Adverse event reporting in surgical trials and early phase studies: the need for new and joint perspectives
We support the consensus recommendations from Lineberry et al to improve credibility and transparency in publications of industry-sponsored research on informative and clinical relevant adverse event reporting(1).
We also support a similar thorough, joint and transparent process for the development of standards and consensus for reporting of benefit and harm outcomes in surgical trials, including early phase surgical studies. Recent reviews have summarised heterogeneity of outcome reporting in many surgical areas(2-6), including in the evaluation of innovative surgical procedures(7). This limits evidence syntheses and risks outcome reporting bias. For early phase studies, the reporting of selective outcomes is likely to lead to over-optimistic assessment of new interventions and under-reporting of adverse effects. Without systematic and transparent evaluation, with details reported as recommended by Lineberry et al (e.g. numerators and denominators for all events), surgeons continue to innovate without reliable information about adverse effects. This means that the true extent of harm to patients from undergoing evolving surgical techniques is uncertain and often only becomes apparent once National Registries summarise outcomes (3,8). Such disasters could potentially be minimised by the routine measurement and reporting of adverse events in early phase surgical studies.
There is an urgent need for surgeons to work with industry, the National Office for Clinical Research Infrastructure and professional bodies to develop agreed minimal mandated sets of benefit and harm outcomes to measure within each phase of surgical innovation; from evolving through to stabilised and adopted interventions. Methodology developed with the COMET initiative (www.comet-initiative.org/) now enables the identification and categorisation of benefit and harm outcomes in early phase surgical studies and the development, via consensus methods, of minimal mandated sets of benefit and harm outcomes. The recent NIHR Biomedical Research Centre award to Bristol University includes work to develop such sets, with the potential to expedite the swift rejection of unsafe or ineffective techniques and promote the efficient development of promising innovations.
Kerry N L Avery 1, Sara T Brookes 1, Hollie Richards 1, Shelley Potter 1,2, Ashley Blom 1, Rob Hinchliffe 1,3, Jane M Blazeby 1,4 on behalf of the NIHR Biomedical Research Centre Surgical Innovation Theme 1
1 University of Bristol, Bristol, UK
2 Royal Liverpool and Broadgreen University Hospitals NHS Trust
3 North Bristol NHS Trust, UK
4 University Hospitals Bristol NHS Foundation Trust, Bristol, UK
1. Lineberry N, Berlin JA, Mansi B, Glasser S, Berkwits M, Klem C et al. Recommendations to improve adverse event reporting in clinical trial publications: a joint pharmaceutical industry/journal editor perspective. BMJ 2016;355:i5078.
2. Hopkins JC, Howes N, Chalmers K, Savovic J, Whale K, Coulman KD, Welbourn R, Whistance RN, Andrews RC, Byrne JP, Mahon D, Blazeby JM; By-Band Trial Management Group Outcome reporting in bariatric surgery: an in-depth analysis to inform the development of a core outcome set, the BARIACT Study. Obes Rev. 2015 Jan;16(1):88-106. doi: 10.1111/obr.12240. Epub 2014 Nov 30. PMID: 25442513
3. Potter S, Browning D, Savović J, Holcombe C, Blazeby JM. Systematic review and critical appraisal of the impact of acellular dermal matrix use on the outcomes of implant-based breast reconstruction. Br J Surg 2015;102:1010-25.
4. Blencowe NS, McNair AG, Davis CR, Brookes ST, Blazeby JM. Standards of outcome reporting in surgical oncology: a case study in esophageal cancer. Ann Surg Oncol 2012;19:4012-8
5. Whistance RN, Forsythe RO, McNair AG, Brookes ST, Avery KN, Pullyblank AM et al. A systematic review of outcome reporting in colorectal cancer surgery. Colorectal Dis 2013;15:e548-60.
6. Bhangu A, Singh P, Pinkney T, Blazeby JM. A detailed analysis of outcome reporting from randomised controlled trials and meta-analyses of inguinal hernia repair. Hernia 2015;19:65-75.
7. Currie A, Brigic A, Blencowe NS, Potter S, Faiz OD, Kennedy RH, Blazeby JM. Systematic review of surgical innovation reporting in laparoendoscopic colonic polyp resection. Br J Surg 2015;102:e108-16.
8. Smith AJ, Dieppe P, Vernon K, Porter M, Blom AW, National Joint Registry of England and Wales. Failure rates of stemmed metal-on-metal hip replacements: analysis of data from The National Joint Registry of England and Wales. Lancet 2012;379:1199-204.
Competing interests: No competing interests