Journal of Clinical Epidemiology 59 (2006) 1049–1056 VEINES-QOL/Sym questionnaire was a reliable and valid diseasespecific quality of life measure for deep venous thrombosis Susan R. Kahna,b,*, Donna L. Lampingc, Thierry Ducrueta, Louise Arsenaulta, Marie Jose Mirond, Andre Roussind, Sylvie Desmaraise, France Joyald, Jeannine Kassisd, Susan Solymossb, Louis Desjardinsf, Mira Johria,d, Ian Shriera,b; for the VETO Study investigators a Centre for Clinical Epidemiology and Community Studies, Jewish General Hospital, Montreal, Quebec, Canada b McGill University, Montreal, Canada c Health Services Research Unit, London School Hygiene & Tropical Medicine, London, United Kingdom d Universit e de Montr eal, Montr eal, Quebec, Canada e Centre Hospitalier Pierre Boucher, Longueuil, Quebec, Canada f Universit e Laval, Qu ebec, Quebec, Canada Accepted 16 October 2005 Abstract Objective: To assess the validity of VEINES-QOL/Sym, a patient-reported questionnaire to evaluate quality of life and symptoms in patients with deep venous thrombosis (DVT). Study Design and Setting: Psychometric study within the Venous Thrombosis Outcomes (VETO) Study, a prospective cohort study of long-term outcomes after DVT. A total of 359 English- and French-speaking patients with acute, objectively diagnosed DVT were recruited at seven hospitals in Quebec, Canada. The VEINES-QOL/Sym questionnaire, a 26-item patient-reported measure that generates separate summary scores for symptoms (VEINES-Sym) and quality of life (VEINES-QOL) was evaluated for acceptability, reliability, validity, and responsiveness in VETO Study subjects. Results: Standard psychometric tests confirmed the acceptability (missing data, item endorsement frequencies, floor and ceiling effects), reliability (internal consistency, item–total and inter-item correlations, test–retest), validity (content, construct, convergent, discriminant, known groups), and responsiveness to clinical change of the VEINES-QOL/Sym in patients with DVT. Conclusion: The VEINES-QOL/Sym is a practical and scientifically sound patient-reported measure of outcomes that was developed using gold-standard methods. VEINES-QOL/Sym is valid and reliable for use as a measure of quality of life and symptoms in patients with acute DVT and provides a rigorous tool to allow more comprehensive evaluation of outcomes in clinical trials and epidemiological studies of patients with DVT. Ó 2006 Elsevier Inc. All rights reserved. Keywords: Venous thromboembolism; Deep vein thrombosis; Quality of life; Questionnaire; Patient outcomes; Outcomes research 1. Introduction Deep venous thrombosis is a common clinical problem that is associated with substantial morbidity and mortality [1]. Studies of the natural history or treatment of venous thrombosis have traditionally evaluated clinical endpoints such as recurrence of venous thromboembolism. While such endpoints are important, they are limited in their ability to describe and quantify the impact of venous thrombosis on patient health and daily functioning. Quality of life, * Corresponding author. Tel.: 514-340-8222 ext. 4667; fax: 514-3407564. E-mail address: susan.kahn@mcgill.ca (S.R. Kahn). 0895-4356/06/$ – see front matter Ó 2006 Elsevier Inc. All rights reserved. doi: 10.1016/j.jclinepi.2005.10.016 by defining health in broader terms than morbidity and mortality alone, provides valuable information on burden of illness and is an important endpoint to consider when studying patients with venous thrombosis [2–5]. Assessment of quality of life should ideally include both generic and disease-specific measures that are reliable, valid, and responsive [2,3]. Generic measures allow comparison across populations of patients with different conditions, whereas disease-specific measures are more responsive in detecting treatment effects and changes over time in patients who have the same disease [3,6]. Recently, as part of the Venous Insufficiency Epidemiological and Economic Study (VEINES) [7], an international prospective cohort study to evaluate the epidemiology and 1050 S.R. Kahn et al. / Journal of Clinical Epidemiology 59 (2006) 1049–1056 outcomes of chronic venous disorders, our group developed and validated a venous-disease-specific quality of life measure for use in patients with chronic venous disease, the VEINES-QOL/Sym questionnaire [8]. For the present study, we performed a comprehensive psychometric evaluation of the VEINES-QOL/Sym questionnaire in an independent sample of patients with acute deep venous thrombosis. (The VEINES-QOL/Sym questionnaire is available with the on-line version of this article at http:// www.elsevier.com/locate/jclinepi.) 2. Methods 2.1. Questionnaire development The VEINES-QOL/Sym is a patient-based questionnaire designed for self-completion. The content and format of questionnaire items and response scales were modeled after the SF-36 [9,10]. Generic SF-36 questions were modified to make them specific to venous disease, and new venous-disease-specific questions were developed using the same format and response scales of the SF-36. The questionnaire was developed in English and was then translated into French, French Canadian (for use with French-speaking patients in Canada), and Italian. The development of the questionnaire content, translation procedures, independent expert review, pretesting with patients, and psychometric evaluation in patients with chronic venous disease are described in detail elsewhere [8]. 2.2. VEINES-QOL/Sym questionnaire The 26-item questionnaire measures the impact of deep venous thrombosis on symptoms and quality of life from the patient’s perspective. The items cover symptoms (10 items), limitations in daily activities (9 items), time of day of greatest intensity (1 item), change over the past year (1 item), and psychological impact (5 items). Responses are rated on two-point to seven-point Likert response scales of intensity, frequency, or agreement. The time frame for questions about symptoms, daily limitations, and psychological impact covers the previous 4 weeks, as in the SF-36. 2.3. Scoring the VEINES-QOL/Sym Two summary scores can be computed. The VEINESQOL summary score (25 items) provides an estimate of the overall impact of deep venous thrombosis on the patient’s quality of life. The VEINES-Sym summary score (10 items) measures symptom severity. This includes nine venous symptoms (heavy legs, aching legs, swelling, night cramps, heat or burning sensation, restless legs, throbbing, itching, tingling sensation), rated on a five-point Likert scale of frequency (every day, several times a week, about once a week, less than once a week, never), and leg pain rated on a six-point scale of intensity (very severe, severe, moderate, mild, very mild, none). One item that asks about the time of day that the leg problem is most intense is not included in the summary scores; it provides descriptive information only, which may be of use in epidemiological research. For both the VEINES-QOL and VEINES-Sym scales, high scores indicate better outcomes. The VEINES-QOL/ Sym uses the standard method that is routinely used [11] for scoring questionnaires with items with different response scales [12]. Raw scores are first transformed to z-score equivalents (mean, 0; standard deviation, 1), which are then transformed to T-scores (mean, 50; standard deviation, 10) to give an easily understood range of scores. Scores for missing data are imputed using the same algorithm recommended for scoring the SF-36 [9,10]. A person-specific estimate is imputed for any missing item in cases where the patient answered >50% of the items in the scale. A copy of the VEINES-QOL/Sym and the SAS scoring program can be obtained from the corresponding author. 2.4. Validation of the VEINES-QOL/Sym in deep vein thrombosis: the Venous Thrombosis Outcomes study The Venous Thrombosis Outcomes (VETO) study is an ongoing, multicenter prospective cohort study with 5-year follow-up that we are conducting at seven hospital centers in the province of Quebec, Canada. Its objectives are to estimate the incidence and timing of development of the postthrombotic syndrome (PTS) after deep venous thrombosis, to identify clinical and genetic risk factors that predict its development, to measure the impact of deep venous thrombosis on quality of life, and to evaluate resource utilization and costs associated with deep venous thrombosis. An additional, prespecified objective was to assess the psychometric properties of the VEINES-QOL/Sym questionnaire for the evaluation of quality of life and symptoms in patients with deep venous thrombosis. 2.4.1. Patients During the study recruitment phase, all consecutive patients with objectively diagnosed, acute deep venous thrombosis at the seven hospital centers were screened for eligibility to participate in the VETO Study. The diagnosis of deep venous thrombosis was based on a venous duplex ultrasonography showing lack of compressibility or intraluminal thrombus in the affected vein [13,14] or on a contrast venogram showing a constant intraluminal filling defect in at least two different projections [15]. Patients were eligible to participate if they could read and understand English or French. Patients were excluded if they were incapable of responding to a questionnaire, had geographic inaccessibility that prevented return for the follow-up visits, had an expected lifespan of !3 months, or were unable or refused to provide informed consent. Ethics approval was obtained from the relevant committees in each hospital center and written informed consent was obtained from all patients prior to study entry. S.R. Kahn et al. / Journal of Clinical Epidemiology 59 (2006) 1049–1056 2.4.2. Study procedures From April 2001 to July 2002, 359 patients were enrolled in the VETO Study. To obtain data for the psychometric analysis, study patients were evaluated at clinic visits that took place at the time of enrollment (baseline) and at 1 and 4 months. At each clinic visit, patient-reported symptoms and quality of life were assessed using the appropriate language version (i.e., English or French Canadian) of the SF-36 [9,10] and of the VEINES-QOL/Sym [8]. The SF-36 questionnaire produces two summary scores: a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS), which reflect physical and mental health status, respectively. The VEINES-QOL/ Sym questionnaire produces two summary scores, VEINES-QOL and VEINES-Sym, which reflect venous disease-specific quality of life and venous symptoms, respectively. At each visit, patients provided information on changes in their health and underwent a standardized clinical assessment for the PTS, using a clinical scale developed by Villalta et al. [16]. This scale grades the severity, from 0 to 3, of each of five symptoms (pain, cramps, heaviness, pruritus, and paresthesia) and six signs (edema, skin induration, hyperpigmentation, venous ectasia, redness, pain during calf compression). A score of >5 indicates PTS and a score of >15 or the presence of a venous ulcer indicates severe PTS. 2.4.3. Psychometric Evaluation of the VEINES-QOL/ Sym We used gold-standard psychometric tests and criteria to evaluate the acceptability, reliability, validity, and responsiveness of VEINES-QOL/Sym scores [8,9,12,17]. Acceptability affects the quality of the data obtained, and was assessed by examining completeness of data and score distributions. Criteria for acceptability included !5% missing data for summary scores, even distribution of endorsement frequencies across response categories, and !10% floor and ceiling effects for summary scores. Reliability was assessed by measuring internal consistency and test–retest reliability. Internal consistency refers to the extent to which items comprising the scale measure the same construct (i.e., homogeneity of scale), and was assessed by Cronbach’s a [18] (should be O0.70 for summary scores) and item–total correlations (should be O0.20) [17]. Test–retest reliability, an indicator of the stability of a measuring instrument, was assessed by administering the instrument to respondents on two different occasions and examining the correlation between test and retest scores. The length of the test–retest interval should be short enough to ensure that clinical change in the symptom being measured is unlikely to occur, but sufficiently long to ensure that respondents do not recall their responses from first assessment. The test–retest interval in this study was 14 days. Test–retest reliability correlations for summary scores should be O0.80 [17]. 1051 Content validity refers to the extent to which the content of a scale is representative of the conceptual domain it is intended to cover, namely venous thrombosis, and was assessed qualitatively through pretesting with patients, expert opinion and literature review. Construct validity is shown by within-scale analyses and analyses against external criteria. Within-scale analyses should show evidence that a single entity (construct) is being measured and that items can be combined to form a summary score. This was assessed on the basis of evidence of good internal consistency (Cronbach’s a O 0.70) and a high correlation between VEINESQOL and VEINES-Sym scores (which purport to measure related aspects of outcome). Analyses against external criteria included (a) convergent validity, (b) discriminant validity, and (c) knowngroups differences. Convergent validity is shown by evidence that the scale is correlated with other measures of same or similar constructs, and assessed on the basis of correlations between VEINES-QOL/Sym and SF-36 scores. Correlations are expected to vary according to the similarity of the constructs being measured by each instrument. Both VEINES-QOL and SF-36 assess quality of life, so the two measures should be correlated, but because VEINES-QOL and SF-36 differ in being disease-specific vs. generic measures, correlations were expected to be in the moderate range (|0.5) [19]. VEINES-QOL/Sym items tap more physical than mental aspects, so higher correlations were expected with SF-36 PCS (physical) score than with MCS (mental) score. Finally, higher correlations were expected between VEINES-QOL and SF-36 than between VEINES-Sym and SF-36, because there is less overlap in content between the latter two. Discriminant validity is assessed by demonstrating that the scale is not correlated with other measures of different constructs. For example, low correlations were expected between VEINES-QOL/Sym scores and age and sex. Known-groups differences addresses the scale’s ability to differentiate known groups. This was assessed by comparing VEINES-QOL/Sym scores for patients who differed in severity of disease (as indicated by the Villalta PTS score). VEINES-QOL/Sym scores should decrease with increasing severity of disease. Responsiveness refers to the ability of a scale to detect clinically important change over time. The standard method for evaluating responsiveness is in the context of an intervention study, where pre- and posttreatment change scores are used to determine effect sizes. The VETO Study is a cohort study with no systematic intervention component, so we assessed responsiveness by calculating effect sizes [20,21] and standardized response means [22] for change in VEINES-QOL/Sym scores from 1 month to 4 months. Effect size was calculated as the mean change score from 1 month to 4 months divided by the standard deviation of scores at the 1-month assessment. This permits translation of before-and-after changes into a standard unit of 1052 S.R. Kahn et al. / Journal of Clinical Epidemiology 59 (2006) 1049–1056 measurement, rather than comparing raw score changes [20]. The standardized response mean is a variant of the effect size [22] and was calculated as the mean change score from 1 month to 4 months divided by the standard deviation of the change score. Effect size statistics and standardized response means were compared in patients defined as clinically improved or unimproved according to change Villalta PTS score [16] during the same time period. Effect sizes and standardized response means of 0.20 were defined as small, 0.50 as moderate, and >0.80 as large [20]. To compare the responsiveness of the disease-specific VEINESQOL/Sym with that of a generic measure, we used the same methods to evaluate responsiveness of SF-36 PCS and MCS scores. 2.4.4. Study samples for psychometric evaluation Acceptability of the questionnaire was assessed in the full sample of 359 patients. Reliability and validity analyses were carried out in all VETO patients who provided scorable VEINES-QOL/Sym and SF-36 questionnaires (<20% missing data) at the baseline clinic visit. This sample included 357 patients. Test–retest reliability was evaluated in 52 VETO study patients at two of the study centers for reasons of convenience (Jewish General Hospital, 19 English-speaking and 6 French-speaking patients; H^opital Maisonneuve-Rosemont, 27 French-speaking patients). After completing the VEINES-QOL/Sym questionnaire at the 4-month clinic visit, patients completed the questionnaire again within a 2-week interval and mailed it to the study center. Responsiveness was evaluated in all VETO patients who satisfied two criteria: (i) !20% missing data on the VEINES-QOL/Sym and (ii) data available for both patient-reported outcomes (i.e., quality of life questionnaires) and clinical outcome (i.e., PTS score) for both the 1-month and 4-month clinic visits. The responsiveness sample included 303 patients; most exclusions were due to missed 1- or 4-month clinic visits, with only 2 patients excluded because of O20% missing VEINES-QOL/Sym data. 3. Results 3.1. VETO Study patient characteristics Table 1 gives the baseline characteristics of VETO Study patients. Half of the patients were male, the mean age was 56 years, and two-thirds were outpatients. Deep venous thrombosis was located in proximal venous segments in 55% and in distal (infrapopliteal) segments in 45%. Concurrent symptomatic pulmonary embolism was present in 15% of patients, and a history of previous deep venous thrombosis was documented in 22% of patients. 3.2. Psychometric properties Results are reported separately for VEINES-QOL and VEINES-Sym scores. Table 1 Baseline patient characteristics (N 5 359) Characteristic Value Male, no. (%) Age, years Mean (SD) Range Patient location, no. (%) Inpatient Outpatient Highest level of education, no. (%) No schooling Primary school High school College or university Not employeda, no. (%) BMI, kg/m2, mean (SD) VTE Risk Factorsb, no. (%) Surgery Trauma Immobilization Active cancer Estrogenic drugs Pregnancy Type of DVT, no. (%) Proximal Distal Concurrent pulmonary embolism Prior history of VTE, no. (%) Current smoker, no. (%) 180 (50.1) 55.8 (14.8) 21–95 117 (32.6) 242 (67.4) 2 34 123 200 173 27.7 (0.6) (9.5) (34.3) (55.7) (48.3) (6.0) 100 62 79 45 83 8 (28.1) (17.3) (22.1) (12.5) (23.1) (2.2) 197 162 54 78 66 (54.9) (45.1) (15.2) (21.7) (18.4) Abbreviations: BMI, body mass index; DVT, deep venous thrombosis; SD, standard deviation; VTE, venous thromboembolism. a Includes retired, student, homemaker, unemployed. b Some patients had O1 risk factor. 3.2.1. Acceptability The VEINES-QOL/Sym questionnaire took 10–15 minutes to complete and showed good acceptability in the VETO study population. Table 2 reveals a low proportion of missing data and low floor and ceiling effects. Examination of item endorsement frequencies (results not shown) revealed that responses for all items were evenly (more or less uniformly) distributed across response categories, with no floor or ceiling effects. 3.2.2. Internal consistency reliability Cronbach’s a coefficients [18] indicate high internal consistency (Table 2). Values exceed the standard criterion of 0.70. All item–total correlations satisfied the criterion of O0.20, ranging from 0.37 to 0.70 for the VEINES-QOL and from 0.45 to 0.77 for the VEINES-Sym (data not shown for individual items). 3.2.3. Test–retest reliability The correlations between test and retest scores were high, indicating good test–retest reliability (Table 2). All intraclass correlation coefficients were O0.85. 3.2.4. Content validity Content validity was evaluated during the phase of development of the questionnaire. Evidence from pretesting 1053 S.R. Kahn et al. / Journal of Clinical Epidemiology 59 (2006) 1049–1056 Table 2 Acceptability and reliability of the VEINES-QOL/Sym Value Missing data, % (N 5 359) VEINES-QOL VEINES-Sym Floor effects, % (N 5 357) VEINES-QOL VEINES-Sym Ceiling effects, % (N 5 357) VEINES-QOL VEINES-Sym Internal consistency: Cronbach’s a (N 5 357) VEINES-QOL VEINES-Sym Test–retest reliability: ICCa VEINES-QOL VEINES-Sym 1 1 !1 !1 !1 8 0.91 0.88 0.87 0.87 Abbreviations: ICC, Intraclass correlation coefficient. a Test–retest analyses performed on 52 patients at two centers. with patients, expert opinion, and a review of literature supports the content validity of the VEINES-QOL/Sym [8]. 3.2.5. Construct validity (within-scale analyses) Evidence of high internal consistency supports the construct validity of the VEINES-QOL/Sym. High a coefficients (Table 2) and moderately high item–total correlations indicate that a single construct is being measured and that the items can be combined to form summary scores. A high intercorrelation between VEINES-QOL and VEINES-Sym scores (r 5 0.88) supports the convergent validity of the two scales. 3.2.7. Construct validity (discriminant validity) Low correlations between the VEINES-QOL and VEINES Sym and age and sex (all correlations <0.15) (Table 3) support the discriminant validity of both scales and suggest that responses to the VEINES-QOL/Sym are not biased in terms of age or gender. 3.2.8. Construct validity (known group differences) Table 4 gives the mean VEINES-QOL/Sym scores for patients classified by Villalta PTS score obtained at the 1-month clinic visit. As hypothesized, VEINES-QOL and VEINES-Sym scores show the expected gradient of poorer outcome with increasing severity of PTS. 3.2.9. Responsiveness Table 5 gives the results of the responsiveness analysis of the VEINES-QOL/Sym and SF-36. Among patients whose PTS scores improved from 1 month to 4 months, larger effect sizes were observed for the VEINES-QOL (0.77), VEINES-Sym (0.65) and SF-36 PCS (0.60) than for SF-36 MCS (0.38). Hence, VEINES-QOL is the most responsive, VEINES-Sym and SF-36 PCS show similar responsiveness, and the SF-36 MCS is the least responsive to change. In contrast, among patients without improvement in PTS scores, effect sizes for all measures were small. The standardized response mean showed similar patterns. Results therefore demonstrate that the VEINES-QOL and VEINES-Sym are both highly responsive to clinical change, indicating that VEINES-QOL and VEINES-SYM successfully discriminate between clinically improved and unimproved patients. 4. Discussion 3.2.6. Construct validity (convergent validity) Table 3 gives the correlations between the VEINESQOL/Sym and the SF-36. All correlations support our hypotheses. The VEINES-QOL/Sym is moderately correlated with SF-36 PCS and MCS summary scores. Correlations between the VEINES-QOL and SF-36 are higher for PCS (physical health status) than MCS (mental health status) scores. Correlations with the SF-36 are higher for the VEINES-QOL than for the VEINES-Sym. Table 3 Convergent and discriminant validity of the VEINES-QOL/Sym (N 5 357) Correlation, r Other measures SF-36 physical (PCS) SF-36 mental (MCS) Patient characteristics Age Sex VEINES-QOL VEINES-Sym 0.63 0.37 0.49 0.29 0.06 0.15 0.03 0.12 The results of our prospective psychometric evaluation of the VEINES-QOL/Sym questionnaire indicate that it meets standard, accepted criteria of acceptability, reliability, validity, and responsiveness for use as a patientreported measure of outcome in deep venous thrombosis. The VEINES-QOL/Sym questionnaire is available in four language versions, is quick and easy to administer, and can be easily incorporated into epidemiological studies Table 4 Known-group differences validity as mean VEINES-QOL/Sym scores by PTS score at 1 month (N 5 328) Scorea, mean (SD) Scoreb, PTS N VEINES-QOL VEINES-Sym 0–4 5–14 >15 175 145 8 52.0 (4.9) 47.9 (5.5) 42.1 (5.3) 52.9 (4.6) 48.2 (5.6) 40.6 (6.6) Of the original 359 VETO patients, 31 did not attend the 1-month visit. Abbreviations: PTS, postthrombotic syndrome; SD, standard deviation. a Higher scores indicate better outcomes. b Higher scores indicate more severe disease. 1054 S.R. Kahn et al. / Journal of Clinical Epidemiology 59 (2006) 1049–1056 Table 5 Responsiveness of the VEINES-QOL/Sym in patients with deep vein thrombosis QOL score, mean (SD) PTS scores improved VEINES-QOL VEINES-Sym SF-36 PCS SF-36 MCS PTS scores did not improve VEINES-QOL VEINES-Sym SF-36 PCS SF-36 MCS 1 to 4 mo change N 1 mo 4 mo Change Effect sizea SRMa 158 158 158 158 49.6 50.0 36.9 46.5 (5.6) (5.9) (11.0) (12.1) 54.0 53.8 43.5 51.0 (5.2) (5.1) (11.4) (10.3) 4.3 3.8 6.6 4.6 (4.3) (4.8) (10.5) (11.2) 0.77 0.65 0.60 0.38 1.0 0.79 0.63 0.40 142 142 145 144 50.3 50.9 39.2 45.5 (5.6) (5.6) (10.5) (11.9) 52.1 51.5 42.7 49.5 (6.0) (6.3) (11.8) (10.7) 1.9 0.5 3.4 3.9 (4.6) (5.4) (10.1) (10.2) 0.33 0.09 0.33 0.34 0.41 0.11 0.34 0.38 Mean scores, effect sizes, and standardized response means for change in VEINES-QOL/Sym and SF-36 scores between 1-month and 4-month assessments, according to improvement or lack of improvement in PTS scores. Positive change scores indicate improvement in quality of life. Abbreviations: MCS, mental component summary; PCS, physical component summary; PTS, postthrombotic syndrome; SRM, standardized response mean; Sym, symptom portion of VEINES. a Effect sizes and standardized response means of 0.20 are defined as small, 0.50 as moderate, and >0.80 or greater as large [20]. and clinical trials of new drug treatments, thus providing a rigorous method for improving the evaluation of outcomes in studies of patients with deep venous thrombosis. Deep venous thrombosis is associated with significant disease burden in terms of pain and suffering, loss of mobility, impairment of function at work and at home, and psychological distress [23]. Research on these important patient-reported outcomes has been limited by the lack of practical, scientifically rigorous outcome measures. To date, some studies have evaluated quality of life in patients with deep venous thrombosis using generic measures alone [24,25]. Generic measures, however, do not give a full picture of the impact of deep venous thrombosis on quality of life and are less useful than disease-specific measures in evaluating change over time. A number of disease-specific quality of life instruments intended for use in patients with deep venous thrombosis have been proposed, but none have fully met standard criteria for validity, reliability and responsiveness. Van Korlaar et al. [26] developed a measure of venous thrombosis-related quality of life that was evaluated at a single time point in 45 retrospectively identified patients with previous deep venous thrombosis at one hospital center. The measure showed evidence of good internal consistency reliability and validity, but responsiveness and test–retest reliability have not been evaluated, and individual venous symptoms were not considered. Mathias et al. [27] developed a disease-specific quality of life measure intended for use in patients with iliofemoral deep venous thrombosis; this measure was derived from the Health Utilities Index and SF-12 measures, with the addition of new items specific for deep venous thrombosis. In a population of 111 retrospectively identified patients with prior iliofemoral deep venous thrombosis, this measure demonstrated acceptable reliability and validity but limited responsiveness. Hedner et al. [28] reported on a Swedish language, 29item instrument for measuring quality of life in patients with deep venous thrombosis; it also includes specific items that relate to burden of treatment with warfarin. Consecutive outpatients with proximal deep venous thrombosis completed the questionnaire at one point in time. There is evidence for internal consistency and construct validity, but test–retest reliability and responsiveness have not been assessed. Finally, Hudgens et al. [29] recently reported the development and validation of a 14-item leg symptom index intended for monitoring of DVT-related symptoms, rated separately in each leg. The measure was administered by telephone interview to 77 patients (age and sex distribution not reported) at 3–7 days, 30–40 days, and 12 months after hospitalization for acute deep venous thrombosis. There is evidence of internal consistency and validity, but test–retest reliability and responsiveness have not been reported. The VEINES-QOL/Sym has potential applications in both research and routine monitoring of health care. As a more responsive instrument than the SF-36, the VEINES-QOL/Sym holds promise in evaluating new treatments for deep venous thrombosis, whose effects may not be detected by less sensitive generic measures. As an outcome measure in clinical trials, VEINES-QOL/Sym will provide scientifically robust information about the efficacy of treatment from the patient’s point of view. This information, when combined with data on clinical outcomes and costs, will allow comprehensive evaluation of new treatments. The VEINES-QOL/Sym measure offers flexibility, because it provides a validated measure of both deep venous thrombosis-related quality of life and deep venous thrombosis-related symptoms. Although DVT treatment-related issues (e.g., blood test monitoring while on warfarin) may indeed have an impact on quality of life, the objective of the VEINES-QOL measure is to evaluate the impact of S.R. Kahn et al. / Journal of Clinical Epidemiology 59 (2006) 1049–1056 the condition, not its specific treatment, on quality of life. As such, it is flexible for use in a broad range of situations, and permits comparability of studies that use different treatments or interventions. Our conclusions about the acceptability, reliability, validity, and responsiveness of the VEINES-QOL/Sym are based on a sample of patients with objectively diagnosed symptomatic deep venous thrombosis recruited and prospectively followed at seven hospital centers. Our sample is likely to be representative, given that our study was multicenter, both inpatients and outpatients were enrolled, and inclusion criteria were broad. Nevertheless, future work should be undertaken to establish population norms for VEINES-QOL and VEINES-Sym scores in deep venous thrombosis patients in different countries, so that the appropriate population-based weights can be used in place of current sample-specific scoring algorithms. In addition, further evaluation of the ability of the VEINES-QOL/Sym measure to detect change following different treatments for deep venous thrombosis would provide additional useful evidence of responsiveness to specific interventions. Finally, testing of the VEINES-QOL/Sym measure in independent samples of patients with deep venous thrombosis would be useful to confirm its psychometric properties. In conclusion, our results indicate that VEINES-QOL/ Sym is a practical, reliable, valid and responsive measure of quality of life and symptoms in patients with deep venous thrombosis. Use of this measure in clinical trials and epidemiological studies of patients with deep venous thrombosis will allow more comprehensive evaluation of patient outcomes and burden of illness than is currently provided using clinical endpoints alone. Acknowledgments This study was conducted as part of the VETO Study, a research program on long-term outcomes after venous thrombosis supported by the Fonds de la Recherche en Sante du Quebec and by an unrestricted grant from Sanofi Synthelabo. Drs. Kahn and Shrier are recipients of Clinical Investigator Awards from the Fonds de la Recherche en Sante du Quebec, and Dr. Johri is a recipient of an Investigator Award from the Fonds de la Recherche en Sante du Quebec. We thank the VETO study personnel at the clinical study sites for their dedication to this project. References [1] Bates SM, Ginsberg JS. Treatment of deep-vein thrombosis. N Engl J Med 2004;351:268–77. [2] Lamping DL. Measuring health-related quality of life in venous disease: practical and scientific considerations. Angiology 1997;48:51–7. [3] Patrick DL, Deyo RA. Generic and disease-specific measures in assessing health status and quality of life. Med Care 1989;27(3 Suppl):S217–32. 1055 [4] Kahn SR, Solymoss S, Lamping DL, Abenhaim L. Long-term outcomes after deep vein thrombosis: postphlebitic syndrome and quality of life. J Gen Intern Med 2000;15:425–9. [5] van Korlaar I, Vossen C, Rosendaal F, Cameron L, Bovill E, Kaptein A. Quality of life in venous disease. Thromb Haemost 2003;90:27–35. [6] Wiebe S, Guyatt G, Weaver B, Matijevic S, Sidwell C. Comparative responsiveness of generic and specific quality-of-life instruments. J Clin Epidemiol 2003;56:52–60. [7] Abenhaim L, Kurz X. The VEINES study (VEnous INsufficiency Epidemiologic and Economic Study): an international cohort study on chronic venous disorders of the leg. Angiology 1997;48:59–66. [8] Lamping DL, Schroter S, Kurz X, Kahn SR, Abenhaim L. Evaluating outcomes in chronic venous disorders of the leg: development of a scientifically rigorous, patient-reported measure of symptoms and quality of life. J Vasc Surg 2003;37:410–9. [9] Ware JE, Snow KK, Kosinski MA, Gandek B. SF-36 Health Survey: Manual and interpretation guide. Boston, MA: The Health Institute, New England Medical Center; 1993. [10] Ware JE, Kosinski M, Keller SD. SF-36 physical and mental summary measures: a user’s manual. Boston, MA: The Health Institute, New England Medical Center; 1994. [11] Ware J, Kosinski M. SF-36 physical and mental health summary scores: a manual for users of version 1. 2nd ed. Lincoln, RI: QualityMetric; 2001. [12] Streiner DL, Norman GR. Health measurement scales: A practical guide to their development and use. 2nd ed. Oxford: Oxford University Press; 1995. [13] Lensing AWA, Prandoni P, Brandjes DPM, Huisman PM, Vigo M, Tomasella G, Krekt J, Wouter Ten Cate J, Huisman MV, Buller HR. Detection of deep vein thrombosis by real-time B mode ultrasonography. N Engl J Med 1989;320:342–5. [14] Kearon C, Ginsberg JS, Hirsh J. The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Ann Intern Med 1998;129:1044–9. [15] Lensing AWA, Buller HR, Prandoni P, Batchelor D, Molenaar AH, Cogo A, Vigo M, Huisman PM, ten Cate JW. Contrast venography, the gold standard for the diagnosis of deep vein thrombosis: improvement in observer agreement. Thromb Haemost 1992;67:8–12. [16] Villalta S, Bagatella P, Piccioli A, Lensing A, Prins M, Prandoni P. Assessment of validity and reproducibility of a clinical scale for the post-thrombotic syndrome. Haemostasis 1994;24:158a. [Abstract]. [17] Nunnally JC, Bernstein IH. Psychometric theory. 3rd ed. New York: McGraw-Hill; 1994. [18] Cronbach L. Coefficient alpha and the internal structure of tests. Psychometrika 1951;16:297–334. [19] Colton T. Statistics in medicine. 1st ed. Boston, MA: Little, Brown; 1974. 210–1. [20] Cohen J. Statistical power analysis for the behavioral sciences. Revised ed. New York: Academic Press; 1977. [21] Kazis LE, Anderson JJ, Meenan RF. Effect sizes for interpreting changes in health status. Med Care 1989;27(3 Suppl):S178–89. [22] Liang MH, Fossel AH, Larson MG. Comparisons of five health status instruments for orthopedic evaluation. Med Care 1990;28:632–42. [23] Kahn SR, Ginsberg JS. Relationship between deep venous thrombosis and the postthrombotic syndrome. Arch Int Med 2004;164: 17–26. [24] Beyth RJ, Cohen AM, Landefeld CS. Long-term outcomes of deepvein thrombosis. Arch Intern Med 1995;155:1031–7. [25] O’Brien B, Levine M, Willan A, Goeree R, Haley S, Blackhouse G, Gent M. Economic evaluation of outpatient treatment with low-molecular-weight heparin for proximal vein thrombosis. Arch Intern Med 1999;159:2298–304. [26] Van Korlaar IM, Vossen CY, Rosendaal FR, Bovill EG, Cushman M, Naud S, Kaptein AA. The impact of venous thrombosis on quality of life. Thromb Res 2004;114:11–8. 1056 S.R. Kahn et al. / Journal of Clinical Epidemiology 59 (2006) 1049–1056 [27] Mathias SD, Prebil LA, Putterman CG, Chmiel JJ, Throm RC, Comerota AJ. A health-related quality of life measure in patients with deep vein thrombosis: a validation study. Drug Inf J 1999;33: 1173–87. [28] Hedner E, Carlsson J, Kulich KR, Stigendal L, Ingelgard A, Wiklund I. An instrument for measuring health-related quality of life in patients with deep venous thrombosis (DVT): development and validation of Deep Venous Thrombosis Quality of Life (DVTQOL) questionnaire. Health Qual Life Outcomes 2004;2:30. [29] Hudgens S, Cella D, Caprini C, Caprini J. Deep vein thrombosis: validation of a patient-reported leg symptom index. Health Qual Life Outcomes 2003;1:76. S.R. Kahn et al. / Journal of Clinical Epidemiology 59 (2006) 1049–1056 1056.e1 VEINES-QOL/Sym QUESTIONNAIRE You have had a venous thrombosis. In this survey, we are interested in finding out more about the effects of your leg problem on your daily activities, both at home and at work. This information will give us a better idea about how to treat such problems. Thank you for participating in this study. This questionnaire includes questions about your health in general and about your leg problem, as well as questions about your life and usual activities. It will take about 10 minutes to complete. All of your answers are confidential. Do not write your name on the questionnaire. Thank you for your help. 1056.e2 S.R. Kahn et al. / Journal of Clinical Epidemiology 59 (2006) 1049–1056 INSTRUCTIONS HOW TO ANSWER: Answer every question by marking the answer as indicated. If you are unsure about how to answer a question, please give the best answer you can. These questions are about your leg problem(s). 1. During the past 4 weeks, how often have you had any of the following leg problems? (check one box on each line) Every day Several times a week About once a week Less than once a week Never 1. Heavy legs 1 2 3 4 5 2. Aching legs 1 2 3 4 5 3. Swelling 1 2 3 4 5 4. Night cramps 1 2 3 4 5 5. Heat or burning sensation 1 2 3 4 5 6. Restless legs 1 2 3 4 5 7. Throbbing 1 2 3 4 5 8. Itching 1 2 3 4 5 9. Tingling sensation (e.g.pins and needles) 1 2 3 4 5 2. At what time of day is your leg problem most intense ? (check one) 1 On waking 4 During the night 2 At mid-day 5 At any time of day 3 At the end of the day 6 Never 3. Compared to one year ago, how would you rate your leg problem in general now? (check one) 1 Much better now than one year ago 4 Somewhat worse now than one year ago 2 Somewhat better now than one year ago 5 Much worse now than one year ago 3 About the same now as one year ago 6 I did not have any leg problem last year 1056.e3 S.R. Kahn et al. / Journal of Clinical Epidemiology 59 (2006) 1049–1056 4. The following items are about activities that you might do in a typical day. Does your leg problem now limit you in these activities? If so, how much ? (Check one box on each line) I do not work YES, Limited A Lot YES, Limited A Little NO, Not Limited At All a. Daily activities at work b. Daily activities at home (e.g. housework, ironing, doing odd jobs repairs around the house, gardening, etc...) c. Social or leisure activities in which you are standing for long periods (e.g. parties, weddings, taking public transportation, shopping, etc...) d. Social or leisure activities in which you are sitting for long periods (e.g. going to the cinema or the theater, travelling, etc...) 5. During the past 4 weeks, have you had any of the following problems with your work or other regular daily activities as a result of your leg problem? 0 1 2 3 1 2 3 1 2 3 1 2 3 (check one box on each line) YES NO a. Cut down the amount of time you spent on work or other activities 1 2 b. Accomplished less than you would like 1 2 c. Were limited in the kind of work or other activities 1 2 d. Had difficulty performing the work or other activities (for example, it took extra effort) 1 2 6. During the past 4 weeks, to what extent has your leg problem interfered with your normal social activities with family, friends, neighbors or groups? (check one) 1 Not at all 4 Quite a bit 2 Slightly 5 Extremely 3 Moderately 7. How much leg pain have you had during the past 4 weeks? (check one) 1 None 4 Moderate 2 Very mild 5 Severe 3 Mild 6 Very severe 1056.e4 8. S.R. Kahn et al. / Journal of Clinical Epidemiology 59 (2006) 1049–1056 These questions are about how you feel and how things have been with you during the past 4 weeks as a result of your leg problem. For each question, please give the one answer that comes closest to the way you have been feeling. How much of the time during the past 4 weeks - (check one box on each line) A Good A Little All of Most of Some of of the None of Bit of the Time the Time the Time the Time Time the Time a. Have you felt concerned about the appearance of your leg(s) ? 1 2 3 4 5 6 b. Have you felt irritable ? 1 2 3 4 5 6 c. Have you felt a burden to your family or friends ? 1 2 3 4 5 6 d. Have you been worried about bumping into things ? 1 2 3 4 5 6 e. Has the appearance of your leg(s) influenced your choice of clothing ? 1 2 3 4 5 6 Thank you for your help. Please write today’s date: _____/_____/_______ (day month/year)