Study YearRandom assignment?Allocation concealed?Groups similar at baseline?Eligibility criteria specified?Blinding: outcome assessors, care provider, patient?Intention-to-treat analysis?Maintenance of comparable groups?Reporting of attrition, contamination, etc?Differential loss to followup or overall high loss to followup?Quality ScoreFunding sourceExternal validity
Al-Azzawi, 2003
Buckler, 2003
YesYesMore oophorectomy in vaginal ring group (25% vs 21%)YesYesYesYesAttrition yes34/159 (21%) withdrew (by 12 weeks): 20.2% vaginal ring oral E2 vs 22.7%GoodSponsored by Galen Holdings PLC.Fair
Gelfand 2003YesNot reportedMore smokers in Prefest group (10.2% vs 1.7%); Months since LMP 30.6 prefest vs 34.2 placeboYesYesNot clear- number randomized not reportedNot clearAttrition yes3% of prefest and 5% of placebo withdrewFairSupported by Janssen- OrthoFair
Yang, 2002Method not reportedNot reportedYesYesStates double blind, but no detailsNoNot clearOnly total withdrawals reported, not reported by group28.6% withdrew, numbers in each group not givenPoorNot reported.Fair
Speroff, 2003YesNot reportedYesYesYes"Modified ITT analysis": 8/333 women did not provide postbaseline data, not included, but other withdrawals included in ITT analysis.Not clearAttrition yes16% withdrew: 12.4% in E2 vaginal ring 50 mcg, 9.8% in E2 vaginal ring 100 mcg, and 26.9% in placebo group withdrew (p=0.007 and p=0.001 vs placebo)FairSupported by Waner Chilcott, a division of Galen Holdings. Authors have received speaking and consulting honoraria from the company. Author owns stock in the company.Fair
Saure, 2000Yes; methods NRNRYesYesDouble-blindNRUnclearSome15% E2; 16% E2VFairNRFair
Good, 1999Yes; methods NRNRYesYesDouble-blindNRUnclearSome15% overallFairThera Tech Inc.Fair
Gordon, 1995Yes; methods NRNRYesYesDouble-blindUnclearUnclearSome13–26% Rx; 30% placeboFair3MFair
Studd, 1995Yes; methods NRNRYesYesDouble-blindYesUnclearSome16% overallFairNRFair
Freedman, 2002Yes; methods NRNRYesYesDouble-blindNRUnclearNRNRFairNIHFair
Jirapinyo et al, 2003Yes; methods NRMethod NRMean Greene score slightly higher in E2 than placebo (20.1; SD 10.1 vs 17.9; SD 13.3)YesDouble-blind; methods NRNo; PP analysis excludes 30% randomizedUnclearAttrition yes16.7% withdrew in E2; 11.7% in placeboFairNovo Nordisk Asia Pacific Pte Ltd.Fair
HRT-naïve women only
Notelovitz, 2000aYesYesSlight variationYesDouble-blindYesUnclearSomeRx groups 11–21%; placebo 17%FairNovo NordiskFair
Notelovitz, 2000bYes; methods NRNRSlight variationYesDouble-blindNRUnclearSome16% overallFairNRFair
Utian, 2001YesYesYesYesDouble-blindYesUnclearSome19% overall; 23% placebo; 30% 0.625 mg/day; 14–19% in other groupsFairWyeth-AyerstFair
Utian et al., 2004YesYesSlight, non-significant racial variation among Rx groupsYesDouble-blindNo (excludes 5 withdrawn after 1-day washout period)UnclearAttrition yes; Adherence yesDiscontinuations:
Placebo: 24%
0.3 mg: 19%
0.625 mg: 15%
1.25 mg: 17%
Discontinuation not sig. different between groups (P>0.05).
FairEndeavor Pharmaceuticals, Inc.Fair
Bacchi-Modena, 1997Yes; methods NRNRYesYesDouble-blindYesUnclearSome6% Rx; 15% placeboFairNRFair
De Aloysio, 2000Yes; methods NRNRSlight variationYesDouble-blindYesUnclearSome7% Rx; 25% placeboFairNRFair
de Vrijer, 1999Yes; methods NRNRYesYesDouble-blindYesUnclearSome11% overallFairNRFair
Notelovitz, 2000cYes; methods NRNRYesYesDouble-blindYesUnclearSome5% overall (11 Rx, 1 placebo)FairRhone-Poulenc RorerFair
Shulman, 2002YesYesYes except for smokingYesYesYesUnclearSome3% overallFairBerlex LabsFair
Speroff, 1996Yes; methods NRYesDescribed, data NRYesYesUnclearUnclearSome<20% Rx; 31% placeboFairPark DavisFair
van Holst, 2000Yes; methods NRNRDescribed, data NRYesDouble-blindYesUnclearSome7% overallFairNRFair
van Holst, 2002Yes; methods NRNRSlight variationYesDouble-blindYesUnclearSome17% overallFairNRFair
Utian, 1999Yes; methods NRYesSlight variationYesDouble-blindYes, data NRUnclearSome10% overall (12 RX; 8 placebo)FairLab Fournier SAFair
Wiklund, 1993Yes; methods NRNRYesYesUnclear if double-blindYesYes, data NRSome4% Rx; 8% placeboFairNRFair

From: Appendix E. Quality scores of reviewed hot flash/flush trials

Cover of Drug Class Review: Hormone Therapy for Postmenopausal Women or Women in the Menopausal Transition Stage
Drug Class Review: Hormone Therapy for Postmenopausal Women or Women in the Menopausal Transition Stage: Final Report Update # 3 [Internet].
Nelson HD, Nygren P, Freeman M, et al.
Portland, (OR): Oregon Health & Science University; 2007 Oct.
Copyright © 2007, Oregon Health & Science University, Portland, Oregon.

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