Report on the 6th ClinCom Workshop at ECCO’18
John Mansfield, ClinCom Member
The 6th ClinCom Workshop focussed on two current themes in IBD research: Evolving endpoints in clinical trials and comparative effectiveness research (CER).
Laurent Peyrin-Biroulet (Nancy, France) described the drivers that have led to the move from Crohn’s Disease Activity Index (CDAI) and Mayo scores to patient-reported outcomes (PROs) that just record clinical symptoms. The ultimate therapeutic goal is not only to reduce symptoms but also to return the patient to a normal life without disability. For Ulcerative Colitis (UC) the PRO uses rectal bleeding and stool frequency scores from the Mayo score, while for Crohn’s Disease (CD) abdominal pain and stool frequency scores are used. Many clinical trials also aim to show resolution of mucosal inflammation so endoscopic scores are frequently being used as co-primary endpoints with symptom scores. Some problems with PROs remain to be settled, especially the cut-off values for active disease, response and remission, and also the variability of patients’ assessment of loose stools and rectal bleeding.
Krisztina Gecse (Amsterdam, the Netherlands) then discussed the difficulties of defining endoscopic endpoints in Inflammatory Bowel Disease (IBD) trials. For CD the complexity of the Crohn’s Disease Endoscopic Index of Severity (CDEIS) has been reduced by using the Simple Endoscopic Score (SES-CD), in which each segment of the colonoscopically accessible bowel is scored for the affected area, the ulcerated area, the ulcer size and the presence of narrowings. A reduction in an individual CDEIS or SES-CD score of 50% is considered a response; however, remission is less clearly defined. The Rutgeerts score for postoperative recurrence remains the best-defined score in this sub-group of patients, although no formal validation is available. In UC there has been an evolution of endoscopic scoring from the Baron score through the Rachmilewitz score and Mayo score to the UCEIS. The UCEIS assesses vascular pattern, bleeding, the presence of erosions and ulcers but not mucosal friability, which is less reproducible.
|6th ClinCom Workshop at ECCO'18, Vienna © ECCO
Andrea Laghi (Rome, Italy) reviewed the role of cross-sectional imaging in disease assessment and trial endpoints. Of the five scores that have been described, the MaRIA score is most widely used. This score quantifies the magnetic resonance images in respect of the bowel wall thickness, contrast ratio, oedema and ulceration for each bowel segment. As originally described, the MaRIA score involves colonic distension, but patients often find this unacceptable, so a version that scores the small bowel alone is sometimes used.
Roger Feakins (London, UK) from H-ECCO reviewed the possibility of using histology scores as an endpoint in trials. He made the important point that not all the histological features of IBD are going to resolve with a decrease in inflammation, so a useful histological index would need to score the features of histological activity, such as cryptitis and crypt abscesses, rather than the features of chronic inflammation, such as basal plasmacytosis. Histological features, and therefore indices, take time to change, and the required time may differ for individual drugs and patients.
Walter Reinisch (Vienna, Austria) brought the session to a close with an excellent review of the clinical trial designs used in recent large IBD trials.
|6th ClinCom Workshop at ECCO'18, Vienna © ECCO
The second session was devoted to an exploration of comparative effectiveness research (CER). Jean-Frederic Colombel (New York, USA) described why CER is needed to help make informed clinical decisions. For this purpose, direct comparisons are required in the setting of day-to-day practice and in populations that are large enough to allow sub-group analysis. He highlighted the contrasts between clinical trials of efficacy and clinical practice and illustrated his presentation with examples of CER in IBD, including SONIC, REACT-1 and CALM. He concluded with a discussion of the challenges of CER and the priorities for future trials and recommended use of the GRACE checklist for anyone planning to set up or publish observational studies of comparative effectiveness.
Pieter Hindryckx (Gent, Belgium) reviewed the field of retrospective CER. The main problems with this type of research are the lack of control of exposure to the different treatments, the variability of the outcome assessments an d missing data.
Simon Travis (Oxford, UK) reviewed the literature on head-to-head trials. He discussed the important differences between superiority, equivalence and non-inferiority trials. To bring an excellent session to a close, the panel of speakers was joined by Elmer Schabel from the European Medicines Agency for a free-ranging discussion with good audience participation. All the panel were keen to see longer term trials of early disease to define whether disease modification could be achieved with acceptable long-term safety.