Matsumura 2012.
| Methods | Randomized controlled trial | |
| Participants | The study location was 29 hospitals or clinics in Japan 103 participants were randomized to the intervention group and 104 participants were randomized to the control group The inclusion criteria were 20 years or older, hypertension, who could be treated with angiotensin II receptor blockers (ARBs) and diuretics (thiazides or related sulphonamide compounds) The exclusion criteria were extremely high blood pressure (= 200 mm Hg in systolic or = 120 mm Hg in diastolic blood pressure), or a serious renal or liver dysfunction, taking more than 4 tablets excluding the study drugs |
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| Interventions | Intervention: COMBINATION PILL
The intervention was a combination pill instead of multiple pills. Patients assigned to the intervention group received a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg). Follow‐up was done at 1, 3, and 6 months Control: MULTIPLE PILLS Control patients were provided with an angiotensin receptor blocker and a diuretic. Follow‐up was done at 1, 3, and 6 months. Adherence outcomes and blood pressure were measured at the 1, 3, and 6‐month appointments; patient outcomes at before and 6 months after randomization |
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| Outcomes | The measures of adherence were pill counts performed at 1, 3, and 6 months. Adherence rates were calculated for each visit using the following formula: adherence rate (%) = [(number of prescribed pills – number of residual pills)/number of prescribed pills] × 100. Non‐adherence was defined as an adherence rate of less than 90% The patient outcomes were blood pressure, adverse events, and blood variables. After resting for at least 5 minutes, blood pressures were measured twice in a sitting position using a standard sphygmomanometer. The mean of 2 measurements was used in the present analysis. Blood variables including hematocrit, serum creatinine, serum sodium, serum potassium and serum uric acid were measured before and 6 months after randomization. Secondary outcomes were achieved follow‐up blood pressure, adverse events, and blood variables |
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| Notes | ― | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computerized randomization was used. (pg 1416) "Study treatments were allocated using a central, computer‐based, randomization service accessible by the internet and telephone" |
| Allocation concealment (selection bias) | Low risk | Central randomization was used. "Study treatments were allocated using a central, computer‐based, randomization service accessible by the internet and telephone" (pg 1416) |
| Selective reporting (reporting bias) | Unclear risk | No protocol available; although it appears that everything was reported it is difficult to determine this without a protocol |
| Other bias | High risk | The authors note that "...the present study was limited by the facts that there were not enough subjects and that the study period might not be sufficiently long enough to detect the small difference in adherence rates between the combination pill and control groups. In the present study, the patients were treated over 6 months. If the treatment period is to be longer, medication adherence might be improved in the combination pill group compared with the control group. Moreover, the present study provides little information regarding medication persistence. In order to achieve optimal outcomes in the treatment of hypertension, patients were required to take their medications not only properly (medication adherence) but also to continue to do so throughout long‐term treatment (persistence)." adherence rate is the selection bias of the patients participating in the present study, because all patients were screened for run‐in phases 1 and 2. The patients with a low adherence rate might be excluded during run‐in periods. Therefore, this excellent medication adherence rate observed in the present study might not be applicable to general Japanese hypertensive patients. In addition, many participants were not newly diagnosed hypertensive patients, but rather had been treated with antihypertensive drugs for several years.25 Furthermore, a recent study demonstrated that merely participating in a clinical trial significantly increases adherence.26 Even considering these limitations, however, the findings of the present study are largely new and provide important information on medication adherence regarding a combination pill of antihypertensive drugs" ‐ p.1420‐1421 "Electronic monitoring seems to be the most accurate method to evaluate medication adherence. 27 Unfortunately, however, the cost of this device precluded its use in the present study. Accordingly, the indirect method of pill counts was applied in the present study. This method can be applied to estimate the quantities of medications a patient presumably takes". (pg 1421) |
| Blinding of outcome assessment (detection bias) Adherence measure | Unclear risk | (PRIMARY) PILL COUNT ‐ No information on whether pill count was computerized. There is insufficient information to permit judgment of 'Low risk' or 'High risk' |
| Blinding of outcome assessment (detection bias) Patient outcome | Unclear risk | (PRIMARY) BLOOD PRESSURE ‐ No information on whether the method of taking blood pressure was computerized. There is insufficient information to permit judgment of 'Low risk' or 'High risk'. Open trial |
| Blinding of participants (performance bias) Adherence measure | High risk | (PRIMARY) PILL COUNT ‐ Open trial. Patients aware of allocation due to the nature of the intervention |
| Blinding of participants (performance bias) Patient outcome | Low risk | (PRIMARY) BLOOD PRESSURE ‐ This is an objective measure of outcome. Lack of blinding of patients is not likely to affect the end results |
| Blinding of personnel (performance bias) Adherence measure | Unclear risk | (PRIMARY) PILL COUNT ‐ No information on blinding given. There is insufficient information to permit judgment of 'Low risk' or 'High risk' |
| Blinding of personnel (performance bias) Patient outcome | Unclear risk | (PRIMARY) BLOOD PRESSURE ‐ No information on blinding given. There is insufficient information to permit judgment of 'Low risk' or 'High risk' |
| Incomplete outcome data (attrition bias) Adherence measure | Low risk | (PRIMARY) PILL COUNT ‐ All patients were included in ITT analysis irrespective of completion. Overall, there was a high rate of completion |
| Incomplete outcome data (attrition bias) Patient outcome | Low risk | (PRIMARY) BLOOD PRESSURE ‐ All patients were included in ITT analysis irrespective of completion. Overall, there was a high rate of completion |