rowbotham, M. C., Bhagwagar, Z., Burke, L. B., Cowan, P., et al. (2020) · Pain · doi:10.1097/j.pain.0000000000001952 · Cited by 194 · see citing works
Self-citation
- Authors
- Dworkin, R. H., Turk, D. C., Peirce-Sandner, S., He, H., McDermott, M. P., Farrar, J. T., Katz, N. P., Lin, A. H., Rappaport, B. A., & Rowbotham, M. C.
- Affiliations
- Tufts University (US)
- From the Departments of Anesthesiology (R.H.D., S.P.-S.), Biostatistics and Computational Biology (H.H., M.P.M.), and Neurology (R.H.D., M.P.M), University of Rochester School of Medicine and Dentistry, Rochester, NY; Department of Anesthesiology and Pain Medicine (D.C.T.), University of Washington, Seattle; Department of Clinical Epidemiology and Biostatistics (J.T.F.), University of Pennsylvania, Philadelphia; Analgesic Solutions, Natick, and Tufts University, Boston (N.P.K.), MA; Division of...
- Venue
- Neurology
- Published
- 2013-07-02
- Volume
- 81
- Issue
- 1
- Pages
- 67-75
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3770199
- OpenAlex
- W2013578490
- Cited by
- 38
- References
- 41
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 5
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Food and Drug Administration (U01 FD004187)
- U.S. Public Health Service (HHSF 223201000078C)
- National Institute on Aging (U01AG030644)
- National Institute on Drug Abuse (R01DA032776, R01DA026887)
- National Cancer Institute (R01CA158243)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR064153, R01AR059102)
- National Center for Research Resources (TL1RR024133)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Keywords
- neuropathic pain, assay sensitivity, standardized effect size, trial characteristics, racial composition, sample size, pharmacotherapy
- MeSH terms
- Age Factors, Clinical Trials as Topic, Humans, Neuralgia, Research Design, Sensitivity and Specificity, Treatment Outcome
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
