Variation in outcome reporting and measurement tools among treatment trials for GSM

August 28, 2020

Considerable heterogeneity exists in reported outcomes and measures used in clinical trials of treatments for genitourinary syndrome of menopause (GSM), which impacts between 40% and 60% of postmenopausal women, according to a systematic review in the journal Menopause.

However, there is uncertainty over which outcomes best represent patient priorities and symptoms.

The authors searched PubMed, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) through December 2018 for randomized controlled trials in English language with a primary or secondary outcome of genitourinary symptoms associated with menopause.

The 109 studies that met inclusion criteria were from 1979 to 2018, with data from 30,792 women and 34 countries.

Overall, 48 different outcomes were reported, with "atrophy" as the most prevalent (51% of studies), followed by measures of sexual function (17%).

Other measured outcomes included dyspareunia, vaginal dryness during intercourse and vaginal lubrication.

In total, the studies used 21 patient-reported and 22 clinician-reported measurement tools for genitourinary symptoms. All but one study included patient-reported symptoms, “suggesting that the patient experience is considered an essential component of treatment efficacy,” wrote the authors.

However, patient-reported symptoms consisted of 21 different measures and 39 symptom combinations, which “prevents aggregation and direct comparisons between treatments, limiting understanding about which treatments are most beneficial for patients,” wrote the authors.

Clinician-reported scales of vulvovaginal appearance were used in 33% of trials, with extensive variation in what was measured and reported.

Cytological measures from the vaginal epithelium were the most commonly used objective tools, reported in 70% of the studies. In fact, vaginal epithelial cytology is required for FDA approval of new treatments for GSM.

One of the challenges of the studies was use of varied terminology to describe similar symptoms, such as ‘‘vaginal atrophy’’ and ‘‘vulvovaginal atrophy’’ or ‘‘urogenital atrophy’’ and ‘‘urogenital aging.” But there was no consistency in defining these terms.

While most studies defined atrophy as vaginal dryness, itching, and dyspareunia, other studies included symptoms of both vaginal and vulvar itching/irritation/soreness. Some studies also included urinary symptoms and pain or bleeding associated with intercourse to define atrophy.

“Our findings are consistent with previous systematic reviews comparing the efficacy of interventions for genitourinary symptoms in postmenopausal women, which concluded that meaningful comparisons between treatments for genitourinary symptoms were limited by inconsistency in outcome measures,” wrote the authors.

Introduction of the term GSM by the North American Menopause Society (NAMS) in 2014 has improved consistency in reporting; however, specific tools to measure the condition are still in development.

The FDA recommends three primary endpoints for clinical trials of treatment for GSM: mean change from baseline to week 12 of the most bothersome symptom and the clinician-obtained measures of vaginal pH and vaginal maturation index. But whether these measures reflect clinical outcomes or patient priorities is unclear, according to the authors.

Review findings have been shared with an international survey of stakeholders to determine priorities for outcome selection and reporting. The survey will then inform the development of a Core Outcome Set for use in future clinical trials by the COMMA (Core OutcoMes in MenopAuse) consortium.

Source:

Christmas MM, Song B, Bell RJ, et al. Variation in outcome reporting and measurement tools in clinical trials of treatments for genitourinary symptoms in peri- and postmenopausal women: a systematic review. Menopause. Published online July 13, 2020. doi:10.1097/GME.0000000000001570

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