Given the prevalence of AUB, high-quality research on treatment modalities for this burdensome condition is imperative for the advancement of women’s health-related quality of life [17
]. In our systematic review, we identified 79 trials for AUB that reported 114 different outcomes, many of which attempted to evaluate outcomes from the patient perspective, a top priority in health research. However, the sheer number and variety of outcomes reported in the literature hinders comparing different interventions across different studies. This limits the utility of this literature for informing clinicians, patients, and policy makers about the respective benefits and harms of different interventions. In response to this dilemma, we generated an outcomes inventory and ranked the importance of outcomes in an explicit expert decision-making process to guide evidence synthesis and future research.
The outcome inventory generated included all clinically relevant patient-reported outcomes that have been used in past studies for AUB over the past 58 years. Categorizing the individual outcomes into overarching outcome domains and then rating each individual outcome in terms of “importance” for clinical decision making provides a point of reference for recommendations of outcomes to be used in future studies on AUB. Our ranking emphasizes patient-reported outcomes deemed to be important but not explicitly how to measure them, as currently, there is no definitive answer on how best to measure all of these outcomes. The variety of outcomes assessed and instruments used in our review highlights that there is no high-quality, standardized set of instruments that comprehensively evaluates outcomes for women with AUB that is universally accepted.
Although reliable, validated instruments exist for the specific determination of the amount of blood loss [20
]; there is no single instrument that is considered the standard for evaluating menstrual symptoms, AUB-related quality of life, sexual health, or satisfaction with treatment in women with AUB. Further research is needed in the development of AUB-related quality-of-life measures that are proven responsive to capture changes after treatment. Generic health-related quality-of-life questionnaires can be used to augment validated disease-specific measures of blood loss; however, some women with AUB may experience difficulty in answering generic questions about health perceptions because of the intermittent nature of AUB [14
]. As AUB symptoms can be chronic and intermittent, it is important to assess more than a single aspect of a woman’s bleeding experience, and that is why we have included all outcomes categories rated as “important” by our review group in the following recommendations.
Specification of important outcomes is a key step when developing a systematic review protocol to ensure that useful information is synthesized. The recently updated Cochrane Handbook for Systematic Reviews of Interventions recommends choosing a maximum of seven outcomes and to present the main findings on those in the “Summary of findings” table [25
]. This is because evidence synthesis across an excessive number of outcomes becomes confusing. The eight outcome categories proposed for AUB trials are not necessarily independent but capture different aspects of a disease that manifests with varying symptoms that can have variable impact on a woman’s health. Hopefully, going forward, single instruments will collapse the measurement of symptoms and manifestations across different categories, but at this point, the eight outcome categories are proposed as a first step to help with cleaning up a field plagued by a plethora of outcomes.
The problems encountered in this systematic review of AUB trials are not unique to gynecology. Similar strides for developing meaningful and parsimonious outcome measures have been undertaken in other medical disciplines. For example, OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials) has endeavored to improve national and international consensus on issues, such as minimum number of outcome measures to be included in treatment trials, and to decide on the magnitude of differences judged to be clinically relevant [26
4.1. Recommendations for outcomes in abnormal uterine bleeding trials
The following recommendations provide guidance for a more standardized assessment and reporting of outcomes specifically for trials for AUB. Our recommendations should be considered supplemental to the CONSORT guidelines [27
] and the extensions of the CONSORT guidelines for trials assessing nonpharmacological treatments [28
] and for assessing the harms [16
To fully assess the effects of an intervention, we recommend assessing outcomes in all eight outcome categories (). Assessments of bleeding, quality of life, pain related to heavy bleeding, sexual health, and bulk-related complaints (in patients with leiomyomas) should be conducted both before and after treatment, and the change for each patient should be used as an analytic metric. Patient satisfaction, need for additional treatment, and adverse events should also be reported.
Recommended outcome categories in trials for abnormal uterine bleeding
The goal of any treatment for AUB is to reduce or eliminate bleeding, improve other associated symptoms, and improve quality of life. We suggest that bleeding be assessed based on patient-reported amount, frequency of menses, duration of bleeding, and regularity of menses [29
]. Many studies include pain, an important symptom in terms of potential impact on patients’ health and well-being, as an outcome, and this should also be measured. Women with leiomyomata may also have symptoms specific to uterine size. Therefore, trials in women with leiomyomata should assess bulk-related symptoms as an outcome before and after treatment.
Condition-specific quality of life is a key patient-based outcome measure. The large personal burden of AUB lies in its adverse impact on quality of life [3
], and this is an important outcome for AUB research. Sexual health, another important part of a woman’s quality of life, may be adversely affected by AUB and may be affected differentially by different treatments for AUB. Thus, sexual health should also be assessed before and after treatment.
Many studies we reviewed included “satisfaction with treatment” as an outcome for AUB treatments. We rated satisfaction with treatment as an important outcome, given its face validity, despite the dependency of this outcome on a patient’s pretreatment expectations and goals. Measured as the sole outcome for a study, “satisfaction with treatment” is limited, as it provides no information in terms of which symptoms the treatment alleviated and why the patient is satisfied. Collected as one of several outcomes, satisfaction with treatment may still be helpful to inform patients in their selection of different therapies.
These recommendations are not meant to provide an exhaustive or definitive list of the exact data and outcome measures to be collected. There is no one standard measurement tool for the suggested outcomes included in these recommendations. In the absence of a standardized instrument for measuring outcomes in trials for AUB, researchers should consider combining available validated instruments for measuring outcomes or clearly explain how new instruments for measuring outcomes were developed specifically for their study. Researchers should clearly describe which instruments or methods were used to assess bleeding, related symptoms, quality of life, sexual health, and satisfaction. It would be ideal if investigators developed a validated measure or set of instruments that captured all AUB-related symptoms so that a standardized tool can be used in all future trials.
4.2. Strengths and limitations
One strength of this study is that the review group used a systematic process to identify RCTs for AUB and to list all outcomes reported in these trials. Additionally, a data-driven iterative expert consensus process was used to grade the importance of each of these outcomes. We used a voting process that left it to each group member to weigh the relative impact of the various considerations for what makes an outcome important for decision making and to arrive at a composite grade. Because this was, to some degree, subjective, we would have excluded individuals with any self-reported conflicts of interest, had there been any. As the GRADE working group states, knowledge about optimal strategies for making decisions about relative importance of outcomes remains limited. Regardless, it is desirable to make the process transparent and explicit [15
]. A limitation of the study is that there was no direct patient participation in deciding on the importance of outcomes for clinical decision making. For this reason, we referred to the available literature on patient experience with AUB and patient-based outcomes measures for AUB. For the same reason, we invited individuals with particular expertise in patient-reported outcome measures for AUB research to participate in the review group discussions.