On 25 September 2014, the Committee for Medicinal Products for Human Use (“CHMP“) of the European Medicines Agency (“EMA“) adopted new guidelines on the evaluation of medicinal products for the treatment of irritable bowel syndrome (“IBS“) (the “New Guidelines“). The New Guidelines will come into effect on 1 April 2015.
The New Guidelines revise and expand on the previous “Points to Consider on the Evaluation of Medicinal Products for the treatment of Irritable Bowel Syndrome” (CPMP/EWP/785/97), which have been in operation since 2003. The New Guidelines are intended to assist applicants during the development of products for the treatment of IBS.
The New Guidelines introduce a number of changes from the previous “Points to Consider”, which are discussed below.
1. Rome III Criteria
Historically, there has been constant change in the classification criteria for IBS. The New Guidelines request that applicants use the now widely accepted Rome III criteria in the definition of their patient population to be included in clinical trials. Any alternative definition used during the conduct of clinical trials must be justified.
The Rome III criteria define the IBS population as follows:
- Recurrent abdominal pain or discomfort at least three days per month in the last three months (with symptoms being present for the last three months and onset at least six months prior to diagnosis) associated with two or more of the following:
- Improvement with defecation;
- Onset associated with a change in frequency of stool;
- Onset associated with a change in form (appearance of stool).
The sub-typing of IBS patients is performed by the predominant stool pattern present in a patient:
- IBS with constipation (IBS-C): hard or lumpy stools ≥25% and loose (or mushy) or watery stools in <25% of the bowel movements;
- IBS with diarrhoea (IBS-D): loss (mushy) or watery stools ≥25% and hard or lumpy stools <25% of the bowel movements;
- Mixed IBS (IBS-M): Hard or lumpy stools ≥25% and loose (mushy) or watery stools ≥25% of the bowel movements;
- Unsubtyped IBS: Insufficient abnormality of stool consistency to meet the criteria for IBS-C, D, or M.
2. Primary Endpoints
The New Guidelines continue to recommend the following two co-primary endpoints as the primary outcome:
- The patient’s global assessment of symptoms;
- The assessment of abdominal discomfort/pain.
The New Guidelines recommend the development and validation of patient reported outcome instruments for the use as primary outcome parameter, however such an instrument is not currently available. It is therefore recommended to assess the main symptomatology in at least partially validated scales/outcome parameters. The proposed primary endpoint should be an evaluation of abdominal pain and stool frequency.
3. Special Patient Groups
The New Guidelines include dedicated chapters on children, the elderly and gender. These chapters cover the conduct of clinical trials that incorporate these special patient groups. In particular, clinical trials should aim to include a population reflecting the epidemiology of the disease and include relevant proportions of elderly subjects and gender differences.
4. Geographic Region
The New Guidelines highlight that previously many development programmes for IBS treatments were aimed at the North American IBS population. However, it is considered advantageous to include European patients in global development programmes.