Inclusion and exclusion

Consecutive patients with new referral for evaluation of peripheral arterial disease (IC or CLI) at the vascular surgery department at two different hospitals (H1 and H2) were invited to participate based on the information given by the referring physician. The inclusion period ran from August 2014 to August 2015. Patients received written information about the study and the two questionnaires, VQ-6 and SF-36, by post before the scheduled appointment at the outpatient clinic. If the patients failed to bring the questionnaires or were admitted acutely, they were invited to participate at site and completed the questionnaires before further investigations. The returned questionnaires were not available to the treating physician.

If the consulting vascular surgeon ruled out symptomatic PAD, the patients were excluded. For the patients who died, underwent major amputation or major non-vascular surgery, or moved out of the hospital region, only baseline data was available. Patients also had the opportunity to withdraw at all times. Inclusion, exclusion and follow-up of patients are shown in Fig. 1.

Fig. 1 Inclusion and exclusion of patients in the VascuQoL-6 study. PAD –Peripheral arterial disease, IC-intermittent claudication, CLI –critical limb ischemia Full size image

Work up

In the vascular laboratory, arterial pressures were measured with a hand held Doppler device (H1: Model 811-BTS (9.5 MHz) Parks medical electronics INC, Aloha, Oregon, USA, H2: Model 811-BTS (8.2 MHz) Parks medical electronics INC, Aloha, Oregon, USA), and the ankle-brachial index (ABI) was calculated. Patients with claudication were tested on a constant load treadmill with a speed of 2.5 km/h and no inclination (H1: Abilica X-fit 1, Myrnasport, Norway, H2: Woodway PPS Med, Woodway GmbH, D79576 Weil am Rhein, Germany). A post-exercise ABI drop exceeding 0.1 was regarded significant. Intermittent claudication distance (ICD) and maximum walking distance (MWD) were registered in meters. There is a ceiling effect at 416 m, as the test was terminated after 10 min for all patients.

Risk factors, comorbidity, medication and Fontaine classification [15] were registered by the vascular surgeon during the clinical consultation.

Follow-up

All patients were scheduled for a new consultation with completion of questionnaires, arterial pressure measurements, treadmill-test and clinical evaluation. Patients receiving conservative treatment (information about the disease, the value of walking exercise and medical treatment) and patients referred for supervised exercise therapy were followed up after 4 weeks. The referral algorithm for imaging and invasive treatment was unaltered from usual practice. If results from imaging indicated a conservative approach, the patients had their follow-up as soon as possible. Patients referred for invasive treatment (endovascular or surgical) underwent follow-up 4 weeks after the invasive procedure.

Translation and adaption of VascuQoL-6

The VQ-6 was translated to Norwegian from the Swedish version using the method of linguistic adaption and validation described by the MAPI institute [16], including a forward and backward translation to English. Face value of the questionnaire was tested by five patients and five experienced vascular surgeons, by interviews, answering three questions: Are the questions easy to understand? Do you find them relevant for your condition/your patients? Do you have any suggestions for alterations (language/missing items, scaling, etc.)? This evaluation resulted in a slight adjustment of wording. The final version was approved by the original developers.

Each of the six items scores from one to four, sum score range is from six to 24, and a higher score indicates better health.

SF-36

SF-36 (version 1) was chosen as generic QoL anchor, as this questionnaire has been used in prior validation of VascuQoL-25 [10, 11, 13, 17] and as QoL measure in a range of PAD studies [18,19,20,21]. This enabled comparison with earlier research. Subscale (PF –physical functioning, RP –physical role, BP –bodily pain, GH –general health, VT –vitality, SF -social functioning, RE –emotional role, MH –mental health) and component summary scoring (PCS –physical component score, MCS –mental component score) was performed using Qualimetric Health Outcomes Scoring Software 4.0, using the original scoring method [22]. This software uses the 1998 US norm population for calculation of component summary scores, as US norm has been recommended for western countries [23]. Data from the Norwegian norm population from 1998 [24] was used in Fig. 2 for illustration purposes.

Fig. 2 SF-36 subscale mean scores at baseline (n = 171). Patients suffering from intermittent claudication (IC) and critical limb ischemia (CLI). For comparison Norwegian norm population aged 60 years and over (Loge 1998). PF - physical functioning, RP - physical role limitations, BP - bodily pain, GH - general health, VT - vitality, SF - social functioning, RE - emotional role limitations, MH - mental health Full size image

The subscale scores of SF-36 range from 0 to 100, and the highest score indicates no health-related reduction of QoL. The component summary scores relates to the normative population (mean 50, SD 10), and a score lower than 50 indicates lower QoL than the normative population.

Power analysis

The power analysis was conducted for the responsivity to change after treatment. An evaluation of the practice at H1 showed that one third of patients referred with IC and most patients with CLI would receive invasive treatment. Registrations of invasive treatment from the Norwegian vascular registry (NORKAR- www.norkar.no) showed an approx. 15–18% proportion of CLI at H1. Earlier studies have shown 20–32% improvement in VascuQoL-25 summary score after invasive treatment [21, 25]. A 25% improvement would translate to a four point improvement in VQ-6 summary score and the strength evaluation was done with the aim to detect four points improvement for at least 30% of the invasive treatment group and less than 5% of the conservative treatment group.

Statistic methods

All statistics were calculated using Statistical Package for the Social Sciences version 21 (IBM/SPSS Inc., Armonk, NY, USA).

Reliability (internal consistency)

Cronbach’s alpha was calculated to evaluate the internal consistency of the VQ-6. A reliable health-related QoL-measure should center between 0.7 and 0.9 for group comparisons [26]. The intraclass correlation coefficient (ICC, two-way mixed model with 95% confidence interval, absolute agreement of average measures) was calculated to test-retest reliability for patients in the conservative treatment group, as a priori no health change was expected for this group in the short time span of 4 weeks.

Validity (accuracy)

Content validity was assessed through face value evaluation and through the earlier development processes [9, 12].

The construct validity (cross-sectional construct validity, sensitivity to differences) was assessed through the instrument’s ability to discriminate between patients suffering from IC and CLI, using Receiver operating characteristic (ROC) curve analysis, with the Fontaine classification as a basis. The area under the ROC curve (AUC) benchmarks were > 0.8 (excellent), 0.7–0.8 (fair) and < 0.7 (poor).

Criterion validation was performed through exploration of correlations between SF-36 domain and summary scores and VQ-6 sum scores, using Pearson product-moment correlation coefficient for normally distributed variables and Spearman’s rank correlation coefficient as a non-parametric alternative. Interpretation of correlation coefficients was done using Cohen’s criteria: small 0.1–0.29, medium 0.3–0.49 and large 0.5–1.0.

Standard and hierarchical linear multiple regressions were used to model the relationship between the questionnaires while controlling for other variables, after checking for violation of assumptions (statistical power, multicollinearity, singularity, outliers and normality).

Responsiveness

Change analysis was done using t-test for normally distributed continuous data, Wilcoxon signed rank test for non-parametric continuous data and McNemar’s test for dichotomous data.

ROC curves were calculated for comparison with clinical anchors of change.

Standardized response means (mean change divided by the standard deviation of the change) of SF-36 domains and component summary scores and all items and summary score of VQ-6 were calculated to evaluate responsiveness [27].

To determine the clinically important change in VQ-6, the minimally important difference (MID) was calculated using the distribution based method with 0.5 SD [28] as well as anchored in a clinical evaluation by the vascular surgeon [29].

Missing data

Analysis was performed using all available data at baseline and during follow-up. If only one item was missing for VQ-6 (3 patients) we did a single imputation using the median of the item score for all patients. One patient missed one item after treatment, and the sum score of VQ6 was omitted from analysis. For SF-36, imputation was done using the scoring software (Qualimetric Health Outcomes Scoring Software 4.0). The mean subscale score is used if the patient has answered more than half of the items in the domain.