Study design, setting and participants
The Guangzhou Blood Center is one of the largest blood centres in China along with the Beijing and Shanghai Centers. A total of 263,681 donors donated blood during 2014, of which 179,964 (68.3%) then became inactive and 83,717 (31.7%) donated again before 2016 [27].
This single-centre, non-blinded parallel randomized controlled trial involved two intervention groups (telephone or SMS reminders) and a no-intervention control group. Figure 1 shows a flow chart of the study design. During the experiment period, donors who had donated blood after July 1, 2014 were continuing to receive phone call and/or SMS reminders occasionally from Guangzhou Blood Center. Therefore, in order to avoid contaminations, both whole blood and apheresis platelet donors whose last donations were between January 1 and June 30, 2014 were eligible for the screening. The age range for blood donors in mainland China is 18-55 years. Those aged above 50 years old were excluded from the screening based on the previous finding that most older individuals are unlikely to donate again due to physical reasons [28]. All data were provided by the Guangzhou Blood Center through the Blood Donation and Supply System [27].
The calculated sample size needed for each group was 2,252 [29], and in order to better detect significant differences and balance the sample size in each tier, the actual sample size was 3,960 in each group (11,880 total). All participants were stratified into 18 tiers by age (20-30, 31-40, and 41-50 years), gender (male and female), and frequency of prior donation, which refers to number of times a donor donated before becoming inactive (one time, two or three times, and four times or more). Based on a computer-generated list of random numbers, the first 220 eligible participants in each tier were assigned to the telephone group, the 221st to 440th were assigned to the SMS group, and the 441st to 660th were assigned to the control group.
Interventions and endpoint
The experimental period lasted from October 20 to November 10, 2016. The details of the recruitment method were described in the pilot study [29]. The start time was set at the day that an intervention was made.
Telephone call reminder
Telephone interviews were conducted over a 1-month period by two interviewers (O-Y and BEI, staff members at the Guangzhou Blood Center with the responsibility of blood donor recruitment). The interviews were conducted using pre-designed questionnaires and lasted 2.4-21.3 min (mean±SD, 4.8±1.2 min). Prior to this study, the interviewers summarized the barriers to donation frequently mentioned by participants in the pilot study [29], discussed the challenges that arose during the interviews, reviewed the optimal response techniques, and practiced via role playing to ensure adherence to the script.
Donors who could not be reached by telephone because the phone number was wrong were marked as non-responders. Donors with a disconnected phone line or who did not answer were called two more times on subsequent days before being classified as “no answer”. Donors who answered the phone but refused the interview request were marked as “refusal”. All participants, including those marked as non-responders, no answer, and refusal, were further followed up as described below. After contact was successfully made, a brief and scripted interview was delivered with the donors’ permission (Additional file 1).
SMS reminder
In the SMS group, participants received a text message making an altruistic appeal. As follow:
“Dear donors,
Thank you for your donation through which your love brought hope to those helpless patients and your donated blood reignited the fire in their lives. If you can, please consider donating blood again to save a life.
Thank you again for your support!”
The message was sent via the SMS platform of the Guangzhou Blood Center. Message receipts, which stated if a message was received successfully or not were retrieved from the SMS platform within 48 hours. All participants, whether they received the message or not, remained on the list for further follow-up as described below.
Follow-up and outcome measures
The donation activity of each participant was followed for 365 days from the recruitment day. All participants could be followed via the Blood Donation and Supply System in which their blood donation records in Guangzhou could be checked. The primary outcome was to identify the occurrence of the first next blood donation attempt among all participants within the 1-year follow-up and evaluate the return rates according to donor characteristics (gender, age and past donation frequency). A participant was classified as a re-activated donor if he/she made at least one subsequent donation by the end of the 1-year follow-up period; otherwise, the donor was classified as “no return”. The secondary outcomes were the main self-reported reasons for deferral given by donors during the telephone calls. Other outcomes included the re-donation interval for each group after recruitment, the efficacy of each intervention, and the cost-effectiveness of telephone calls versus SMS reminders on re-recruitment.
Statistical analysis
The database and foundation for analyses were established by recoding data in an Excel software (2013, Microsoft Corporation, Redmond, WA, USA) file and importing into the Statistical Package for Social Sciences software (SPSS Statistics version 23 for Windows, SPSS Inc., Armonk, NY, USA) and The R Project for Statistical Computing (R version 3.6.1). For intention-to-treat (ITT) analysis, the re-donation rate was calculated by dividing the number of participants who donated again during the follow-up period by the corresponding number of initially randomized donors. Because of the large disparity in the intervention received rates between the two interventional groups, the ITT result might have masked a true effect on the re-donation rate among those who received reminders as intended. Therefore, estimation of the effects of the interventions on inactive blood donors while accounting for compliance with assigned intervention was also conducted. Previous studies defined four compliance types on the basis of individuals’ treatment assignment status and potential treatment receipt status [30-32]. In this study, strict adherence to the intervention assignment meant that those in the control group did not receive any telephone call or SMS message; meanwhile, participants in the telephone group did not receive an SMS message and vice versa. Thus, in this case, there were no directly observed always-takers (defined as those who will always implement the treatment, regardless of the group to which they are assigned), nor defiers (defined as those who will not implement if assigned to the treatment group but will implement if assigned to the control group). The participants did include compliers (defined as those who will implement the treatment when assigned to the treatment group but will not implement if assigned to the control group) and those could still be never-takers (defined as those who will never implement, regardless of the treatment assignment). In other words, this was a one-sided non-compliance situation, with only compliers (who received the telephone or SMS reminders successfully in the intervention groups, and who were in the control group) and never-takers (who failed to receive the telephone or SMS reminders in the intervention groups) [33]. Therefore, the average treatment effect on the treated (ATT) were also estimated [33].
Chi-square test was used to identify statistical differences of the re-donation rate among groups and conduct paired comparisons between contact methods, and Bonferroni correction was applied. R Package “ATE” was used to estimate the ATT the ATT among compliers under the intervention and control conditions (random assignment was used as an instrumental variable that telephone or SMS group coded as 1, control group coded as 0; complier in the telephone or SMS group was coded as 1, never-taker and those in the control group were coded as 0).
The Kruskal-Wallis test was used to determine whether the re-donation intervals within 30, 90, 180, 270 and 365 days were affected by different reminders, and Mann-Whitney U test was applied for comparisons of two groups. Binary logistic regression analyses were adopted to identify associations of donor characteristics with donor return behaviour to determine the best predictors of future donation; odds ratio (ORs) and 95% confidence intervals (CIs) were calculated. The incremental cost-effectiveness ratio (ICER) was applied to compare the cost-effectiveness of telephone calls and SMS reminders. All hypothesized differences were considered statistically significant if the P-values from two-tailed tests were < 0.05.
Ethics considerations
All procedures were reviewed and approved by Institutional Review Board of the Guangzhou Blood Center. The registration ID for this study on ClinicalTrial.gov is: NCT03366441. This study is reported according to the CONSORT guidelines (Additional file 2).