Hitoshi Ishii & Eisei Oda

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1 Reproducibility and validity of a satisfaction questionnaire on hypoglycemic agents: the Oral Hypoglycemic Agent Questionnaire (OHA-Q) Hitoshi Ishii & Eisei Oda Diabetology International ISSN Volume 3 Number 3 Diabetol Int (2012) 3: DOI /s y 1 23

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3 Diabetol Int (2012) 3: DOI /s y ORIGINAL ARTICLE Reproducibility and validity of a satisfaction questionnaire on hypoglycemic agents: the Oral Hypoglycemic Agent Questionnaire (OHA-Q) Hitoshi Ishii Eisei Oda Received: 5 December 2011 / Accepted: 26 March 2012 / Published online: 1 August 2012 Ó The Japan Diabetes Society 2012 Abstract In order to assess satisfaction with treatment using oral hypoglycemic agents among patients with type 2 diabetes mellitus, we developed the Oral Hypoglycemic Agent Questionnaire (OHA-Q), a patient-administered questionnaire composed of 20 questions. We enrolled 597 outpatients with type 2 diabetes mellitus who had been treated with a single oral hypoglycemic agent for 1 month or longer at 45 institutions in Japan. Their physicians provided background information on the patients, etc., in the physician-filled forms, and the patients answered both OHA-Q and the Diabetes Treatment Satisfaction Questionnaire (DTSQ) twice in 1 week. After patients with incomplete forms, etc., had been excluded, statistical analyses were performed on 483 patients for the validity assessment and on 419 patients for the reproducibility assessment. Based on factor analysis of the OHA-Q item scores, a simple structure was obtained by three-factor varimax rotation, and three subscale scores were identified as the treatment convenience score, somatic symptom score and satisfaction score. All intraclass correlation coefficients for the subscale scores were 0.7 or higher, showing high reproducibility. A correlation of 0.4 or higher was observed between the subscale scores and the DTSQ satisfaction score. Moreover, an expected association was observed between the subscale scores and patient background factors. Based on these results, OHA-Q may have H. Ishii Department of Endocrinology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara , Japan E. Oda (&) Medical TOUKEI Corporation, Shinjuku Sumitomo Bld. 27F, Nishi-Shinjuku, Shinjuku-ku, Tokyo , Japan oda@md-stat.co.jp adequate reproducibility and validity as an assessment scale for satisfaction with treatment using oral hypoglycemic agents in patients with type 2 diabetes mellitus. Keywords Oral hypoglycemic agent Treatment satisfaction Questionnaire Reproducibility Validity Introduction: background and objectives For assessment of treatment in many disease areas, patientreported outcomes (PRO) are used in addition to objective measurements and assessment by health-care professionals, such as physicians [1]. Rating scales on treatment satisfaction, which is one PRO, are available in various areas, such as cancer [2 5]. Diabetes mellitus has the feature that the success of treatment largely depends on self-care by patients. Thus, treatment satisfaction for diabetes mellitus has more importance than a supplementary assessment to objective indices of glycemic control, such as hemoglobin A1c (HbA1c). In other words, low treatment satisfaction causes the patient to have low treatment compliance, leading to deterioration of glycemic control and increased risk of complications as a consequence. Because of this background, many assessment scales have been developed for treatment satisfaction in patients with diabetes mellitus. Representative examples include the Diabetes Quality of Life used in the Diabetes Control and Complications Trial (DCCT) [6], which is a large-scale clinical trial, the Diabetes Treatment Satisfaction Questionnaire (DTSQ), an assessment scale developed by Bradley [7, 8], the Problem Areas in Diabetes Survey, developed at the Joslin Diabetes Center [9], and the Insulin Therapy-Related Quality of Life (ITR-QOL), developed by Ishii et al. [10, 11].

4 Development of a satisfaction questionnaire on oral hypoglycemic agent 153 Oral hypoglycemic agents (OHA) have a history of more than 50 years since sulfonylurea (SU) compounds were introduced in the 1950s. At present, there are various options, including biguanides, a-glucosidase inhibitors, thiazolidine insulin sensitizers and the dipeptidyl peptidase IV (DPP-4) inhibitor, in addition to SU [12]. Because these agents differ in their dosages and adverse reactions, efficacy is not the only element to select the best agent for a patient, but comprehensive assessment including patient convenience and preferences is necessary for agent selection. Although the previously described DTSQ and ITR- QOL are assessment scales for treatment satisfaction in patients with diabetes mellitus, these scales are not designed to clarify differences among the oral therapeutic agents. Thus, they cannot provide information useful for the selection of oral therapeutic agents. Recently, an OHA-specific satisfaction questionnaire, SOADAS (Oral Anti-Diabetic Agent Scale), was developed and validated [13]. SOADAS is a six-item scale with uni-dimensional structure, focusing on concepts relevant to patient satisfaction with OHA, i.e., ability to control blood sugar and diabetic symptoms, how quickly the medication works, the medication s effect on weight, tolerability and overall satisfaction. SOADAS is well designed and easy to fill-in for patients. Meanwhile, the impact to daily life is not evaluated in SODAS, and side effects other than weight gain are reduced to one item (tolerability), which may be an oversimplification. In addition, it is an English questionnaire, and the Japanese version is not available yet. We conducted this study to validate a questionnaire for assessing satisfaction with treatment using oral hypoglycemic agents, the Oral Hypoglycemic Agent Questionnaire (OHA-Q), which is written in the Japanese language. We developed a patient-administered questionnaire composed of 20 questions regarding satisfaction, treatment compliance, convenience, effects on daily life and socialization, safety, etc. Then, the reproducibility, factorial structure and validity of the items were examined by analyzing data obtained from patients with type 2 diabetes mellitus receiving oral hypoglycemic agents. Methods Development of OHA-Q To assess treatment satisfaction in patients with type 2 diabetes mellitus receiving oral hypoglycemic agents, we developed the OHA-Q, a questionnaire composed of the following items comprised of 20 questions from 7 domains. Each item is answered by selecting among four ordered categories. The details are shown in Appendix: Oral Hypoglycemic Agent Questionnaire (OHA-Q). Current status of treatment adherence: 1 item (question 1). Operability of treatment: 2 items (questions 2 and 3). Social living: 1 item (question 4). Daily living: 2 item (questions 5, 6 and 7). Appreciation: 4 items: (questions 8, 9 and 10). Somatic symptoms: 8 items (questions 11, 12, 13, 14, 15, 16, 17 and 18). Satisfaction: 2 items (questions 19 and 20). The domains were determined by reference to DTSQ items, i.e., convenience, flexibility, satisfaction, hypoglycemia, etc. The items were drafted and selected based on the clinical experience of an author who interviewed a considerable number of patients treated with OHAs in daily practice. Assessment of reproducibility and validity Subjects The subjects were outpatients with type 2 diabetes mellitus who had been treated with a single oral hypoglycemic agent for the past 1 month or longer. In addition, they had to be at least 20 years old and provide written informed consent. Moreover, the following patients were excluded: patients receiving insulin treatment, patients who had difficulty completing the questionnaires, those with severe complications and other patients judged to be inappropriate by the attending physicians. Contents of the survey The questionnaires used in the survey are as follows: OHA-Q: completed by patients. DTSQ: completed by patients. Physician-filled form: completed by physicians. Survey methods This study was conducted according to the following study procedure. 1. At patient visit The attending physician gave two copies each of the OHA-Q and DTSQ to eligible patients who provided informed consent for participation in this study. The patients filled out their answers on one copy of each questionnaire, without the presence of the attending physician, in a room at the medical institution. Then, the patients enclosed the questionnaires in an envelope, gave them to the attending physician and took the remaining

5 154 H. Ishii, E. Oda copies home. The attending physician filled out the necessary information in the physician-filled forms and mailed them with the questionnaires answered by the patients to the study administrator. 2. Within 1 week from the visit After coming home, the patients answered the OHA-Q and DTSQ within 1 week from their visit and mailed them in the return envelope to the study administrator. 3. Data entry The study administrator entered the data on the received questionnaires and physician-filled forms. 4. Statistical analysis The study administrator sent the entered data to the investigator in charge of statistical analysis. The investigator performed statistical analyses and reported the results to the principal investigator. Implementation structure and study period The implementation structure and study period are as follows: Study institutions: 45 institutions including Seino Internal Medicine Clinic (35 clinics? 10 hospitals). Ethics committee: Ethics Committee, Asano Clinic. Principal investigator: Hitoshi Ishii, Tenri Hospital. Study administrator: ANTERIO Inc. Investigator in charge of statistical analysis: Medical TOUKEI Corp. Study period: August 2010 to December Statistical analysis procedures 1. Patients disposition Of the enrolled patients, the following were excluded from the validity analysis set: those with uncollected or incomplete physician-filled forms and those with an uncollected or incomplete first OHA-Q. Of the validity analysis set, patients with an uncollected or incomplete second OHA-Q were excluded from the reproducibility analysis set. 2. Patients backgrounds In regard to the validity and reproducibility analysis sets, appropriate descriptive statistics were calculated for background factors, such as sex, age, duration of diabetes mellitus and hypoglycemic agents. 3. Validity analysis The following statistical analyses were performed for the validity analysis set. Factor analysis was performed on the OHA-Q item scores to determine subscales. Cronbach s alphas were calculated for each subscale. The correlation coefficients were calculated between the OHA-Q subscale scores and the DTSQ scores. The associations between OHA-Q subscale scores and background factors were examined using the t test, analysis of variance and the Jonckheere Terpstra test. 4. Reproducibility analysis The following statistical analyses were performed for the reproducibility analysis set. Weighted j statistics were calculated for OHA-Q subscale scores. The weights (w) were assigned as follows: Exact agreement: w = 1 1-degree disagreement: w = 2/3 2-degree disagreement: w = 1/3 3-degree disagreement: w = 0 Intraclass correlation coefficients were calculated for OHA-Q subscale scores. Results Patients disposition Patients disposition is shown in Fig. 1. Out of 597 enrolled patients, 114 were excluded mainly because of an incomplete first OHA-Q, and 483 were included in the validity analysis set. Out of 483 patients in the validity analysis set, 64 were excluded mainly because of an incomplete 2nd OHA-Q, and 419 were included in the reproducibility analysis set. Patients backgrounds Patients backgrounds are summarized in Table 1. All background factors had a similar distribution between the validity and reproducibility analysis sets. Summary of OHA-Q item scores The results of OHA-Q item scores are summarized in Table 2. In the validity analysis set (1st OHA-Q), positive answers (score 2 or 3) were observed for many items, and the mean scores were 2.0 or higher for 19 of the 20 items. The mean score was less than 2.0 only for item 14: Are you bothered by the increase in body weight? (mean score

6 Development of a satisfaction questionnaire on oral hypoglycemic agent 155 Fig. 1 Patients disposition Enrolled patients 597 patients Validity analysis set 483 patients Reproducibility analysis set 419 patients Excluded patients from validity analysis 114 patients Uncollected physician-filled form 15 patients Incomplete physician-filled form 26 patients Uncollected 1st OHA-Q 1 patient Incomplete 1st OHA-Q 72 patients Excluded patients from reproducibility analysis 64 patients Uncollected 2nd OHA-Q 19 patients Incomplete 2nd OHA-Q 45 patients of 1.7). Similar results were obtained from the reproducibility analysis set (1st and 2nd OHA-Q). Reproducibility of the OHA-Q item scores Table 3 shows the results of reproducibility analysis of OHA-Q item scores in the reproducibility analysis set. Weighted j statistics were 0.6 or higher for 17 of the 20 items. The statistics were less than 0.6 for the following three items: item 2: difficulty swallowing (j = 0.558); item 8: the number of doses (j = 0.590); and item 18: hypoglycemia (j = 0.578). All items showed a degree of reproducibility without practical issues. Factor analysis of OHA-Q item scores Table 4 shows factor analysis results for OHA-Q item scores in the validity analysis set. A three-factor model with varimax rotation was applied to the scores of all 20 items. When the items with a factor loading of 0.4 or higher were considered, a simple structure with all items loading on one factor was obtained. Based on the above results and item contents, subscale scores were constructed as follows: Treatment convenience score: sum of scores for items 1 9. Somatic symptom score: sum of scores for items Satisfaction score: sum of scores for items 10, 19 and 20. Cronbach s alphas for the subscales were 0.902, and 0.743, which indicate internal consistency of the subscales. Reproducibility of OHA-Q subscale scores Figure 2 is a scatter plot of OHA-Q subscale scores (1st OHA-Q vs. 2nd OHA-Q) and the estimated results of intraclass correlation coefficients for the reproducibility analysis set. Intraclass correlation coefficients were 0.7 or higher for all scores, showing high reproducibility. Correlation between OHA-Q subscale scores and DTSQ scores Table 5 shows the calculated univariate summary statistics and correlation coefficients between OHA-Q subscale scores and DTSQ scores for the validity analysis set. The correlations between OHA-Q subscale scores (Pearson correlation coefficients) showed positive values of 0.4 or higher for every combination. The highest coefficient was 0.59 for treatment convenience/satisfaction, followed by somatic symptom/satisfaction (0.47) and treatment convenience/somatic symptom (0.43). The correlation between the OHA-Q subscale scores and DTSQ satisfaction scores also showed positive values for all combinations. The highest correlation coefficient was 0.57 for OHA-Q satisfaction/dtsq satisfaction, followed by OHA-Q treatment convenience/dtsq satisfaction (0.43) and OHA-Q somatic symptom/dtsq satisfaction (0.29). There were no strong correlations between OHA-Q subscale scores and DTSQ hyperglycemia/hypoglycemia scores. Association between OHA-Q subscale scores and patient backgrounds Table 6 shows the examination results for the association between OHA-Q subscale scores and patient backgrounds for the validity analysis set. Significantly higher treatment convenience scores were observed in patients age 65 years or older, patients with HbA1c of less than 6.5 %, and patients with a treatment compliance rate of 80 % or higher. Moreover, there were significant differences among hypoglycemic agents (P = 0.013). Relatively high scores were obtained for SU (mean score of 21.3), thiazolidine derivatives (21.8)

7 156 H. Ishii, E. Oda Table 1 Patients backgrounds Items Statistics/ category Validity analysis set Reproducibility analysis set Number of patients 483 (100.0 %) 419 (100.0 %) Age Mean (SD), N 64.0 (11.7), (11.6), 419 Sex Male 294 (60.9 %) 257 (61.3 %) Female 189 (39.1 %) 162 (38.7 %) Duration of diabetes mellitus (year) Mean (SD), N 6.5 (5.9), (5.9), 414 Body mass index Mean (SD), N 24.3 (4.0), (3.9), 412 Diastolic blood pressure (mmhg) Mean (SD), N 74.3 (10.7), (10.7), 413 Systolic blood pressure (mmhg) Mean (SD), N (14.7), (14.7), 413 HbA1c (%) Mean (SD), N 6.5 (0.8), (0.8), 414 Hypoglycemic agents SU 98 (20.3 %) 85 (20.3 %) Biguanide 110 (22.8 %) 94 (22.4 %) a-glucosidase 91 (18.8 %) 76 (18.1 %) inhibitor Thiazolidine 97 (20.1 %) 86 (20.5 %) derivative DPP-4 inhibitor 87 (18.0 %) 78 (18.6 %) Years elapsed since prescription Mean (SD), N 2.0 (2.1), (2.1), 419 History of hypoglycemia: mild Presence 5 (1.0 %) 5 (1.2 %) Absence 478 (99.0 %) 414 (98.8 %) History of hypoglycemia: serious Presence 6 (1.2 %) 3 (0.7 %) Absence 475 (98.3 %) 415 (99.0 %) Unknown 2 (0.4 %) 1 (0.2 %) Status of treatment compliance % or higher 419 (86.7 %) 365 (87.1 %) \80 % 22 (4.6 %) 19 (4.5 %) 3. \50 % 1 (0.2 %) 0 (0.0 %) Unknown 41 (8.5 %) 35 (8.4 %) Antihypertensive agents Presence 245 (50.7 %) 210 (50.1 %) Absence 237 (49.1 %) 208 (49.6 %) Unknown 1 (0.2 %) 1 (0.2 %) Lipid-lowering agents Presence 236 (48.9 %) 207 (49.4 %) Absence 245 (50.7 %) 210 (50.1 %) Unknown 2 (0.4 %) 2 (0.5 %) Number of agents used in addition to a 0 73 (15.1 %) 64 (15.3 %) hypoglycemic agent (22.4 %) 98 (23.4 %) 2 83 (17.2 %) 76 (18.1 %) 3 or more 217 (44.9 %) 179 (42.7 %) Unknown 2 (0.4 %) 2 (0.5 %) 1st DTSQ Hyperglycemia (0, none to 6, almost always) Mean (SD), N 2.3 (1.8), (1.8), 417 Hypoglycemia (0, none to 6, almost always) Mean (SD), N 1.3 (1.7), (1.7), 418 Satisfaction (0, lowest to 36, highest) Mean (SD), N 28.1 (5.5), (5.4), 414 and the DPP-4 inhibitor (21.9), whereas low scores were obtained for biguanides (19.9) and a-glucosidase inhibitors (20.4). Significantly higher somatic symptom scores were observed in male patients and patients without use of antihypertensive agents. Moreover, the scores tended to decrease as the number of agents used in addition to a hypoglycemic agent increased (P = 0.015). Significantly higher satisfaction scores were observed in patients age 65 years or older, patients with HbA1c of less than 6.5 %, and patients with a treatment compliance rate of 80 % or higher.

8 Development of a satisfaction questionnaire on oral hypoglycemic agent 157 Table 2 Summary of OHA-Q item scores Items Discussion Mean (SD) of item scores Validity analysis set Reproducibility analysis set 1st 1st 2nd Number of patients Missed dose 2.2 (0.8) 2.2 (0.8) 2.1 (0.7) 2. Difficulty swallowing 2.6 (0.6) 2.6 (0.6) 2.5 (0.6) 3. Carrying and preparing 2.4 (0.7) 2.4 (0.7) 2.3 (0.7) for taking the agent 4. People around the patient 2.5 (0.7) 2.4 (0.7) 2.4 (0.7) 5. Following the meal schedule 2.2 (0.8) 2.2 (0.8) 2.1 (0.8) 6. Interval between taking the 2.2 (0.8) 2.2 (0.8) 2.1 (0.8) agent and a meal 7. Compliance with treatment 2.2 (0.8) 2.2 (0.8) 2.1 (0.8) schedule 8. Number of doses 2.4 (0.7) 2.4 (0.7) 2.3 (0.7) 9. Taking the agent at a place 2.3 (0.7) 2.3 (0.7) 2.2 (0.8) other than home 10. Desire to continue the 2.1 (0.8) 2.1 (0.8) 2.0 (0.9) treatment 11. Rumbling stomach 2.1 (0.9) 2.1 (0.8) 2.0 (0.8) 12. Diarrhea 2.2 (0.8) 2.2 (0.8) 2.2 (0.8) 13. Constipation 2.0 (0.9) 2.0 (0.9) 2.0 (0.9) 14. Increased body weight 1.7 (1.0) 1.8 (0.9) 1.8 (0.9) 15. Tendency to become hungry 2.1 (0.8) 2.1 (0.8) 2.1 (0.8) easily 16. Nausea 2.2 (0.8) 2.2 (0.8) 2.2 (0.8) 17. Bodily swelling 2.3 (0.8) 2.3 (0.8) 2.2 (0.8) 18. Hypoglycemia 2.2 (0.8) 2.3 (0.8) 2.2 (0.8) 19. Glycemic control 2.2 (0.7) 2.2 (0.7) 2.1 (0.6) 20. Satisfaction with the current agent 2.3 (0.6) 2.3 (0.6) 2.2 (0.6) 3, Best score; 0, worst score We developed the OHA-Q, a rating scale designed to assess satisfaction with treatment with oral hypoglycemic agents, which is a patient-administered questionnaire composed of 20 questions regarding satisfaction, treatment compliance, convenience, effects on daily living and socialization, safety, etc. We analyzed the data obtained from patients with type 2 diabetes mellitus treated with an oral hypoglycemic agent (483 patients in the validity analysis set and 419 in the reproducibility analysis set) to examine the reproducibility, factorial structure and validity of the question items. Weighted j statistics were calculated as an index of reproducibility for the OHA-Q item scores, all 20 items, and the result showed high reproducibility enough for practical use. Intraclass correlation coefficients were Table 3 Reproducibility of OHA-Q item scores [reproducibility analysis set] Items Weighted j statistics Point estimate 95 % confidence interval 1. Missed dose (0.639, 0.755) 2. Difficulty swallowing (0.483, 0.633) 3. Carrying and preparing for taking the (0.567, 0.698) agent 4. People around the patient (0.561, 0.689) 5. Following the meal schedule (0.587, 0.711) 6. Interval between taking the agent (0.623, 0.740) and a meal 7. Compliance with treatment schedule (0.606, 0.732) 8. Number of doses (0.522, 0.658) 9. Taking the agent at a place other than (0.592, 0.720) home 10. Desire to continue the treatment (0.612, 0.729) 11. Rumbling stomach (0.632, 0.748) 12. Diarrhea (0.639, 0.757) 13. Constipation (0.695, 0.798) 14. Increased body weight (0.591, 0.705) 15. Tendency to become hungry easily (0.593, 0.720) 16. Nausea (0.576, 0.706) 17. Bodily swelling (0.614, 0.737) 18. Hypoglycemia (0.514, 0.643) 19. Glycemic control (0.586, 0.725) 20. Satisfaction with the current agent (0.546, 0.685) calculated as an index of reproducibility for the three subscale scores calculated as sums of several item scores, and all coefficients were 0.7 or higher, showing high reproducibility. Based on the results of factor analysis of the OHA-Q item scores, a simple structure was obtained, and three OHA-Q subscale scores were constructed. Treatment convenience score: sum of scores for items 1 9. Somatic symptom score: sum of scores for items Satisfaction score: sum of scores for items 10, 19 and 20. The treatment convenience subscale consists of the following items in the original domain: current status of treatment compliance (question 1), operability of treatment (questions 2 and 3), socialization (question 4), daily living (question 5 and 6) and appreciation (questions 7, 8 and 9). Similarly, the somatic symptom subscale consists of somatic symptoms (questions 11, 12, 13, 14, 15, 16, 17 and 18), and the satisfaction subscale consists of appreciation (question 10) and satisfaction (questions 19 and 20). While three of the four items in the original domain of

9 158 H. Ishii, E. Oda Table 4 Factor analysis of OHA-Q item scores [validity analysis set] Items Factor loading (3-factor varimax rotation) Communality N = 483 a Factor loading is more than Missed dose a Difficulty swallowing a Carrying and preparing for taking the agent a People around the patient a Following the meal schedule a Interval between taking the agent and a meal a Compliance with treatment schedule a Number of doses a Taking the agent at a place other than home a Desire to continue the treatment a Rumbling stomach a Diarrhea a Constipation a Increase in body weight a Tendency to become hungry easily a Nausea a Bodily swelling a Hypoglycemia a Glycemic control a Satisfaction with the current agent a Variance of the factors Cronbach s alpha nd Treatment convenience score st 2nd Somatic symptom score st 2nd Satisfaction score st Summary statistics 1st 2nd Summary statistics 1st 2nd Summary statistics 1st 2nd N N N Mean Mean Mean SD SD SD Median Median Median 6 6 Minimum 2 3 Minimum 2 4 Minimum 0 0 Maximum Maximum Maximum 9 9 Intraclass correlation coefficient Intraclass correlation coefficient Intraclass correlation coefficient Point estimate Point estimate Point estimate % C.I. ( 0.747, 0.820) 95% C.I. ( 0.763, 0.832) 95% C.I. ( 0.692, 0.780) Fig. 2 Reproducibility of OHA-Q subscale scores (reproducibility analysis set)

10 Development of a satisfaction questionnaire on oral hypoglycemic agent 159 Table 5 Correlation between OHA-Q subscale scores and DTSQ scores (validity analysis set) Statistics OHA-Q DTSQ Treatment convenience Somatic symptom Satisfaction Hyperglycemia Hypoglycemia Satisfaction Univariate summary statistics Mean Standard deviation Median Minimum Maximum N Assessment scale Score OHA-Q DTSQ Treatment convenience Somatic symptom Satisfaction Hyperglycemia Hypoglycemia Satisfaction Correlation coefficient matrix OHA-Q Treatment convenience Somatic symptom Satisfaction DTSQ Hyperglycemia Hypoglycemia Satisfaction Upper right Pearson s correlation coefficient Lower left Spearman s correlation coefficient appreciation were included in the treatment convenience subscale, only question 10 ( Do you want to continue taking your current hypoglycemic agent? ) was classified in the satisfaction subscale. Based on the examination of the content of the item (Q10) and other items in the subscales of treatment convenience and satisfaction, we adapted the results of the factor analysis rather than the original domain. There was a positive correlation between OHA-Q subscale scores. There was also a positive correlation between OHA-Q subscale scores and DTSQ satisfaction scores. These correlations are expected results and show the validity of OHA-Q. OHA-Q treatment convenience scores and OHA-Q satisfaction scores were high in patients with characteristics, such as high age (65 years or older), low HbA1c and good treatment compliance. Elderly patients may have relatively few time constraints caused by work, etc. Consequently, treatment convenience is assumed to have been evaluated as high. It is not surprising that good treatment compliance was observed in patients who evaluated treatment convenience as high. Good treatment compliance may result in HbA1c levels tending to be low. The SOADAS score had a similar association with HbA1c, that is, patients with lower HbA1c were apt to have higher SODAS scores [13]. OHA-Q treatment convenience scores were higher in patients receiving SU, thiazolidine derivatives and the DPP-4 inhibitor than in those receiving biguanides and a-glucosidase inhibitors. Although biguanides and a-glucosidase inhibitors usually need to be administered three times a day, the other three agents are administered twice a day or less often. The difference in the number of doses may have affected the appreciation of treatment convenience by patients. OHA-Q somatic symptom scores were high in patients with characteristics such as male sex, no use of antihypertensive agents and the small number of agents used in addition to a hypoglycemic agent. There are several reports on a tendency for male patients to show higher satisfaction with treatment for diabetes mellitus [14 16], showing consistency with the results of our study. Moreover, in patients receiving antihypertensive agents, symptoms attributable to hypertension or adverse reactions to the agents may affect somatic symptom scores. In this study, subjects were restricted to patients treated with a single OHA. The restriction of patients was expected to make comparison among OHAs easy to interpret, which was the intention at study design. However, the comparison is not straightforward, because the background factors of patients are quite different among OHA groups. Further analyses with multivariate methods to adjust the difference of background would be necessary to reach some

11 160 H. Ishii, E. Oda Table 6 Association between OHA-Q subscale scores and patient backgrounds [validity analysis set] Items Category N OHA-Q subscale score Treatment convenience Somatic symptom Satisfaction Mean (SD) Mean (SD) Mean (SD) Validity analysis set (4.9) 16.8 (4.6) 6.5 (1.7) Age \ (5.0) 16.6 (4.4) 6.1 (1.7) 65 or oder (4.7) 16.9 (4.7) 6.9 (1.6) t test P \ 0.001*** P = P \ 0.001*** Sex Male (4.8) 17.2 (4.7) 6.6 (1.7) Female (5.1) 16.2 (4.4) 6.4 (1.8) t test P = P = 0.024* P = Duration of diabetes mellitus \5 years (4.8) 17.2 (4.6) 6.6 (1.8) 5 years or longer (5.0) 16.5 (4.6) 6.5 (1.7) t test P = P = P = Body mass index \ (4.9) 16.9 (4.6) 6.6 (1.7) 25 or higher (5.0) 16.7 (4.6) 6.5 (1.8) t test P = P = P = Diastolic blood pressure \90 mmhg (4.9) 16.7 (4.6) 6.5 (1.7) 90 mmhg or more (5.4) 17.9 (4.7) 6.7 (1.7) t test P = P = P = Systolic blood pressure \130 mmhg (4.9) 16.7 (4.5) 6.5 (1.6) 130 mmhg or more (5.0) 17.0 (4.7) 6.6 (1.8) t test P = P = P = HbA1c \6.5 % (4.4) 16.9 (4.5) 6.7 (1.6) 6.5 % or more (5.3) 16.7 (4.6) 6.3 (1.8) t test P = 0.006** P = P = 0.024* Hypoglycemic agents SU (5.1) 16.7 (5.2) 6.7 (1.6) Biguanide (4.5) 16.3 (4.3) 6.3 (1.6) a-glucosidase inhibitor (4.7) 17.1 (3.9) 6.5 (1.7) Thiazolidine derivative (4.9) 16.4 (4.8) 6.5 (1.9) DPP-4 inhibitor (5.1) 17.8 (4.4) 6.8 (1.7) ANOVA P = 0.013* P = P = Elapsed years \1 year (5.0) 17.0 (4.7) 6.6 (1.8) Since prescription 1 year or longer (4.8) 16.6 (4.4) 6.5 (1.6) t test P = P = P = History of hypoglycemia: Presence (4.3) 17.6 (7.8) 7.2 (1.6) Mild Absence (4.9) 16.8 (4.5) 6.5 (1.7) t test P = P = P = History of hypoglycemia: Presence (5.4) 15.2 (4.6) 6.7 (1.2) Serious Absence (4.9) 16.8 (4.6) 6.5 (1.7) t test P = P = P = Status of treatment compliance \80 % (7.0) 15.2 (4.1) 5.9 (2.2) 80 % or higher (4.6) 16.9 (4.6) 6.7 (1.6) t test P \ 0.001*** P = P = 0.035* Antihypertensive agents Presence (4.6) 16.3 (4.4) 6.5 (1.6) Absence (5.2) 17.3 (4.7) 6.5 (1.8) t test P = P = 0.021* P = Lipid-lowering agents Presence (4.8) 16.8 (4.6) 6.5 (1.7) Absence (5.0) 16.8 (4.6) 6.5 (1.7) t test P = P = P = Number of agents used in addition to a hypoglycemic agent *P \ 0.050, **P \ 0.010, ***P \ (4.3) 17.8 (4.2) 6.7 (1.7) (5.5) 17.1 (4.9) 6.4 (1.9) (4.9) 16.5 (4.2) 6.4 (1.7) 3 or more (4.7) 16.5 (4.6) 6.6 (1.6) JT test P = P = 0.015* P = 0.979

12 Development of a satisfaction questionnaire on oral hypoglycemic agent 161 conclusions about comparison of OHAs, which should be reported in another article. Characteristics of OHAs, such as, specific symptoms, might become apparent. Patients treated with a single OHA may have milder conditions than patients treated with multiple OHAs who are included in the target population of OHA-Q. Properties of OHA-Q in patients with combination therapy should be investigated in the future. Another limitation of this study is that a substantial number of patients were excluded from statistical analyses. The major reason for exclusion was that the patients had filled out an incomplete OHA-Q form. This suggests that receiving incomplete OHA-Qs might happen frequently in daily practice. OHA-Q has 20 items, which are useful to evaluate treatment satisfaction comprehensively, but may be too long to complete for some patients. Taking this into consideration, it might be worthwhile to develop a short version of OHA-Q with ten items or fewer, like in the SOADAS. The OHA-Q is written in Japanese, and the English version should be validated in a separate study. Based on the above results and the considerations discussed, the OHA-Q may have adequate reproducibility and validity as an assessment scale for satisfaction with treatment using oral hypoglycemic agents in patients with type 2 diabetes mellitus. Appendix: Oral Hypoglycemic Agent Questionnaire (OHA-Q) Entry date: (day) (month) Registration number Questionnaire on oral antidiabetic drugs For each question, please circle the response that best reflects how you feel. 1. Do you ever forget to take your diabetes medication? (How many times a week?) 1. Never 2. Almost never 3. Once or twice a week 4. At least three times a week 2. Are you concerned about the size of the tablets, difficulty swallowing the tablets, etc., when taking diabetes medication? 3. Is handling/carrying/preparing to taking diabetes medication troublesome? 1. Not troublesome at all 2. Hardly troublesome 3. Sometimes troublesome 4. Very troublesome 4. Are you concerned about being seen by others when taking diabetes medication outside of your home? 5. Is it a burden to eat meals at regular times in order to take diabetes medication? 1. Not a burden at all 2. Almost no burden 3. Sometimes a burden 4. Very much of a burden 6. Is being punctual in taking your diabetes medication and your meals troublesome? 1. Not troublesome at all 2. Hardly troublesome 3. Sometimes troublesome 4. Very troublesome 7. Is it a burden to take diabetes medication at predetermined times? 1. Not a burden at all 2. Almost no burden 3. Sometimes a burden 4. Very much of a burden 8. Is the dosing frequency for diabetes medication a hassle? 1. Not a hassle at all 2. Almost no hassle 3. Sometimes a hassle 4. Very much of a hassle 9. Is it difficult to take diabetes medication outside of your home? 1. Not difficult at all 2. Hardly difficult 3. Sometimes difficult 4. Very difficult 10. Do you want to continue to take your current diabetes medication? 1. Yes, definitely 2. Yes 3. Not very much 4. No, I would like to stop

13 162 H. Ishii, E. Oda 11. Are you concerned about passing gas or rumbling in your stomach? 12. Are you concerned about diarrhea? 13. Are you concerned about constipation? 14. Are you concerned about weight gain? 15. Are you concerned about readily becoming hungry? 16. Are you concerned about having an upset stomach? 17. Are you concerned about swelling of your body? 18. Are you worried about hypoglycemia? 1. Not worried at all 2. Hardly worried 3. Sometimes worried 4. Very worried 19. Are you satisfied with your current blood glucose control? 1. Very satisfied 2. Generally satisfied 3. Not very satisfied 4. Dissatisfied 20. Are you satisfied with your current treatment with the diabetes medication? 1. Very satisfied 2. Generally satisfied 3. Not very satisfied 4. Dissatisfied References 1. Patrick DL, Burke LB, Powers JH, et al. Patient-reported outcomes to support medical product labeling claims: FDA perspective. Value Health. 2007;10(Suppl 2):S Payne R, Mathias SD, Pasta DJ, et al. Quality of life and cancer: satisfaction and side effects with transdermal fentanyl versus oral morphine. J Clin Oncol. 1998;16(4): Chatterton ML, Scott-Lennox J, Wu AW, et al. Quality of life and treatment satisfaction after the addition of lamivudine or lamivudine plus loviride to zidovudine-containing regimens in treatmentexperienced patients with HIV infection. Pharmacoeconomics. 1999;15(Suppl 1): Mathias SD, Warren EH, Colwell HH, et al. A new treatment satisfaction measure for asthmatics: a validation study. Qual Life Res. 2000;9(7): Atkinson MJ, Shinha A, Hass SL, et al. Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes. 2004;2: The DCCT research group. Reliability and validity of a diabetes quality-of-life measure for the diabetes control and complications trial (DCCT). Diabetes Care. 1988;11(9): Bradley C. Diabetes treatment satisfaction questionnaire (DTSQ). In: Bradley C, editor. Handbook of psychology and diabetes. Chur: Harwood Academic Publ.; Ishii H, Bradley C, Riazi A, Barendse S, Yamamoto T. The Japanese Version of the Diabetes Treatment Satisfaction Questionnaire (DTSQ): translation and clinical evaluation. J Clin Exp Med. 2000;192: Polonsky WH, et al. Assessment of diabetes-related distress. Diabetes Care. 1995;18(6): Ishii H, Yamamoto T, Ohashi Y. Development of insulin therapy related quality of life measure (ITR-QOL). J Japan Diabetes Soc. 2001;44: Ishii H, Anderson JH Jr, Yamamura A, et al. Improvement of glycemic control and quality-of-life by insulin lispro therapy: assessing benefits by ITR-QOL questionnaires. Diabetes Res Clin Pract. 2008;81(2):

14 Development of a satisfaction questionnaire on oral hypoglycemic agent Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs. 2005;65(3): Donatti C, Wild D, Horblyuk R, et al. Psychometric evaluation of the Satisfaction with Oral Anti-Diabetic Agent Scale (SOADAS). Diabetes Res Clin Pract. 2008;80(1): Rubin RR, Peyrot M. Quality of life and diabetes. Diabetes Metab Res Rev. 1999;15: Sampson MJ, Singh H, Dhatariya KK, et al. Psychometric validation and use of a novel diabetes in-patient treatment satisfaction questionnaire. Diabet Med. 2009;26(7): Biderman A, Noff E, Harris SB, et al. Treatment satisfaction of diabetic patients: what are the contributing factors? Fam Pract. 2009;26(2):102 8.