Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Abstract

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries.

Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants.

Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59-1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69-0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76-0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39-0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups.

Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency.

Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation.

Figure 1

Trial profile CONSORT flowchart showing recruitment, participation, and completeness of main outcomes. *Participants withdrew permission to use their data. †Physical wellbeing at 2 years was measured with the physical component score (PCS) of the 36-item Short Form Health Survey, version 2 (SF-36v2).

Figure 2

Number of whole blood donations during the 2-year trial period and in the previous 2 years by sex and intervention group The p values compare randomised groups (shown in red) adjusted for baseline characteristics (centre, age, weight, and new donor status). Mean (95% CI) numbers of whole blood donations made by the same individuals in the 2 years before the trial (shown in blue) are provided for context. Minimum inter-donation intervals allowed before the trial were 12 weeks for men and 16 weeks for women.

Figure 3

Self-reported symptoms during the 2-year trial period by sex and intervention group The p values assess trends across randomised groups, adjusted for baseline characteristics (centre, age, weight, and new donor status).

Figure 4

Number of whole blood donations in prespecified subgroups Mean (95% CI) numbers of whole blood donations during the 2-year trial period are shown for men (A) and women (B). Continuous baseline variables are presented in quintile groups. p values correspond to tests for continuous interaction with randomised group. Analysis by ferritin concentration was not prespecified.