Quantitative analysis of placebo response and factors associated with menopausal hot flashes

Li, Lujin; Xu, Ling; Wu, Jiang; Dong, Lidan; Lv, Yinghua; Zheng, Qingshan

doi:10.1097/gme.0000000000000858

Cited by 21 publications

(30 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some clinical evidence was consistent with these results [16,32]. erefore, we think that there is a high placebo response rate during hot flash treatment [44,45]. SSRIs/SNRIs ranked lower than all other treatments except no treatment/waitlist.…”

Section: Summary Of Evidencesupporting

confidence: 71%

Nonhormonal Hot Flash Management for Breast Cancer Survivors: A Systematic Review and Network Meta‐Analysis

Liu

Nie

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Aim of the Study. Hot flashes impair the quality of life of breast cancer survivors. Nonhormonal management is an important consideration. The objective of this network meta-analysis (NMA) is to compare the therapeutic efficacy and safety of nonhormonal hot flash treatments for breast cancer survivors. Materials and Methods. We conducted a systematic literature search in PubMed, Cochrane Central Register of Controlled Trials, Embase, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), Wan Fang, and VIP up to May 2018. Randomized controlled trials (RCTs) reporting nonhormonal hot flash treatments for breast cancer survivors were included. Primary outcome measurements were hot flash frequency and hot flash score of posttreatment. The methodological quality of each study was assessed with Cochrane’s risk of bias tool. Results. 16 RCTs involving 2,349 participants were included. The nonhormonal therapies used in the included studies were classified as follows: lifestyle changes, mind-body techniques, dietary/supplements, SSRIs/SNRIs, other medications, and other therapies. Pairwise meta-analysis showed that the general effect of nonhormonal management was statistically more effective than no treatment/placebo/sham in reducing hot flash frequency (SMD = −0.60, 95% CI [−1.13, −0.06]; P=0.03)) and hot flash score (SMD = −0.38, 95% CI [−0.68, −0.08]). For hot flash frequency, results from the NMA showed that there was no statistically significant difference between any two of the nonhormonal treatments. Another NMA result indicated that acupuncture (other therapies) was 16.05 points more effective in reducing hot flash scores than no treatment/waitlist (SMD = −16.05, 95% CI [−30.2, −1.99]). These results were statistically significant. Acupuncture was also ranked the optimal nonhormonal therapy for both hot flash frequency and hot flash score. The safety analysis showed that there were few related adverse events during acupuncture and that drug related adverse reactions could have also occurred in studies using drug interventions Conclusions. This network meta-analysis comparing nonhormonal treatments suggested that acupuncture might be more effective in improving hot flashes for breast cancer survivors. A pronounced placebo response was found during hot flash treatments. The evidence of safety for nonhormonal therapies was also insufficient. Therefore, at present, we cannot make confirmative recommendations of nonhormonal hot flash management for breast cancer survivors. This study is registered with PROSPERO (CRD42018082008).

show abstract

Section: Summary Of Evidencesupporting

confidence: 71%

Nonhormonal Hot Flash Management for Breast Cancer Survivors: A Systematic Review and Network Meta‐Analysis

Liu

Nie

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…No clear explanation can be given for the observed large placebo effect in the present study, although this has also been described by others in trials using classic estrogens. 25 The relatively high E2 levels at baseline and also at week 12 (Table 5 ) in the placebo group (mean ± SD 11.4 ± 16.5 pg/mL with min-max values of <5 and 86 at baseline, and 11.6 ± 27.8 pg/mL with min-max values of <5 and 180 at Week 12, respectively), were higher than the E2 levels recorded in the 15 mg E4 group (6.1 ± 2.4 pg/mL, min-max values of <5-15 at baseline, and 5.7 ± 2.2 pg/mL, min-max values of <5-19 pg/mL at week 12). This large difference in E2 levels observed between the placebo and the 15 mg E4 groups may have played a role (as observed in the post hoc analysis using E2 levels as a covariate), and suggests that some women may have been perimenopausal with some fluctuating, unpredictable increases in residual ovarian activity.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, considerable variability in the placebo response may occur and is influenced by numerous nonspecific factors. These include a higher response rate in trials of hormonal versus nonhormonal drugs, 25 , 27 severity of symptoms, anxiety, mood changes, treatment expectation both by clinician and patient, suggestibility, ethnicity, current smoking, or BMI more than 30. All these factors may contribute to a greater placebo response with a decrease in HF frequency more than 30% versus baseline, not only transiently, but also for a sustained period of time.…”

Section: Discussionmentioning

confidence: 99%

A multicenter, randomized study to select the minimum effective dose of estetrol (E4) in postmenopausal women (E4Relief): part 1. Vasomotor symptoms and overall safety

et al. 2020

View full text Add to dashboard Cite

Objective: The aim of this study was to select the minimum effective dose of estetrol (E4) for the treatment of vasomotor symptoms in postmenopausal women. Methods: This was a multicenter, randomized, double-blind, placebo-controlled study. Postmenopausal women ( n = 257, of whom 32 were hysterectomized) aged 40 to 65 years, with ≥7 moderate to severe hot flushes (HFs) per day, or 50 or more moderate to severe HFs weekly, received 2.5, 5, 10, or 15 mg E4, or placebo once-daily for a period of 12 weeks. Efficacy was assessed by recording the frequency and severity of HFs. Overall safety was assessed by recording adverse events, measuring endometrial thickness, and monitoring bleeding patterns. Treatment groups were compared using analysis of covariance. Results: The frequency of moderate to severe HFs decreased with all E4 doses. The difference in the percentage change of weekly HF frequency was significant for 15 mg E4 versus placebo at both W4 (−66% vs −49%, P = 0.032) and W12 (−82% vs −65%, P = 0.022). The decrease in severity of HFs was significantly more pronounced for 15 mg E4 than for placebo at both W4 (−0.59 vs −0.33, P = 0.049) and W12 (−1.04 vs −0.66, P = 0.049); the other doses failed to achieve statistical significance. In nonhysterectomized women, endometrial thickness increased during treatment and normalized following progestin treatment at study completion. No endometrial hyperplasia was observed. Conclusions: Estetrol 15 mg is considered to be the minimum effective daily oral dose for treatment of vasomotor symptoms. Its current seemingly favorable safety profile is further to be confirmed in phase 3 clinical development. Video Summary: .

show abstract

“…Illustrative Applications: References 33,35,37,39,40 What is the shortest duration of a proof-ofconcept study to provide informative data to drive reliable phase III decisions and designs?…”

Section: Illustrative Applications: Reference 21mentioning

confidence: 99%

“…Longitudinal MBMA models describing the time course of efficacy of drugs within or across therapeutic classes within the context of a disease progression modeling framework have been developed across several therapeutic areas. Examples include rheumatoid arthritis, psoriasis, osteoporosis, menopausal hot flashes, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, obesity, diabetes, and Alzheimer's disease . These typically invoke a common structural model of time course of efficacy with the drug effect described as an additional term over the placebo effect and the time course of disease progress.…”

Section: Mbma For Optimizing Designs and Decisions In Drug Developmentmentioning

confidence: 99%

Model‐Based Meta‐Analysis: Optimizing Research, Development, and Utilization of Therapeutics Using the Totality of Evidence

Upreti

Venkatakrishnan

2019

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Model‐based meta‐analysis (MBMA) is a valuable component of the quantitative pharmacology toolkit for model‐informed drug discovery and development. It enables principled decision making with a totality of evidence mindset through integration of internal and external data across multiple dimensions (e.g., targets/mechanisms, molecules/drugs, doses/regimens, diseases/indications, populations, endpoints, and clinical trial designs). MBMA distinguishes itself from traditional meta‐analysis by infusing pharmacologic plausibility into the statistical rigor that typifies meta‐analytic data integration. This is possible through mechanism‐informed formulation of pharmacologically inspired cause–effect and dose‐response relationships, time course of treatment effects, and interrelationships between proximal and distal outcomes of modulation of disease biology and pathophysiology. In this review, we offer a question‐based approach to enhance appreciation of the value of MBMA across the continuum from drug discovery and translational research through clinical development, comparative effectiveness research, and postapproval optimization of therapeutics using illustrative examples across therapeutic areas.

show abstract

Quantitative analysis of placebo response and factors associated with menopausal hot flashes

Cited by 21 publications

References 26 publications

Nonhormonal Hot Flash Management for Breast Cancer Survivors: A Systematic Review and Network Meta‐Analysis

Nonhormonal Hot Flash Management for Breast Cancer Survivors: A Systematic Review and Network Meta‐Analysis

A multicenter, randomized study to select the minimum effective dose of estetrol (E4) in postmenopausal women (E4Relief): part 1. Vasomotor symptoms and overall safety

Model‐Based Meta‐Analysis: Optimizing Research, Development, and Utilization of Therapeutics Using the Totality of Evidence

Contact Info

Product

Resources

About