Longer-term efficiency and safety of increasing the frequency of whole blood donation (INTERVAL): extension study of a randomised trial of 20 757 blood donors

Abstract

Background: The INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet blood shortages. We extended the INTERVAL trial for a further 2 years to evaluate the longer-term risks and benefits of varying inter-donation intervals, and to compare routine versus more intensive reminders to help donors keep appointments.

Methods: The INTERVAL trial was a parallel group, pragmatic, randomised trial that recruited blood donors aged 18 years or older from 25 static donor centres of NHS Blood and Transplant across England, UK. Here we report on the prespecified analyses after 4 years of follow-up. Participants were whole blood donors who agreed to continue trial participation on their originally allocated inter-donation intervals (men: 12, 10, and 8 weeks; women: 16, 14, and 12 weeks). They were further block-randomised (1:1) to routine versus more intensive reminders using computer-generated random sequences. The prespecified primary outcome was units of blood collected per year analysed in the intention-to-treat population. Secondary outcomes related to safety were quality of life, self-reported symptoms potentially related to donation, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin and other factors. This trial is registered with ISRCTN, number ISRCTN24760606, and has completed.

Findings: Between Oct 19, 2014, and May 3, 2016, 20 757 of the 38 035 invited blood donors (10 843 [58%] men, 9914 [51%] women) participated in the extension study. 10 378 (50%) were randomly assigned to routine reminders and 10 379 (50%) were randomly assigned to more intensive reminders. Median follow-up was 1·1 years (IQR 0·7-1·3). Compared with routine reminders, more intensive reminders increased blood collection by a mean of 0·11 units per year (95% CI 0·04-0·17; p=0·0003) in men and 0·06 units per year (0·01-0·11; p=0·0094) in women. During the extension study, each week shorter inter-donation interval increased blood collection by a mean of 0·23 units per year (0·21-0·25) in men and 0·14 units per year (0·12-0·15) in women (both p<0·0001). More frequent donation resulted in more deferrals for low haemoglobin (odds ratio per week shorter inter-donation interval 1·19 [95% CI 1·15-1·22] in men and 1·10 [1·06-1·14] in women), and lower mean haemoglobin (difference per week shorter inter-donation interval -0·84 g/L [95% CI -0·99 to -0·70] in men and -0·45 g/L [-0·59 to -0·31] in women) and ferritin concentrations (percentage difference per week shorter inter-donation interval -6·5% [95% CI -7·6 to -5·5] in men and -5·3% [-6·5 to -4·2] in women; all p<0·0001). No differences were observed in quality of life, serious adverse events, or self-reported symptoms (p>0.0001 for tests of linear trend by inter-donation intervals) other than a higher reported frequency of doctor-diagnosed low iron concentrations and prescription of iron supplements in men (p<0·0001).

Interpretation: During a period of up to 4 years, shorter inter-donation intervals and more intensive reminders resulted in more blood being collected without a detectable effect on donors' mental and physical wellbeing. However, donors had decreased haemoglobin concentrations and more self-reported symptoms compared with the initial 2 years of the trial. Our findings suggest that blood collection services could safely use shorter donation intervals and more intensive reminders to meet shortages, for donors who maintain adequate haemoglobin concentrations and iron stores.

Funding: NHS Blood and Transplant, UK 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 in the extension study. *Participants who were randomised but later withdrew consent for any further use of their data. †Due to staggered roll-out of the main 2-year trial, only participants expected to attend at least two more sessions were considered eligible for invitation to the extension study. ‡Participants not consenting to the extension study reverted to routine NHS Blood and Transplant reminders (men every 12 weeks, women every 16 weeks). §Number for whom a physical component score could be calculated at the end of the extension trial. ¶Number who provided a research blood sample at the end of the extension trial from which haemoglobin and ferritin were measured. ||Number who responded to at least one question in any of the 6-monthly questionnaires administered during their participation in the extension study.

Figure 2

Whole blood donation rate during the main trial and in the extension study by sex and inter-donation intervals All participants in the main trial were allocated to active reminders. Participants not included in the extension study automatically reverted to standard inter-donation intervals (12 weeks for men, 16 weeks for women) at their completion of the main trial, with anonymised lookup of blood donation information from NHS Blood and Transplant records made possible by consent given at the beginning of the main trial. The blood donation rates for these participants during the period of the extension study are shown according to the original randomised groups, purely for comparison purposes, even though they had all reverted to the standard inter-donation intervals. Error bars denote 95% CI. *Allocated to routine reminders in the extension study. †Allocated to active reminders in the extension study.

Figure 3

Whole blood donation rates during the extension study, the main trial period, and in the previous 2 years by sex and inter-donation intervals The p values compare across inter-donation intervals and are adjusted for baseline characteristics (centre, age, weight, new donor status). Minimum inter-donation intervals allowed before the trial were 12 weeks for men and 16 weeks for women. Error bars denote 95% CI.

Figure 4

Haemoglobin (A) and ferritin (B) concentrations at the end of the extension study, end of the main trial period, and at baseline by sex and inter-donation intervals Analysis is restricted to participants in the extension study. The p values assess trends across inter-donation intervals, adjusted for baseline characteristics (centre, age, weight, new donor status, and haemoglobin [A] or log_e ferritin [B]). Error bars denote 95% CI.