Aisen 2003a.
| Methods | Double blind randomised controlled trial, 12 months | |
| Participants | 351 participants (240 intervention, 111 control) who had MMSE 13‐26, aged > 50 years, were out‐patient in USA | |
| Interventions | Intervention 1: Naproxen sodium 220 mg oral twice (118 participants) Intervention 2: Rofecoxib 25 mg oral once (122 participants) Control: Placebo |
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| Outcomes | Cognition (ADAScog 0‐70 lower score = improvement) at 6, 12 months (CDR‐sob lower score = improvement) at 6, 12 months (NPI 0‐144 lower score = improvement) at 6, 12 months Activity of daily living (ADCS‐ADL 0‐78 higher score = improvement) at 6, 12 months Qulity of life (QoL‐AD higher score = improvement) at 6, 12 months |
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| Notes | source of funding: a grant from the national institute on aging and the general clinical research centre program of the national centre for research resources | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk |
Quote: The randomisation process used a permuted block design with block size of 3 stratified by site. The randomisation sequence was generated by the ADCS data centre Comment: done |
| Allocation concealment (selection bias) | Low risk |
Quote 1: Scratch‐off code‐breakers were used so that instances of unbinding would be documented. All code breakers were collected at the end of the trial. Comment: Probably done |
| Blinding (performance bias and detection bias) All outcomes | Low risk |
Quote 1: Rofecoxib tablets were over‐encapsulated to allow preparation of an identical placebo capsule. Naproxen sodium tablets and identical placebo tables were supplied by?.. Quote 2: Adequacy of masking was assessed by questionnaires completed by participants, caregivers, psychometrists, and site investigators. The results of questionnaires at 12 months indicated that the percentage of participants and informants who believed they were taking active study medication and active study medication also did not differ significantly across the treatment group, indicating that blinding was adequately maintained. Quote3: the randomisation code was broken in 1 instance, based on clinical need for the management of an acute medical problem Comment: acceptable |
| Incomplete outcome data (attrition bias) All outcomes | Low risk |
Quote 1: Reason for loss follow up are caregiver issue and adverse event Comment: Reasons for missing outcome data unlikely to be related to true outcome Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across group |
| Selective reporting (reporting bias) | Low risk | All primary outcomes were reported, but not all secondary outcome such as institutionalisation Comment: The study protocol is not available, but all of the study’s pre‐specified outcomes have been reported in the pre‐specified way in methodology |
| Other bias | Low risk |
Comment: The study appears to be free of other sources of bias |