An international consensus group has for the first time defined a new set of core outcomes for research in adenomyosis. Their application in future studies hopes to encourage good clinical practice and ensure that outcomes of importance to patients are reported.
Painful periods, duration of menstrual bleeding and sexual function relating to quality of life are included in the first core outcome set (COS) developed for research in adenomyosis. A global group of health experts, women living with adenomyosis and patient organisations has agreed on 50 outcomes that should be reported in all studies investigating uterus-sparing interventions for treating the disease in premenopausal women.(1)
The authors of the COSAR study who identified these core outcomes write that they mark an ‘important step’ in standardising future research, will help in evidence gathering, stimulate good clinical practice and assist patients/clinicians in optimal decision-making. The COS, they report, is applicable to all uterus-sparing therapeutic interventions, including those guided by imaging techniques, and are grouped under nine categories: pain, uterine bleeding, reproductive outcomes, haematology, urinary system, life impact, delivery of care, adverse events, and reporting items.
A benign condition affecting the uterus, adenomyosis can be linked with a significant symptom burden of mainly painful or heavy periods – as well as reduced fertility and poor reproductive and obstetric outcomes.
Prevalence is high and the disease clinically relevant. Yet the COSAR authors highlight the paucity of well designed clinical trials comparing the options for treating adenomyosis, with studies using many different outcomes/outcome measures. Hence, the usefulness of available research for clinical practice and guidelines is very limited.(2)
The COSAR development process took place between March and December 2021. Stakeholders included healthcare professionals (eg, midwives, radiologists), researchers, patients/their partners with first-hand experience of adenomyosis, and patient advocate organisations including the World Endometriosis Society and the UK Endometriosis Foundation. For the purpose of the COS, adenomyosis was defined as the presence of ectopic endometrial cells and stroma within the myometrium.
A long list of 214 outcomes was identified using a systematic review (outcomes: 203), patient focus group workshops (outcomes: 5), and by a steering committee (outcomes: 6). Some outcomes were then merged leaving 71 which were evaluated by participants via a 2-step modified Delphi electronic survey (round 1: 501 people, 48 countries; round 2: 291 people, 38 countries (58% return rate)). Consensus for inclusion of an outcome was defined as 70% or more participants giving a high score (7-9) and fewer than 15% awarding a low score (1-3).
The steering committee, comprising nine adenomyosis specialists and one patient advocate, decided on the final COS of 50 core outcomes (24 specific and 26 generic) and also provided definitions. Of the 50, over a third (n=19) will only apply to certain study types, and 10 are reporting items.
Bloating as a pain outcome was among items not included (defined as 70% or more participants giving a low score (1-3) and fewer than 15% awarding a high score (1-3)). After discussion, it was decided this symptom was too non-specific and thus not a priority for inclusion. Health economic outcomes were excluded from the COS on the grounds they could be ‘methodologically challenging’ for many investigators but the steering committee said they should still be reported in research.
As for reproductive outcomes, a COS exists already on infertility so all items were included in the adenomyosis COS.(3) However, the steering committee decided to modify two definitions in the infertility COS: ‘viable’ was replaced with ‘live’ for early pregnancies; and eutopic pregnancies described as ‘normally sited (eutopic)’ rather than ‘intrauterine’ in line with ESHRE terminology.
The next step is to define measures for each of the outcomes listed and to monitor use of the COSAR with a view to appropriate modifications in future.
The authors say a high number of participants took part in the development process, that the views of patients were strongly represented, and that the COSAR process involved a ‘truly global’ representation of patients and healthcare professionals.
Limitations included under-representation of patients from low-income countries and of participants from continents outside Europe. In their findings, the authors emphasise the significant lack of scientific evidence regarding symptoms caused by adenomyosis and those which could be related to associated disorders (eg, endometriosis), and this may affect how patients report outcomes.
The implication of the study findings is that the quality of reporting will improve if researchers implement this COS. But it’s clear there is more work to be done. According to the authors, knowledge gaps persist because researchers still lack ‘important tools’, such as a disease-specific health-related quality of life (HR-QoL) questionnaire and the validation of generic HR-QoL instruments.
An ‘urgent need’ also exists for this COS and further research to identify additional relevant outcomes. More studies are needed, adds the report, which are designed to determine which symptoms are specific to adenomyosis and how they affect quality of life.
1. Tellum T, Naftalin J, Chapron C, et al. Development of a core outcome set and outcome definitions for studies on uterus-sparing treatments of adenomyosis (COSAR): an international multistakeholder-modified Delphi consensus study. Human Reprod July 2022; doi.org/10.1093/humrep/deac166/6652276
2. Tellum T, Omtvedt M, Naftalin J, et al. A systematic review of outcome reporting and outcome measures in studies investigating uterine-sparing treatment for adenomyosis. Hum Reprod Open 2021 (3); doi.org/10.1093/hropen/hoab030
3. Duffy JMN, Bhattacharya S, Bhattacharya S, et al. Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study. Fertil Steril 2020; 115: 201-212. doi.org/10.1016/j.fertnstert.2020.11.013