| Methods |
A 2 by 2 factorial design with patients randomly allocated to warfarin (long half‐life) or acenocoumarol (short‐half life) and to either intensive education or standard education. Allocation concealment was achieved by central computerized randomization balanced in blocks of 2, 4, and 6 patients |
| Participants |
Patients over 18 years old were enrolled if they needed at least 3‐month oral anticoagulant therapy (OAT) following IV infusion for a thromboembolic disease. Patients were excluded if they were pregnant, had any contra‐indication to anticoagulant therapy, recent surgery (< 4 days) or progressive bleeding |
| Interventions |
Patients assigned to warfarin received a dose of 6 mg (up to 70 years old) or 4 mg (over 70 years) those assigned to acenocoumarol received a dose of 4 mg (up to 70 years old) or 3 mg (over 70 years). Subsequent doses were adjusted to maintain the international normalized ratio (INR) within the target range of 2 to 3. Patients took a single dose of the oral anticoagulant (OA) daily at 8pm. The standard education group received the minimum information consistent with ethical OAT with no particular emphasis on the necessity of strict compliance. Patients in the intensive education group received information about the causes of anticoagulation instability and the importance of strict adherence. The intensive education group were provided information through visual material, were visited daily by nurses and physicians to repeat some items, and were tested daily about their education. The education, either standard or intensive was given until hospital discharge |
| Outcomes |
The number of tablets left in the bottle were recorded at follow‐up at 1, 2, and 3 months
Measurement of clinical health outcomes: laboratory INR measurements were made in the morning and recorded in the patient's diary. The raw INR levels, the % of INRs in target range, the % of time in target range and %age of dose adjustments were recorded. Follow‐up visits were scheduled at 1, 2, and 3 months. During each visit patients were asked about their symptoms or bleeding events |
| Notes |
The follow‐up period was only 3 months but since the results proved to be negative it still meets the criteria for inclusion in the review |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Computer‐generated. Centralized in the Clinical Pharmacology Unit. A telephone call was needed to randomize the patients |
| Allocation concealment (selection bias) |
Low risk |
Allocation concealment described and appropriate. (pg 460) "Concealment of allocation was received by central computerised randomisation. balanced in groups of 2, 4 or 6 patients." |
| Selective reporting (reporting bias) |
Low risk |
Author's note: the primary outcome was not a clinical endpoint, but the stability of INR. All endpoints are reported in the paper |
| Other bias |
Low risk |
No other risks of bias noted in discussion; no other clear risks of bias in article |
| Blinding of outcome assessment (detection bias)
Adherence measure |
Low risk |
(PRIMARY) MEMS ‐ Although study personnel were not blinded (pg 459), this is not likely to affect this outcome measure |
| Blinding of outcome assessment (detection bias)
Patient outcome |
Low risk |
(PRIMARY) INR VALUES ‐ Author note: the primary endpoint was the stability of INR. INR levels were blindly assessed |
| Blinding of participants (performance bias)
Adherence measure |
High risk |
(PRIMARY) MEMS ‐ (pg 459) A 2 by 2 open randomized factorial design was used. Patients were not told of the purpose of the pill cap but it is likely they inferred the purpose of the cap. (pg 459) "The patients were not informed about the full purpose of the pill bottle;only told that it recorded the number of openings." |
| Blinding of participants (performance bias)
Patient outcome |
Low risk |
(PRIMARY) INR VALUES ‐ Unclear if patients were blinded but IVT values are determined by a blood test and difficult for patients to impact the outcome |
| Blinding of personnel (performance bias)
Adherence measure |
Low risk |
(PRIMARY) MEMS ‐ Although study personnel were not blinded (pg 459), this is not likely to affect this outcome measure |
| Blinding of personnel (performance bias)
Patient outcome |
Low risk |
(PRIMARY) INR VALUES ‐ Author's note: the primary endpoint was the stability of INR. INR levels were blindly assessed |
| Incomplete outcome data (attrition bias)
Adherence measure |
Low risk |
(PRIMARY) MEMS ‐ Follow‐up is balanced across groups. Reasons for loss to follow‐up provided and unlikely to affect study outcomes |
| Incomplete outcome data (attrition bias)
Patient outcome |
Low risk |
(PRIMARY) INR VALUES ‐ Follow‐up is balanced across groups. Reasons for loss to follow‐up provided and unlikely to affect study outcomes |
