Advertisement

Adverse Event Reporting in Clinical Trials of Intravenous and Invasive Pain Treatments: An ACTTION Systematic Review

Published:August 11, 2016DOI:https://doi.org/10.1016/j.jpain.2016.07.006

      Highlights

      • Only 5 of 10 Consolidated Standards of Reporting Trials harms recommendations were fulfilled on average.
      • Adverse event (AE) assessments, number of AEs, and denominators were well reported.
      • The specific AEs evaluated and withdrawals due to AEs were less well reported.
      • Little improvement in AE reporting occurred between 2000 to 2003 and 2008 to 2012.
      • 8% of the reviewed articles failed to report any information on AEs.

      Abstract

      Thorough assessment and reporting of adverse events (AEs) facilitates a detailed understanding of a treatment's risk–benefit profile. Although the Consolidated Standards of Reporting Trials (CONSORT) 2004 statement provides recommendations regarding AE reporting, adherence to these standards is often inadequate. We investigated AE reporting in clinical trials of intravenous and invasive pain treatments published in 6 major anesthesiology and pain journals between 2000 to 2003 and 2006 to 2012. We examined whether AE reporting improved after publication of the 2004 CONSORT recommendations and also comprehensively reviewed AE assessment using the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) AE reporting recommendations. No improvement was found overall in CONSORT harms reporting scores from pre- to postpublication of the CONSORT recommendations, with only 5 of 10 fulfilled on average. AE reporting assessed using the ACTTION coding manual was generally inadequate, and 8% of articles failed to report any AE information at all. Anesthesiology and pain journals were similar in AE reporting quality, although industry-sponsored trials reported more AE information than nonindustry sponsored trials. Improvement is needed in AE reporting in analgesic clinical trials. The CONSORT checklist and ACTTION AE recommendations can assist investigators and editors in improving clinical trial transparency and quality.

      Perspective

      This systematic review of AE reporting in intravenous and invasive pain treatment trials shows that little improvement has been made since the 2004 CONSORT harms reporting guidelines. Better assessment and reporting of treatment AEs is necessary to understand the full clinical effect of intravenous and invasive treatments.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Basch E.
        The missing voice of patients in drug-safety reporting.
        N Engl J Med. 2010; 362: 865-869
        • Bates D.W.
        • Spell N.
        • Cullen D.J.
        • Burdick E.
        • Laird N.
        • Petersen L.A.
        • Small S.D.
        • Sweitzer B.J.
        • Leape L.L.
        The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group.
        JAMA. 1997; 277: 307-311
        • Begg C.
        • Cho M.
        • Eastwood S.
        • Horton R.
        • Moher D.
        • Olkin I.
        • Pitkin R.
        • Rennie D.
        • Schulz K.F.
        • Simel D.
        • Stroup D.F.
        Improving the quality of reporting of randomized controlled trials. The CONSORT statement.
        JAMA. 1996; 276: 637-639
        • Bent S.
        • Padula A.
        • Avins A.L.
        Brief communication: Better ways to question patients about adverse medical events: A randomized, controlled trial.
        Ann Intern Med. 2006; 144: 257-261
        • Chowers M.Y.
        • Gottesman B.S.
        • Leibovici L.
        • Pielmeier U.
        • Andreassen S.
        • Paul M.
        Reporting of adverse events in randomized controlled trials of highly active antiretroviral therapy: Systematic review.
        J Antimicrob Chemother. 2009; 64: 239-250
        • Classen D.C.
        • Pestotnik S.L.
        • Evans R.S.
        • Lloyd J.F.
        • Burke J.P.
        Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality.
        JAMA. 1997; 277: 301-306
        • Cooper J.B.
        • Gaba D.
        No myth: Anesthesia is a model for addressing patient safety.
        Anesthesiology. 2002; 97: 1335-1337
        • Cornelius V.R.
        • Sauzet O.
        • Williams J.E.
        • Ayis S.
        • Farquhar-Smith P.
        • Ross J.R.
        • Branford R.A.
        • Peacock J.L.
        Adverse event reporting in randomised controlled trials of neuropathic pain: Considerations for future practice.
        Pain. 2013; 154: 213-220
        • de Vries T.W.
        • van Roon E.N.
        Low quality of reporting adverse drug reactions in paediatric randomised controlled trials.
        Arch Dis Child. 2010; 95: 1023-1026
        • Dixon Jr,
        The International Conference on Harmonization Good Clinical Practice guideline.
        Qual Assur. 1998; 6: 65-74
        • Dworkin R.H.
        • Turk D.C.
        • Peirce-Sandner S.
        • Baron R.
        • Bellamy N.
        • Burke L.B.
        • Chappell A.
        • Chartier K.
        • Cleeland C.S.
        • Costello A.
        • Cowan P.
        • Dimitrova R.
        • Ellenberg S.
        • Farrar J.T.
        • French J.A.
        • Gilron I.
        • Hertz S.
        • Jadad A.R.
        • Jay G.W.
        • Kalliomaki J.
        • Katz N.P.
        • Kerns R.D.
        • Manning D.C.
        • McDermott M.P.
        • McGrath P.J.
        • Narayana A.
        • Porter L.
        • Quessy S.
        • Rappaport B.A.
        • Rauschkolb C.
        • Reeve B.B.
        • Rhodes T.
        • Sampaio C.
        • Simpson D.M.
        • Stauffer J.W.
        • Stucki G.
        • Tobias J.
        • White R.E.
        • Witter J.
        Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations.
        Pain. 2010; 149: 177-193
        • Edwards J.E.
        • McQuay H.J.
        • Moore R.A.
        • Collins S.L.
        Reporting of adverse effects in clinical trials should be improved: Lessons from acute postoperative pain.
        J Pain Symptom Manage. 1999; 18: 427-437
        • Freeman M.
        • Tukey J.
        Transformations related to the angular and the square root.
        Ann Math Stat. 1950; 21: 607-611
        • Gaba D.M.
        Anaesthesiology as a model for patient safety in health care.
        BMJ. 2000; 320: 785-788
        • Gandhi T.K.
        • Weingart S.N.
        • Borus J.
        • Seger A.C.
        • Peterson J.
        • Burdick E.
        • Seger D.L.
        • Shu K.
        • Federico F.
        • Leape L.L.
        • Bates D.W.
        Adverse drug events in ambulatory care.
        N Engl J Med. 2003; 348: 1556-1564
        • Haidich A.B.
        • Birtsou C.
        • Dardavessis T.
        • Tirodimos I.
        • Arvanitidou M.
        The quality of safety reporting in trials is still suboptimal: Survey of major general medical journals.
        J Clin Epidemiol. 2011; 64: 124-135
        • Hunsinger M.
        • Smith S.M.
        • Rothstein D.
        • McKeown A.
        • Parkhurst M.
        • Hertz S.
        • Katz N.P.
        • Lin A.H.
        • McDermott M.P.
        • Rappaport B.A.
        • Turk D.C.
        • Dworkin R.H.
        Adverse event reporting in nonpharmacologic, noninterventional pain clinical trials: ACTTION systematic review.
        Pain. 2014; 155: 2253-2262
        • Ioannidis J.P.
        • Evans S.J.
        • Gotzsche P.C.
        • O’Neill R.T.
        • Altman D.G.
        • Schulz K.
        • Moher D.
        • CONSORT Group
        Better reporting of harms in randomized trials: An extension of the CONSORT statement.
        Ann Intern Med. 2004; 141: 781-788
        • Ioannidis J.P.
        • Mulrow C.D.
        • Goodman S.N.
        Adverse events: The more you search, the more you find.
        Ann Intern Med. 2006; 144: 298-300
        • Lazarou J.
        • Pomeranz B.H.
        • Corey P.N.
        Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies.
        JAMA. 1998; 279: 1200-1205
        • Moher D.
        • Schulz K.F.
        • Altman D.
        • CONSORT Group (Consolidated Standards of Reporting Trials)
        The CONSORT statement: Revised recommendations for improving the quality of reports of parallel-group randomized trials.
        JAMA. 2001; 285: 1987-1991
        • O’Connor A.B.
        Neuropathic pain: Quality-of-life impact, costs and cost effectiveness of therapy.
        Pharmacoeconomics. 2009; 27: 95-112
        • Pitrou I.
        • Boutron I.
        • Ahmad N.
        • Ravaud P.
        Reporting of safety results in published reports of randomized controlled trials.
        Arch Intern Med. 2009; 169: 1756-1761
        • Rief W.
        • Nestoriuc Y.
        • von Lilienfeld-Toal A.
        • Dogan I.
        • Schreiber F.
        • Hofmann S.G.
        • Barsky A.J.
        • Avorn J.
        Differences in adverse effect reporting in placebo groups in SSRI and tricyclic antidepressant trials: A systematic review and meta-analysis.
        Drug Saf. 2009; 32: 1041-1056
        • Smith S.M.
        • Chang R.D.
        • Pereira A.
        • Shah N.
        • Gilron I.
        • Katz N.P.
        • Lin A.H.
        • McDermott M.P.
        • Rappaport B.A.
        • Rowbotham M.C.
        • Sampaio C.
        • Turk D.C.
        • Dworkin R.H.
        Adherence to CONSORT harms-reporting recommendations in publications of recent analgesic clinical trials: An ACTTION systematic review.
        Pain. 2012; 153: 2415-2421
        • Smith S.M.
        • Wang A.T.
        • Katz N.P.
        • McDermott M.P.
        • Burke L.B.
        • Coplan P.
        • Gilron I.
        • Hertz S.H.
        • Lin A.H.
        • Rappaport B.A.
        • Rowbotham M.C.
        • Sampaio C.
        • Sweeney M.
        • Turk D.C.
        • Dworkin R.H.
        Adverse event assessment, analysis, and reporting in recent published analgesic clinical trials: ACTTION systematic review and recommendations.
        Pain. 2013; 154: 997-1008
        • Tugwell P.
        • Judd M.G.
        • Fries J.F.
        • Singh G.
        • Wells G.A.
        Powering our way to the elusive side effect: A composite outcome ‘basket’ of predefined designated endpoints in each organ system should be included in all controlled trials.
        J Clin Epidemiol. 2005; 58: 785-790
        • Turk D.C.
        • Dworkin R.H.
        • Allen R.R.
        • Bellamy N.
        • Brandenburg N.
        • Carr D.B.
        • Cleeland C.
        • Dionne R.
        • Farrar J.T.
        • Galer B.S.
        • Hewitt D.J.
        • Jadad A.R.
        • Katz N.P.
        • Kramer L.D.
        • Manning D.C.
        • McCormick C.G.
        • McDermott M.P.
        • McGrath P.
        • Quessy S.
        • Rappaport B.A.
        • Robinson J.P.
        • Royal M.A.
        • Simon L.
        • Stauffer J.W.
        • Stein W.
        • Tollett J.
        • Witter J.
        Core outcome domains for chronic pain clinical trials: IMMPACT recommendations.
        Pain. 2003; 106: 337-345
        • Turner L.A.
        • Singh K.
        • Garritty C.
        • Tsertsvadze A.
        • Manheimer E.
        • Wieland L.S.
        • Galipeau J.
        • Moher D.
        An evaluation of the completeness of safety reporting in reports of complementary and alternative medicine trials.
        BMC Complement Altern Med. 2011; 11: 67