Measuring health-related quality of life in the general population and Roma communities in Romania: study protocol for two cross-sectional studies

Introduction The importance of health-related quality of life (HRQoL) is increasing and many healthcare authorities recommend the use of measures that account for both mortality and morbidity. This study will determine, for the first time in Romania, value sets for EuroQoL-five-dimensions-3-level (EQ-5D-3L) and EQ-5D-5L questionnaires and their population norms (study 1). It will also compare the HRQoL (measured with EQ-5D-5L) of Roma communities in Romania with that of the general population (study 2). Methods and analysis Cross-sectional studies of face-to-face interviews conducted in representative samples of the Romanian general population and Romanian Roma communities. 1614 non-institutionalised adults older than 18 years will be interviewed using a computer-assisted interview for study 1. Participants will complete EQ-5D-3L and 5L, 13 composite time trade-off tasks (cTTO), 7 discrete choice experiment questions (DCE) and sociodemographic questions. For study 2, 606 non-institutionalised self-identified Roma people older than 18 years will be interviewed using a pencil-and-paper interview. Participants will complete EQ-5D-5L and the same sociodemographic questions as for study 1. The 3L value set will be estimated using econometric models and the cTTO data. cTTO and DCE data will be used for the 5L value set. Population norms will be reported by age and gender. The ORs for reporting different levels of problems and the most common health states in the population will be estimated. For study 2, t-tests and analysis of variance will be used to explore differences between groups in HRQoL and for each EQ-5D. Ethics and dissemination Ethics approval was given by the National Bioethics Committee of Medicines and Medical Devices Romania and Newcastle University’s Research Ethics Committee. Results will be published in peer-reviewed journals, presented at scientific conferences and on the project’s website. The EQ-5D-5L anonymised datasets will be deposited in a centralised repository. Two public workshops with local authorities, physicians and patients’ associations will be held.

Study One: Part 1: Developing Romanian Value Sets EQ-5D-3L & 5L 1. Data Quality Control : Utilizes online QC tool by EuroQol that automates production of QC reports but criteria of 'flagging' a poor performing interviewer is not defined. 2. Statistical Analysis : New methods of modelling EQ-5D-5L (Feng Y, Devlin NJ, Shah KK, Mulhern B, van Hout B. New methods for modelling EQ-5D-5L value sets: An application to English data. Health Economics. 2018;27:23-38.) Just adding this on for alternative methods to try maybe (?) since it wasn't in the list of references.
Study One: Part 2: Population Norms for Romanian General Population using EQ-5D-3L & 5L 1. Statistical analysis : Not described in depth. How will the population norm be determined? Using mean values? The study questionnaire of study 1 includes the EQ-5D-3L, whereas the questionnaire of study 2 includes the EQ-5D-5L and EQ-5D-3L questionnaire. Why do you include both versions of the questionnaire of study 1? Why not only include the EQ-5D-5L? We have now corrected and checked again our manuscript for spelling mistakes.

VERSION 1 -AUTHOR RESPONSE
Methods and analysis I. Aim and objectives Our specific objectives are: 1. To develop a value set for EQ-5D-3L and 5L based on societal preferences in Romania (Study one, an Omnibus survey) 2. To determine the population norms of the Romanian version of EQ-5D-3L and 5L (Study one, an Omnibus survey) Comment 1 The 5 blocks of questionnaires for Study One is pretty heavy on the interviewer & respondent. Wonder if it might cause interviewer/respondent fatigue and affect the outcome? Can the EQ-VT Software capture the quality accurately in this situation? Was it meant for 3L & 5L valuation simultaneously?
Authors' response: Thank you very much for your comment: the burden of the interview, and specifically of the time-trade off tasks (TTO), is indeed high for both the interviewer and respondent. For the 301 interviews we have conducted up to the 31st of March 2019 the average duration of an interview was of 49 minutes (SD=19 minutes) and the average duration of a TTO task was of 1.35 minutes (SD=1.1 minutes). In order to reduce the burden, face-to-face interviewing was chosen to administer the questionnaires in spite of the higher costs. This mode conveys more easily interviewers' engagement and enthusiasm to respondents, making them more motivated and less likely to shortcut the tasks (1). Additionally, the QC tool developed by the EuroQoL Foundation can be used to detect respondents' satisficing by observing and comparing the TTO value distribution by interviewer with the overall TTO value distribution. If satisficing is observed, interviewers are advised, by phone or email, to engage respondents more either by providing additional explanations in words easier to understand, or by encouraging respondents to think-aloud or by reminding them the importance of the study. In terms of interviewers' fatigue, our interviewers are hired part-time, so they generally perform less than five interviews per day. Additionally, interviews are performed in respondents' homes thus helping to reduce the potential boredom associated with repeating under the same circumstances the same scenario multiple times. The EQVT software was developed to allow the estimation of the EQ-5D-5L value set. However, the software does allow the addition of other methodological objectives. The version of the software we are currently using was initially developed for the US EQ-5D-5L valuation study (2). This valuation study included an additional sub-aim to directly compare EQ-5D-3L and 5L value sets developed using time trade-off (TTO) values. After the US valuation study, the same software was used in Hungary to develop both 3L and 5L value sets (study still ongoing). Given that Romania does not currently have a value set for either of the EQ-5D versions, we decided to use this software to simultaneously develop the 3L and 5L value sets for our country as it allows an improved quality control.
A. Study One: Part 1: Developing Romanian Value Sets EQ-5D-3L & 5L Comment A.1 -Data Quality Control: Utilizes online QC tool by EuroQol that automates production of QC reports but criteria of 'flagging' a poor performing interviewer is not defined.

Authors' response:
According to the quality control process developed by the EuroQoL foundation, an interview is flagged if either the worse than death element is not shown in the wheelchair example, or the duration of the explanations provided for the cTTO task in the wheelchair example is less than three minutes, or if the duration of the ten cTTO tasks for EQ-5D-5L is less than five minutes or if the value for the worse health state (55555) is not the lowest or at least 0.5 higher than the value assigned to the health state with the lowest value (3). We have now included a short description of the criteria for flagging a poor performing interviewer in the manuscript as well.
Methods and analysis V.
Data collection Study One B.
Data quality control Data quality control checks will be run after each interviewer will have performed a round of 10 interviews. Interviews are flagged as non-compliant if the explanations for the first two examples last for less than three minutes, if the worse than death (WTD) element is not shown in the examples, if the duration of cTTO tasks is less than five minutes, or if the value for the worse health state is not the lowest and at least 0.5 higher than that of the state with the lowest value 30 . Poor performing interviewers will be re-trained and removed from the team if no improvement is seen after re-training.
Comment A.2 -Statistical Analysis: New methods of modelling EQ-5D-5L (Feng Y, Devlin NJ, Shah KK, Mulhern B, van Hout B. New methods for modelling EQ-5D-5L value sets: An application to English data. Health Economics. 2018;27:23-38.) Just adding this on for alternative methods to try maybe (?) since it wasn't in the list of references.
Authors' response: Thank you for the comment: we have now updated the Analysis section of our manuscript.
Methods and analysis VI. Analysis Study one A hybrid model that uses both cTTO and DCE data will also be developed for the EQ-5D-5L value set using the most innovative modelling techniques 31 32 .

B. Study One: Part 2: Population Norms for Romanian General Population using EQ-5D-3L
& 5L Comment B.1 -Statistical analysis: Not described in depth. How will the population norm be determined? Using mean values?
Authors' response: EQ-5D-3L & 5L responses will be scored using the value sets developed. Summary statistics, such as mean, standard deviation, median, percentile 25 and 75 will be presented by age groups and sex. We will also present summary statistics (mean, standard deviation, median, percentile 25 and 75) for the EQ visual analogue scale (EQ-VAS). The Analysis section of our manuscript has now been updated to include this information.
Methods and analysis VI.
Analysis Study one Respondents' responses to both EQ-5D-3L and 5L descriptive systems will be scored using the respective value sets and summary statistics (mean, standard deviation, median, 25 th percentile and 75 th percentile) by age groups and sex will be presented (population norms for the value set/utility index). The same summary statistics stratified by age groups and sex will also be presented for the EQ-VAS (population norms for EQ-VAS). The distribution of people and the odds ratios for reporting different levels of problems or any problem in all dimensions of the two EQ-5D questionnaires will be calculated and stratified by sociodemographic variables. The frequency of the most common health states in the general population in Romania will also be determined.

C. Study Two: Population Norms for Roma Population
Comment C.1 -To check normality of HRQoL before using t-test/ANOVA. Most HRQoL data will not have a normal distribution.

Authors' response:
Thank you for the comment: we have now updated the Analysis section of Study two.
Methods and analysis VI.
Analysis Study two If the data follows a normal distribution, t-tests and ANOVA analysis will be used to reflect differences across groups in HRQoL and for each dimension of the EQ-5D-5L questionnaire, otherwise nonparametric tests will be used. This protocol describes the study aims, sampling strategy and study design of each of the sub studies very clearly.

Comment 1
In the introduction section the authors write: "Health-Related Quality of Life (HRQL) can be described as a patient's emotional view on the effect illness and its associated treatment(s) can have on his/her everyday life, physical, mental, social functioning and prosperity." Can we describe it as a patient's emotional view? Do you (measure it?) from patient's perspective? Emotional view and patient's perspective are not the same concepts.

Introduction
HRQoL is a multidimensional concept that includes physical, psychological, functional, and social aspects 1 regarding a person's perception of the impact of health status on quality of life 2 .