|Methods||Multi-centre cluster-randomised controlled trial involving 50 (computerised) primary care centres across the West Midlands, UK, over a 12 month period. Randomisation was stratified by levels of deprivation (Townsend quartiles) and practice size. A subsidiary trial was embedded in the intervention arm, comparing two different screening strategies. Overall time period was from October 2001 to February 2003.|
|Participants||Male and female patients over 65 years of age attending general practices in the UK. |
Age range was 65 - 98 years, average age of 73.5 years.
A random sample of 10,000 patients from the intervention group were allocated randomly to either systematic or opportunistic screening. Randomisation was stratified according to whether or not AF had been previously diagnosed in order to have an equal prevalence of known AF on both arms.
A random sample of 5000 was selected from the control population. After sampling, lists were returned to practices to remove those who had died, moved or were terminally ill. These were replaced from a back-up list which had been randomised at the same time as the initial list.
Final number of participants in control arm = 4963 from 25 general practices.
Final number of participants in intervention arms = 4933 for opportunistic screening and 4933 for systematic screening from 25 general practices.
Baseline AF prevalence in the control population higher than in the intervention populations (7.9% versus 6.9%)
Staff at primary care centres in the intervention arms were given training on the importance of AF detection, available treatment options, and were encouraged to consider opportunistic screening of patients. Staff at control centres were given no training. Practice nurses received ECG training prior to starting ECG clinics.
All patients in the systematic screening arm were sent an invitation to attend a screening clinic along with an information sheet. Non-responders were sent a reminder.
Patients in the opportunistic screening arm had their records flagged to encourage staff to undertake pulse recordings during routine consultation. Patients who had an irregular pulse were given an information sheet and invited to attend a screening clinic.
Screening clinics were run by practice nurses, who took patient histories, checked radial pulse rate and whether it was regular or irregular, and recorded a 12-lead ECG. The patient was then asked to complete a questionnaire on the acceptability of the intervention. All 12-lead ECGs were sent to two cardiologists for reporting. If there was disagreement over the diagnosis a third cardiologist decided. Patients were informed of the results within two weeks.
New cases of atrial fibrillation detected within the 12 month study period
Incremental cost per case detected
Cost-effectiveness of screening in the UK
Community prevalence and incidence of AF
Acceptability of AF screening and patient uptake
|Funding||This research was funded by the NHS research and development health technology assessment programme (No 96/22/11)|
|Notes||Intention-to-treat analysis was performed, patients who already had a diagnosis of AF excluded from the calculation of newly detected cases.|
|Risk of bias|
|Bias||Authors' judgement||Support for judgement|
|Random sequence generation (selection bias)||Low risk||Probably done for control and intervention groups "After stratification for practice size and deprivation (based on Townsend score), we used MINITAB to select randomly two equal size groups from those practices within a particular stratum. We used a simulated value from a Bernoulli distribution, comprising two values equally likely to occur, to determine which group became the intervention arm (the other being the control arm)"|
Also probably done for embedded trial within the intervention arm: "We used SPSS to allocate patients randomly from this list to either systematic or opportunistic screening to create two equal size groups of patients within each stratum so that each strategy (systematic or opportunistic screening) had an equal chance of detecting known, unknown, and suspected atrial fibrillation (n=4933). Which group then became the systematic arm (the other being opportunistic) was again decided by using a simulated value from a Bernoulli distribution, comprising two values equally likely to occur."
|Allocation concealment (selection bias)||Unclear risk||The authors state that "there was no deliberate concealment of allocation to the trial arms...the trial statistician determined allocation, which was implemented by the trial coordinator". However the clusters (GP practices) were identified and recruited before randomisation was conducted, so allocation was concealed from the people providing permission for the cluster to be included in the trial. Similarly, patients in the intervention arm were identified and randomly allocated into two groups before it was known to anyone involved in the trial which group would be allocated to which treatment (opportunistic or systematic), since this was decided at the end of the randomisation process using a simulated value from a Bernoulli distribution, comprising two values equally likely to occur. However since there was no deliberate attempt to conceal allocation it is unclear to what extent a risk of selection bias might have arisen from practices in the intervention arm knowing they were in the intervention arm and not the control arm prior to the recruitment of participants.|
|Blinding of participants and personnel (performance bias) |
|High risk||It was not possible to blind patients, who were notified by letter that they were being offered the opportunity to participate in an AF screening clinic or were encouraged to have their pulse recorded during routine consultation. Neither were primary care physicians and healthcare staff blinded, since the intervention arm received training where they were informed of the importance of detecting AF and its treatment. Practice nurses at screening clinics who took the patients' medical history, pulse and ECG were probably not blinded to whether the patient came from the systematic or opportunistic arm. Blinding is not feasible in a situation where well informed patients who need to decide whether of not they want to avail of screening are a key component of the systematic screening intervention. However since inability to blind a study is not equal to a blinded study, it is classified as high risk. Screening clinics were used to test patients from each group according to the same protocol and with the aid of a 12-lead ECG machine (Biolog).|
|Blinding of outcome assessment (detection bias) |
|Low risk||Blinding was performed where possible; cardiologists who interpreted the 12-lead ECG reading in order to make a diagnosis of AF were blinded as to the allocation of the patient from whom the ECG was taken.|
|Incomplete outcome data (attrition bias) |
|Low risk||After random sampling to identify participants from the cluster-randomised primary care centres, general practices were contacted to exclude people who had died, moved away or were terminally ill. These exclusions were randomly filled from a reserve list of 10% of the practice patients which was randomised at the same time as the original list. Immediately prior to sending screening invitations or flagging notes, the general practices were again contacted to exclude people who had since died, moved or were terminally ill and these exclusions were not replaced, with the numbers in each arm reported. The primary outcome was calculated taking the original figure using an ITT approach. Patients within each group who already had a diagnosis of AF were excluded from the calculation of the primary outcome (new cases detected). This necessitated a review of patient record to identify those with a pre-existing diagnosis. Records for some people in each of the groups were missing and are reported for each group individually. Both patients with AF and those with missing notes were excluded from the calculation of the rate of new cases detected.|
|Selective reporting (reporting bias)||Low risk||All outcomes specified in the trial protocol were reported|
|Other bias||Unclear risk||There is the potential for recruitment bias and contamination in the study. Recruitment bias could have been introduced at the stage where general practitioners were asked to exclude unsuitable patients from the opportunistic and systematic screening arms within the intervention group. Advice was given to exclude those who had died, moved away or were terminally ill from both groups. People who were excluded at this stage were replaced from a back-up list of patients that had been randomised at the same time as the groups. No data are provided about how many from each group were replaced at this stage, nor is the breakdown of the reasons for their exclusion given. Immediately prior to the intervention GPs were again asked to exclude any patients who had died, moved away or were terminally ill from both groups. Data concerning exclusions at this stage are reported and there was a considerable difference in the numbers excluded between the two arms; 500 were excluded from the systematic screening arm (10% of the total) and 195 (4% of the total). However the individual reasons for exclusion from the systematic screening arm are also reported and only a small minority of these (9 people, 0.2% of total) were deemed unsuitable, as opposed to having died or moved away (491people, 9.9% of total). An ITT analysis was performed that included patients that were removed from the intervention group at this stage in the calculation of the primary outcome.|