Randomisation (2009-20)
When randomisation ended, some 20,000 clusters of women aged 47-49 had been randomly allocated to be invited or not for one additional screening about 3 years before the first of their 7 routine invitations. Likewise, some 20,000 clusters of women aged 71-73 had been randomly allocated to be invited or not for one additional screening about 3 years after the last of their 7 routine invitations (Figure 1).
Randomisation procedures
Women were included in AgeX if they were aged 47-49 or 71-73 and registered with at GP surgery covered by a breast screening unit participating in the study. (Around five-sixths of breast screening units participated in AgeX).
The routine screening programme used a national database to create screening invitation batches, perhaps every few weeks, for each local breast screening unit. An invitation batch typically listed several hundred women of appropriate age (usually 50-70 if not participating in AgeX and 47-73 if participating) who were recorded as currently registered with a particular general practice or living in the locality (eg, one village, or one part of a town) where the breast screening unit was currently working. As each particular locality would not be covered again for about 3 years, the first routine invitation should have occurred at age 50-52 and the last at age 68-70.
The program that generated these batches was updated during 2016-18 to use each woman’s exact age in completed years. (Before then it had used an estimate of age obtained by subtracting the year of birth from the current year: for details, see Annex 3). In batches prepared for AgeX, the program identified new entrants into AgeX, who were those in the cluster aged 47-49 and those in the cluster aged 71-73.
As each batch was being prepared for AgeX, the program preparing it randomly allocated (with equal 50:50 probability and no stratification) either AgeX entrants aged 47-49 or those aged 71-73 to be invited for screening, as shown in Figure 1. The women aged 50-70 were unaffected by the random allocation of the batch; they were invited as normal, and were not new entrants into AgeX.
Lists of those randomised were forwarded to the AgeX investigators, after complete removal by the NHS of any invitees or controls who had previously opted out of having their NHS records used for research or who had been classified as unsuitable for a screening invitation (perhaps because of bilateral mastectomy or a record of having recently been screened).
Each participant entered AgeX on the date her screening batch was created and, simultaneously, randomised; invitations generally went out a few weeks later. New entrants in the batch who had been randomly allocated not to be invited joined AgeX as controls.
Trial participant information
Screening units informed local general practitioners that AgeX was taking place in their area, and a poster about AgeX (Annex 4) was provided for them to display in their surgery. Otherwise, the controls were not individually notified.
Where randomisation into AgeX was in progress, women of any age who were being sent an invitation for screening all received the standard NHS screening brochure plus the AgeX participant information sheet (Annex 5), which said that if they were aged 50 to 70 then they could ignore the leaflet. It also said that if they were younger than 50 or were 71 or older then they were being sent the invitation (which they were free to ignore) as part of a trial of breast screening in which their de-identified routine NHS records would be analysed by researchers at the University of Oxford.
Consent and confidentiality
Section 251 approval for including women in AgeX without consent and for the use of patient-identifiable data without consent was obtained initially from the UK National Information Governance Board for Health and Social Care, then annually from it and any successor (currently the Health Research Authority Confidentiality Advisory Group, CAG). With respect to consent for screening, the standard procedures of the NHS breast screening programme applied, whereby attending screening was taken as implied consent.
Linkage of individual records is to routinely collected data, currently held centrally by NHS England. AgeX is conducted in accordance with all relevant aspects of CAG, General Data Protection Regulation, and the Data Protection Act requirements. All datasets continue to be treated appropriately, held securely, used only for medical research, and analysed only in de-identified form. Further details of data handling and security are provided in Annex 2.