Development of a core outcome set for clinical trials in inflammatory bowel disease: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey.

Introduction: Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel disease (IBD), are chronic, progressive and disabling disorders of the gastrointestinal tract. Although data from randomised controlled trials (RCTs) provide the foundation of evidence that validates medical therapy for IBD, considerable heterogeneity exists in the measured outcomes used in these studies. Furthermore, in recent years, there has been a paradigm shift in IBD treatment targets, moving from symptom-based scoring to improvement or normalisation of objective measures of inflammation such as endoscopic appearance, inflammatory biomarkers and histological and radiographic end points. The abundance of new treatment options and evolving end points poses opportunities and challenges for all stakeholders involved in drug development. Accordingly, there exists a need to harmonise measures used in clinical trials through the development of a core outcome set (COS).
Methods and Analysis: The development of an IBD-specific COS includes four steps. First, a systematic literature review is performed to identify outcomes previously used in IBD RCTs. Second, semistructured qualitative interviews are conducted with key stakeholders, including patients, clinicians, researchers, pharmaceutical industry representatives, healthcare payers and regulators to identify additional outcomes of importance. Using the outcomes generated from literature review and stakeholder interviews, an international two-round Delphi survey is conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting is held to ratify the COS and disseminate findings for application in future IBD trials.
Ethics and Dissemination: Given that over 30 novel therapeutic compounds are in development for IBD treatment, the design of robust clinical trials measuring relevant and standardised outcomes is crucial. Standardising outcomes through a COS will reduce heterogeneity in trial reporting, facilitate valid comparisons of new therapies and improve clinical trial quality.
Competing Interests: Competing interests: CM has no conflicts of interest to declare. RP has received scientific advisory board fees from Abbott/AbbVie, Amgen, Janssen, Merck, Pfizer, Prometheus Laboratories, Salix Pharma, Shire, Takeda, WarnerChilcott; consulting fees from Abbott/AbbVie, Amgen, Aptalis, Astra Zeneca,Baxter, BMS, Centocor, Elan/Biogen, Eisai, Ferring, GSK, Janssen, Merck,Millennium, Pfizer, Proctor & Gamble, Prometheus Therapeutics andDiagnostics, Schering-Plough, Shire, Takeda, UCB Pharma, Warner Chilcott;research grants from Abbott/AbbVie, Amgen, Aptalis, Astra Zeneca, Baxter, BMS,Centocor, Eisai, Elan/Biogen, Ferring, GSK, Janssen, Merck, Millennium, Pfizer,Proctor & Gamble, Prometheus, Shire, Schering-Plough, Takeda, UCB Pharma,Warner Chilcott; and 495 speaker’s bureau fees from Abbott/AbbVie, Amgen, Aptalis, Astra Zeneca, Baxter, BMS, Centocor, Eisai, Elan/Biogen, Ferring, GSK, Janssen, Merck, Millennium, Pfizer, Proctor & Gamble, Prometheus, Schering-Plough, Shire, Takeda, UCB Pharma, Warner Chilcott. RF has received scientific advisory board fees from Abbott/AbbVie, Celltrion, Ferring, Janssen, Shire, VSL#3; consulting fees from Abbott/AbbVie, Celltrion, Ferring, Janssen, Shire, VSL#3; and research grant support from Abbott/AbbVie, Alba Therapeutics, BMS, Celltrion, Centocor, Genentech, GSK, Janssen, Merck, Millennium, Novartis, Pfizer, Proctor & Gamble, Roche, VSL#3. CP has no conflicts of interest todeclare. RK has received consulting fees from AbbVie, Takeda, and Janssen. BL has received consulting fees from AbbVie, Takeda, Nestle Health Sciences, and Prometheus Labs. WS has served as a consultant to AbbVie Inc., ActoGeniX NV,AGI Therapeutics, Inc, Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas Pharma, Athersys, Inc, AtlanticHealthcare Limited, Axcan Pharma (now Aptalis), BioBalance Corporation,Boehringer-Ingelheim Inc, Bristol Meyers Squibb, Celgene, CelekPharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis,Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, EaglePharmaceuticals, Eisai Medical Research Inc, Elan Pharmaceuticals, EnGene, Inc,Eli Lilly, Enteromedics, Exagen Diagnostics, Inc, Ferring Pharmaceuticals,Flexion Therapeutics, Inc, Funxional Therapeutics Limited, Genzyme Corporation, Genentech (now Roche), Gilead Sciences, Given Imaging, Glaxo Smith Kline, HumanGenome Sciences, Ironwood Pharmaceuticals (previously Microbia Inc), Janssen(previously Centocor), KaloBios Pharmaceuticals, Inc, Lexicon Pharmaceuticals,Lycera Corporation, Meda Pharmaceuticals (previously Alaven Pharmaceuticals), Merck Research Laboratories, MerckSerono, Millennium Pharmaceuticals(subsequently merged with Takeda), Nisshin Kyorin Pharmaceuticals Co, Ltd, NovoNordisk A/S, NPS Pharmaceuticals, Optimer Pharmaceuticals, OrexigenTherapeutics, Inc, PDL Biopharma, Pfizer, Procter and Gamble, PrometheusLaboratories, ProtAb Limited, Purgenesis Technologies, Inc, Receptos, Relypsa,Inc, Salient Pharmaceuticals, Salix Pharmaceuticals, Inc, Santarus, ScheringPlough Corporation (acquired by Merck), Shire Pharmaceuticals, Sigmoid PharmaLimited, Sirtris Pharmaceuticals, Inc (a GSK company), SLA Pharma (UK) Limited,Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG (acquired by Zeria Pharmaceutical Co, Ltd), TxCell SA, UCB Pharma, Viamet Pharmaceuticals,Vascular Biogenics Limited (VBL), Warner Chilcott UK Limited; has receivedspeaker’s fees from AbbVie Inc, Bristol Meyers Squibb and Janssen (previously Centocor); and financial support for research from AbbVie Inc, Bristol Meyers Squibb, Genentech, Glaxo Smith Kline, Janssen (previously Centocor), Millennium Pharmaceuticals (now Takeda), Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire Pharmaceuticals and UCB Pharma. Brian Feagan hasreceived grant/research support from Millennium Pharmaceuticals, Merck,Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc, Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix and Wyeth Pharmaceuticals Inc; consulting fees from Millennium Pharmaceuticals, Merck, Centocor Inc, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-MyersSquibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, TillottsPharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc, Salix Pharmaceuticals, Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc and Sigmoid Pharma; and speakers bureau fees from UCB, AbbVie and J&J/Janssen. VJ has received scientific advisory board feesfrom AbbVie, Sandoz, Takeda, Janssen; speakers fees from Takeda, Janssen,Shire, Ferring.
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