Prevention of Opioid-induced Constipation in Patients With Advanced Cancer

A clinician-administered patient-reported questionnaire to assess clinically significant constipation, validated in patients receiving opioids for chronic non-malignant pain and for malignant pain (Abramovitz 2013, Rentz 2009 and 2011). It consists of three questions, assessing ease of defecation, feeling of incomplete bowel evacuation and personal judgement of the patient regarding constipation, each during the last 7 days and each rated on a scale of 0 (best possible outcome) to 100 (worst possible outcome). A total score ≥30 (mean of the three separate scores) indicates clinically significant constipation. A change of the total score of >12 is regarded as clinically meaningful. It has been used in a large observational study in cancer patients receiving opioids (Davies 2021) and in randomised trials of opioid antagonists for OIC (Ahmedzai 2012, Dupoiron 2017, Leng 2020, Poelaert 2015). It has been recommended as the assessment tool of choice for OIC (Argoff 2015, Farmer 2019).

A self-administered, generic assessment tool developed by the EuroQol Group, a network of international research teams, and consists of questions on five dimensions of health (i.e., mobility, self-care, pain/discomfort, usual activities, and anxiety/depression) (Pickard 2007). It has been used in cost-effectiveness studies on OIC (Dunlop 2012, Hjalte 2016, Lawson 2016).

Rome IV criteria for opioid-induced constipation as judged by professional care givers (Davies 2021, Drossman 2016), including:

• straining during >25% of defecations
• lumpy or hard stools in >25% of defecations
• sensation of incomplete evacuation in >25% of defecations
• sensation of anorectal obstruction/blockage in >25% of defecations
• manual manoeuvres to facilitate >25% of defecations
• <3 spontaneous defecations per week At least two of these criteria have to be fulfilled in order to diagnose constipation, to be judged by the treating physician or clinical nurse specialists/nurse practitioners

Numeric Rating SDcale, ranging from 0 to 10

A single four-item question, ranging from unsatisfied to very satisfied.

All side-effects are scored on a four-point Likert scale (not at all, a bit, rather, very much):

• Bad taste
• Problems with swallowing
• Abdominal cramps
• Nausea
• Flatulence
• Diarrhea
• Other (to be specified by the patient)

We aim to perform a comparative cost-effectiveness of the laxatives. This requires data collection on healthcare procedures and QOL in responders, non-responders and patients with side-effects of laxatives for the follow-up period of the study. These healthcare procedures will be extracted from hospital databases and healthcare use outside the hospital will be collected with the iMCQ at 4 weeks. All individual health care procedures will be linked to their unit costs. Reimbursement prices issued by the Dutch Healthcare Authority and national reference prices will be used for this assessment as outlined in current Dutch pharmaco-economic guidance. The cost-effectiveness analysis will be performed using a decision tree including different branches for initial therapy and responders and non-responders. The costs and QOL of the patients in the trial will be used as input for this decision tree. Total costs and effects will be calculated by summing the costs and effects of each branch.