MENQOL – The Menopause-specific Quality of Life Questionnaire

MENQOL – The Menopause-specific Quality of Life Questionnaire, by Catherine Acquadro, MD, Mapi Research Trust
We are pleased to share with you a summary of the MENQOL webinar held on April 21st, 2016. This webinar was led by Jacqueline E. Lewis, MD, CCFP, MSc, FCFP, Associate Professor Emerita of the Department of Family Medicine at the University of Calgary, and  Ben Rogers, Director of Technology Transfer and Scouting at MaRS Innovation, Toronto.
The webinar was divided into two parts: the first, presented by Dr. Lewis, covered all the development steps of the MENQOL and its derivatives; the second part by Ben Rogers was focused on copyright issues.
Please note that for referencing purposes the Maturitas publications are the official citations [1, 2].
 
MENQOL Development – Dr. Lewis
INTRODUCTION
At first, Dr. Lewis acknowledged the team involved in the development of the MENQOL and its three derivatives [1, 2], and addressed her sincere thanks to the many women who participated in this work. She recalled that the MENQOL went through two developmental phases, i.e., 1) Initial questionnaire development (1990-1996) [1]; and 2) Psychometric refinements and development of derivatives (1999-2003) [2].
When the development began, the concept of quality of life (QOL) was becoming increasingly important as an outcome measure in intervention trials. At that time, there was a definition that resonated with the team, i.e., condition-specific QOL defined as “the extent that the physical, emotional, social aspects of an individual’s life are intact and not adversely affected by that condition or treatment” [3]. Menopause was not considered as a disease, per se, but a normal transition to a different life state. Hence, the MENQOL in considered a condition-specific patient-reported outcome (PRO) measure, as opposed to a disease-specific questionnaire.
The goal was to develop a valid, reliable, responsive QOL questionnaire, specific to the early postmenopausal years, based on women’s reported experience
The women who participated in the development were the experts.
STEP 1: CONTENT IDENTIFICATION METHODS
An in-depth literature search on menopause and QOL was performed. All existing English language menopause questionnaires available at this time were retrieved and reviewed. A preliminary list of items was built. Then, eight in-depth qualitative interviews with women 2-7 years post-menopause were performed to add any possible missing concepts and items. Ten specialists, i.e., eight clinicians and two QOL researchers, reviewed the list of items for completeness. Write-in options were built into the reduction questionnaire pre-test. One item added this way contributed to the final questionnaire. This work resulted in 106 items and the following dimensions: Emotional, Intellectual, Social, Sexual, Physical, Sleep, Spiritual and Work Life.
STEP 2: DIMENSIONS TO DOMAINS
A priori decisions regarding domains were made: 1) To combine emotional, intellectual, social and spiritual dimensions into the Psychosocial Domain; 2) To combine sleep items into the Physical Domain; 3) To remove vasomotor items from the Physical Dimension and to create a Vasomotor Domain; 4) To create a Sexual Domain (the first for a menopause QOL questionnaire); and 5) To develop a Work life Domain that the literature considered an important dimension at this time. Two clinicians and one social scientist independently assigned all items to domains until consensus was reached.
STEP 3: ITEM REDUCTION STUDY
The item-reduction development phase recruited 88 women who were 2-7 years in post menopause (by classic definition of menopause, i.e., 12 months after last menses). Only women with a uterus were included who were not on hormone-replacement therapy for the last 6 months.
The reduction procedure was based on an impact scores reduction method, not a factor analysis, that had been used by Gordon Guyatt and colleagues at McMaster University. This method required a specific item format.

See Figure 1.

Figure 1. Item format for reduction phase

Each participant was asked to check the box whether she has experienced the item in the past month or past week, or not (frequency score). If yes, she was asked to rate how bothered she has been by the experience (bothered score).
Before analyzing the results of the reduction phase, a priori decisions were made that the final questionnaire would include around 30 items, and no domain should be fewer than 3 items.
The impact score was calculated as follows: IMPACT SCORE = % yes X mean bothered score / each item / all women.
Items with Impact scores 1.5 were removed from further consideration. This excluded all items in the Work Life Domain. The top 3 ranking items by domain were left in the domain. Then, all remaining items were removed from their domains and re-ranked high to low according to their impact score. They were then assigned sequentially to their predetermined domains until the resulting questionnaire had 29 items distributed in four domains: Physical Domain (16 items), Vasomotor Domain (3 items), Psychosocial Domain (7 items), and Sexual Domain (3 items).
The Analysis Score for psychometric property and trial outcome data analysis is different from the impact score used for questionnaire development.

See Figure 2.
Figure 2. Item Conversion for Analysis

STEP 4: PSYCHOMETRIC PROPERTY ASSESSMENT
For financial and expediency reasons, the psychometric studies were performed within a RCT of a hormone treatment for the menopausal condition. Participants in the RCT visited twice, 1 month apart, prior to randomization, to provide the MENQOL data for reliability, internal consistency, and responsiveness purposes [4].
Validity
Three types of validity were explored: face, content and construct validity.
A separate sample of 20 women was used to determine face validity: the score was 4.7 out of a possible 5. The panel of 10 experts was used to confirm content validity.
Construct validation involved comparison by domain with the Neugarten and Kraines’ Somatic, Psychosomatic and Psychologic subscales, the reported intensity of hot flushes, the General Well-Being Schedule, Channon and Ballinger’s Vaginal Symptoms Score and Libido Index, and the Life Satisfaction Index.
Discriminative construct validity (pre-randomization baseline) showed significant  correlation coefficients (all p0.001) of 0.69 for the Physical Domain, 0.66 and 0.40 for the Vasomotor Domain, 0.65 and -0.70 for the Psychosocial Domain, 0.48 and 0.38 for the Sexual Domain, and 0.57 for the quality of life question. See Table 1. Evaluative construct validity showed correlation coefficients of 0.60 (p0.001) for the Physical Domain, 0.28 (p=0.57) for the Vasomotor Domain, 0.55 (p0.001) and – 0.54 (p0.001) for the Psychosocial Domain, 0.54 (p=0.004) and 0.32 (p=0.124) for the Sexual Domain, and 0.12 (p=0.391) for the quality of life question.

Table 1. Construct Validity

Reliability
Test-retest reliability measures, using intra-class correlation coefficients, were 0.81, 0.79, 0.70 and 0.55 for the physical, psychosocial, sexual domains and the quality of life question. The intra-class correlation coefficient for the vasomotor domain was weak, at 0.37, and no explanation could be found.
For internal consistency, Cronbach’s alpha were all acceptable: 0.87 for the Physical Domain, 0.82 for Vasomotor, 0.81 for Psychosocial, and 0.89 for the Sexual Domain.
Responsiveness
Responsiveness measures how small a difference could be detected given the instrument’s variability in a stable situation- based on reproducibility analysis pre-randomization. A Minimum Clinicall Important Difference (MCID) of 1 was chosen for the MENQOL.
Responsiveness scores ranged from 0.78 to 1.33.

See more details in Table 2.

Table 2. Responsiveness of the MENQOL

STEP 5: DEVELOPMENT ISSUES
Following the psychometric study results, the team decided to address several issues:

The weakness of the reproducibility of the Vasomotor Domain (0.37) and Sexual Domain (0.7), over a 28 day interval.
The use of a one-week recall period: since some researchers wanted to use a one-week recall period, the team wondered about the impact on reproducibility. Would the reproducibility properties be altered by a shorter recall period?
The reflection of treatment side effects: How could the questionnaire reflect treatment side effects, such as vaginal bleeding with cyclical HRT or leg cramps with SERMS) which could negatively affect QOL? This led to the idea of developing a modified version, the MENQOL-Intervention (MENQOL-I) questionnaire, for use where certain treatment side effects could negatively impact the quality of life. The MENQOL-Intervention modifications involved the addition of three items to the physical domain.
Difficulties in completing the Sexual Domain: Participants in the RCT expressed difficulty to the research assistant with regard to answering “Vaginal dryness, during intercourse” if no partner or if the partner was impotent, while experiencing dryness anyway.
Missing data management.
Summary score computation.

All these issues were addressed by embedding the MENQOL and the MENQOL-I in randomized clinical trials [5, 6]. See more details in Tables 3 to 5. The addition of 3 items to the Physical Domain did not change the Cronbach’s alpha (Table 4). The ICC coefficients were improved for the Vasomotor Domain and the Sexual Domains of the MENQOL-I (Table 5).

Table 3. Description of trials: Hilditch [4], Lewis [5], Gelfand [6]

Table 4. Cronbach’s alpha measured for each trial

Table 5. Test-retest reliability for each trial

STEP 6: TRANSLATIONS
The following languages have documented linguistic and cultural validation: English  for Canada, USA, UK, Australia, and New Zealand; Spanish for Spain, Mexico, Argentina, USA, and Puerto Rico; French for Canada, France, and Belgium; Portuguese  for Brazil; Italian for Italy; German for Germany; Swedish for Sweden; Serbian for Serbia; Dutch for Netherlands, and Belgium.
In Norwegian, Polish, Finnish, and Danish, updating work is needed.
Literature suggests that there are versions in many Asian and South Asian languages, Farsi, Arabic, Russian, Ukrainian, Czech, Greek, Turkish, Yoruba, Hebrew, and in, Spanish for Colombia, Ecuador & Chile.
All require formatting to match the official 2005 MENQOL or MENQOL-I. Some require MENQOL to/from MENQOL-I conversion. Some must update a 1996-based version or change the recall period. Some require formal validation work.
Although some languages above are culturally and linguistically certified, others will require forma validation work.

CONCLUSIONS
There are four official MENQOL questionnaires (which include 3 derivatives works). Questionnaires differ only in the RECALL PERIOD and 3 items in the PHYSICAL DOMAIN
The best publication reference practice should cite 2 publications (i.e., [1, 2]). Researchers should ensure that they use the most helpful, appropriate questionnaire in their research. Good domain consistency and reliability data exists for women aged 41-62 years who were 1-9 years post last menses. Questionnaire items reflect the priority negative perceptions identified by women about their early postmenopausal experiences. Construct Validation by domain, although significantly correlated with the MENQOL domain scores, used instruments available in the early 90’s that frequently had less rigorous development than the MENQOL.
 
Copyright Issues – Ben Rogers
The MENQOL is subject to copyright: Copyright © 2005 Sunnybrook Health Sciences Centre. All rights reserved.
Sunnybrook Health Sciences Centre is one of the largest hospitals in Canada, and a research and teaching hospital affiliated with the University of Toronto.
The Primary Care Research Unit (development of the MENQOL) was established in 1985, is affiliated with the Department of Family & Community Medicine at University of Toronto. Research areas cover wait times, cognitive function, intervention evaluation, and family medicine practices.
Sunnybrook’s current Technology Transfer and Licensing Office and the services provided by the commercialization agency known as MaRS Innovation were established in November 2010. Sunnybrook’s intellectual property policy requires that ownership of all intellectual property developed by hospital staff be assigned to the hospital. Sunnybrook’s technology transfer office was not aware of the MENQOL until September 2011. Confirmatory assignment of the MENQOL was made to Sunnybrook in December 2011. In May 2014, Sunnybrook’s right to license MENQOL for commercial purposes was confirmed by the journal Maturitas, where the MENQOL and the MENQOL-I were first published.
In July 2015, a distribution agreement was signed with Mapi Research Trust for the MENQOL and the MENQOL-I. Three categories for licensing were established: 1) for academic researchers with no commercial funding, there is no license fees; 2) for academic researchers with commercial funding, a nominal license fee is requested; and 3) for CROs or pharmaceutical sponsors, a substantial fee is requested.
The MENQOL and MENQOL-I are available on PROQOLID via the ePROVIDE platform.
References
1. Hilditch JR, Lewis JE, Peter A, vanMaris B, Ross A, Franssen E, Guyatt GH, Norton PG, Dunn E. A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas 1996;24:161-175.
2. Hilditch JR, Lewis JE, Wong CJ. Further psychometric property development of the Menopause-Specific Quality of Life questionnaire and development of a modified version, MENQOL-Intervention questionnaire. Maturitas 2005;50:209-221.
3. Fletcher AE, Hunt BM, Bulpitt CJ. Evaluation of quality of life in clinical trials of cardiovascular disease. J Chronic Dis. 1987;40(6):557-69.
4. Hilditch JR, Lewis J, Ross AH, Peter A, van Maris B, Franssen E, Charles J, Norton P, Dunn EV. A comparison of the effects of oral conjugated equine estrogen and transdermal estradiol-17 beta combined with an oral progestin on quality of life in postmenopausal women. Maturitas. 1996 Jul;24(3):177-84.
5. Lewis JE, Nickell LA, Thompson LU, Szalai JP, Kiss A, Hilditch JR. A randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopause. Menopause. 2006 Jul-Aug;13(4):631-42.
6. Gelfand MM, Moreau M, Ayotte NJ, Hilditch JR, Wong BA, Lau CY. Clinical assessment and quality of life of postmenopausal women treated with a new intermittent progestogen combination hormone replacement therapy: a placebo-controlled study. Menopause. 2003 Jan-Feb;10(1):29-36