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
Authors: Stephen Kaptoge, Emanuele Di Angelantonio, Carmel Moore, Matthew Walker, Jane Armitage, Willem H Ouwehand, David J Roberts, John Danesh, Simon G Thompson, Stephen Kaptoge, Emanuele Di Angelantonio, Carmel Moore, Matthew Walker, Jane Armitage, Willem H Ouwehand, David J Roberts, John Danesh, Simon G Thompson, Jenny Donovan, Ian Ford, Rachel Henry, Beverley J Hunt, Bridget le Huray, Susan Mehenny, Gail Miflin, Jane Green, Mike Stredder, Nicholas A Watkins, Alan McDermott, Clive Ronaldson, Claire Thomson, Zoe Tolkien, Lorna Williamson, David Allan, Jennifer Sambrook, Tracey Hammerton, David Bruce, Fizzah Choudry, Cedric Ghvaert, Kirstie Jonston, Anne Kelly, Andrew King, Alfred Mo, Lizanne Page, Penny Richardson, Peter Senior, Yagnesh Umrania, Henna Wong, Brendan Burchell, John Gallacher, Gavin Murphy, Adrian C Newland, Keith Wheatley, Michael Greaves, Marc Turner, Tahir Aziz, Richard Brain, Christine Davies, Ruth Turner, Paula Wakeman, Alison Dent, Alan Wakeman, Ben Anthony, Desmond Bland, Willem H Parrondo, Helen Vincent, Candy Weatherill, Andrea Forsyth, Carol Butterfield, Tracey Wright, Karen Ellis, Kristie Johnston, Pat Poynton, Carolyn Brooks, Emma Martin, Lara Littler, Lindsay Williamson, Donna Blair, Karen Ackerley, Lynn Woods, Sophie Stanley, Gemma Walsh, Gayle Franklin, Cheryl Howath, Sarah Sharpe, Deborah Smith, Lauren Botham, Caroline Williams, Claire Alexander, Gareth Sowerbutts, Diane Furnival, Michael Thake, Shilpa Patel, Carolyn Roost, Sandra Sowerby, Mary Joy Appleton, Eileen Bays, Geoff Bowyer, Steven Clarkson, Stuart Halson, Kate Holmes, Gareth Humphreys, Lee Parvin-Cooper, Jason Towler, Joanne Addy, Patrica Barrass, Louise Stennett, Susan Burton, Hannah Dingwell, Victoria Clarke, Maria Potton, Thomas Bolton, Michael Daynes, Stuart Halson, Sarah Spackman, Michael Walker, Abudu Momodu, James Fenton, Adam King, Omer Muhammad, Nicholas Oates, Tim Peakman, Christine Ryan, Kristian Spreckley, Craig Stubbins, Joanna Williams, James Brannan, Cedric Mochon, Samantha Taylor, Kimberly Warren, Stephen Kaptoge, Emanuele Di Angelantonio, Jonathan Mant, Willem H Ouwehand, Simon G Thompson, John Danesh, David J Roberts
Journal: The Lancet Haematology (2019)

BackgroundThe 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.MethodsThe 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.FindingsBetween 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).InterpretationDuring 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.FundingNHS Blood and Transplant, UK National Institute for Health Research, UK Medical Research Council, and British Heart Foundation.