Clinical and cost-effectiveness of medical management versus surgery for deep infiltrating endometriosis: synopsis from the DIAMOND RCT

BACKGROUND: Deep endometriosis causes significant pain which adversely affects quality of life and utilises healthcare and wider societal resources. Laparoscopic excision of endometriosis has shown to improve pain symptoms in observational series but 1 in 14 patients experience serious surgical complications. Medical management centres around hormonal treatment, which is less risky and has been shown to be efficacious but can cause troublesome side effects and is incompatible with conception. There are no randomised controlled trials providing conclusive comparative evidence on clinical and cost-effectiveness of these treatments. OBJECTIVE(S): To compare the clinical and cost-effectiveness of laparoscopic surgery versus optimised medical treatment for managing deep endometriosis. DESIGN AND METHODS: A multicentre randomised controlled trial, with an internal pilot phase, and economic evaluation, to compare early planned laparoscopic surgery (first attempt at definitive surgery) with or without adjuvant medical treatment versus optimised medical management alone in women with deep endometriosis. SETTING AND PARTICIPANTS: Women presenting with pelvic pain associated with surgically or radiologically confirmed deep endometriosis, suitable for either surgical or medical management, recruited and managed at accredited British Society for Gynaecological Endoscopy Endometriosis Centres. INTERVENTIONS: Early planned laparoscopic surgery to excise deep endometriosis (with or without medical treatment) or medical management alone. MAIN OUTCOME MEASURES: The primary outcome was condition-specific quality of life measured using the pain domain of the Endometriosis Health Profile-30 at 18 months post randomisation. The primary health economic outcome was to be incremental cost per quality-adjusted life-year gained at 18 months. Secondary outcomes included quality of life (Endometriosis Health Profile-30), pain, complications, occupational and reproductive outcomes. RESULTS: Three hundred and seventy-seven patients were screened, 103 were eligible and 18 were randomised. Of the eight patients allocated surgery, only one had had their surgery by the time of trial closure and six participants (2/4, 50% allocated surgery and 4/8, 50% allocated medical treatment) had reached the first trial end point at 3 months. No participant reached the primary outcome at 18 months post randomisation. LIMITATIONS: The overriding limitation was failure to recruit participants at a satisfactory rate resulting in a final sample of only 18 patients with a target of 320 (inflated to 400 to account for a projected 20% attrition rate). Given the nature of the intervention, it was not possible to blind either the care providers, investigators or participants to their allocated group. CONCLUSIONS: The clinical question regarding the effectiveness of surgical removal or optimised medical treatment for deep endometriosis remains relevant. It remains unanswered because of the early closure of the trial due to failure to recruit participants. To deliver important surgical studies in this area will require potentially different study designs with new and innovative strategies to educate, enthuse and incentivise both patients and clinicians. There is a need for simplified processes to expedite study site set up, along with increased accountability and funding to motivate local research and development departments and principal investigators. FUTURE WORK: The DIAMOND trial has shed light on some of the obstacles preventing the successful delivery of robust trials in deep endometriosis thereby informing future study designs. FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR130310.