Decrease in blood donation rates in Japan: a time series analysis

: Objective: To clarify that one of the causes for the decrease in blood donation (BD) rates was the introduction of the 400 ml BD program in 1986. Method: BP rates were monitored over 48 years (1965–2012) and were divided into pre- and post-intervention periods prior to analysis. An interrupted time series analysis was performed using annual data on BD rates, and the impact of the 400 ml BD program was investigated. Results: In a raw series, autoregressive integrated moving average analysis revealed a significant change in slope between the pre- and post-intervention periods in which the intervention factor was the 400 ml BD program. The parameters were as follows: intercept (initial value) = 0.315, confidence interval (CI) = (0.029, 0.601); slope (pre-intervention) = 0.316, CI = (0.293, 0.340); slope difference = -0.435, CI = (-0.462, -0.408); slope (post-intervention) = -0.119, CI = (-0.135, -0.103); all, p = 0.000; goodness-of-fit, R 2 = 0.963. After adjusting for stationarity and autocorrelation, the parameters were as follows: intercept (initial value) = -0.699, CI = (-0.838, -0.560); slope (pre-intervention) = 0.136, CI = (0.085, 0.187); slope difference = -0.165, CI = (-0.247, -0.083); slope (post-intervention) = -0.029, CI = (-0.070, 0.012); all, p = 0.000 (except for slope (post-intervention), p = 0.170); goodness-of-fit, R 2 = 0.930. Conclusion: One of the causes for decrease in BD rates may be due to the introduction of the 400 ml BD program in Japan.


INTRODUCTION
In Japan, blood donations, which are only conducted by the Japanese Red Cross Society, began in 1965 (one donation volume: 200 ml) and are used for treating diseases and injuries 1 . Therefore, it is important to ensure a stable supply of blood. Considering the physical fitness and nutritional status of the Japanese in 1965, the blood donation volume was determined to be 200 ml once, which was about half that of developed countries in Europe and the United States. The volume was corrected to 400 ml in 1986, due to the improvement of Japanese physical strength and nutritional status.
Many studies have shown that blood donation rates are an index to measure the level of social capital [2][3][4] . Starting in the late 1980s, blood donation rates have continued to decline in Japan 5 , which prompted the view of declining altruism 6 . However, only a few studies have shown that factors other than altruism are related to blood donation rates 7 .
This study focused on the cause for decrease in blood donation rates. Thus, the blood donation rate was investigated using an interrupted time series (ITS) analysis [8][9][10][11] . The possible cause hypothesized for decrease in blood donation rates was the introduction of the 400 ml blood donation program in 1986.

DATA ANALYSIS OF CLINICAL QUALITY MEASUREMENT
ITS is an analysis used to observe long-term phenomena and evaluates changes due to certain interventions [13][14][15] . The following linear regression model is used to estimate the level and trend in the dependent variable before intervention, as well as changes in the level and trend following intervention (Equation 1): Y t = β 0 + β 1 ×time before intervention t + β 2 ×intervention t +β 3 ×time after intervention t + e t (1) In which: Yt = the outcome, t = time in years at time t from the start of the observation period to the last time point in the series.
All "t" is the number of years elapsed since 1965, which was set to 0. Furthermore, intervention is a measure of time t specified as a dummy variable in which the value is 0 (when occurring before intervention) and 1 (when occurring after intervention) and was implemented in the series. In this model: β 0 = the baseline level of outcome at the beginning of the series; β 1 = the slope prior to intervention; β 2 = the change in the level immediately after intervention (pre-intervention = 0, post-intervention = 1); β 3 = the change in slope from pre-to post-intervention; β 1 + β 2 = the post-intervention slope; e t = the random error term.

STATISTICAL ANALYSIS
Firstly, the ITS data (raw data: between 1956 and 2012) was analyzed using auto regressive moving average model (ARIMA (p, d, q)) 16 . Secondly, if there was non-stationarity, autocorrelation 17 , or seasonality, the data were re-adjusted and re-analyzed. At the time of analysis, stationarity in the raw series was evaluated using Dickey-Fuller test with no divergence. Durbin-Watson statistic was then used to check for autocorrelation. Next, data were collected (between 1965 and 2012 over 48 years), a sufficiently large number of data to verify the seasonal variation. Finally, Pearson's correlation coefficient was used to analyze the correlation between the donation rate and the number of blood donors (400 mL), and the total donation volume was clarified. Modeling and statistical tests were carried out using SPSS 25 (USA) and XLSTAT 2018.5 (USA).
The Shikoku Medical College Ethic Screening Committee determined that medical ethical approval was not required since all the data used in this study was already officially released.
Second, we found that the raw series was stationarity using the Dickey-Fuller test without divergence. Since the time series plot of blood donation rate did not diverge, it was considered that the donation rate was either "having unit root" or "satisfying stationarity". Here, as it was found by the Dickey-Fuller test that the blood donation rate had "no unit roots", it could be judged that the donation rate satisfied the stationarity legally. It was also confirmed that the raw series was autocorrelated using Durbin-Watson statistics. Since seasonality was not established, the raw series was converted to a logarithmic series and a single moving average was obtained. The adjusted model was ARIMA (1, 0, 0) with the following parameters: intercept  (Table 3). Therefore, an increase and decrease in blood donation rates was observed before and after intervention, respectively. Finally, Pearson's correlation coefficient was used to analyze the correlation between the donation rate and number of blood donors (400 mL) and was found to be -0.9480 (p < 0.001). The total donation volume between 1986 and 2012 was nearly constant every year (1,845,000 (minimum) -2,167,000 liters (maximum)) ( Table 4).

DISCUSSION
ITS analysis is a powerful quasi-experimental design for assessing the longitudinal impact of an intervention. In this study, the intervention was the 400 mL blood donation program introduced in 1986. Using this analysis, our results suggest that one of the causes for decrease in blood donation rates may be due to the introduction of the 400 mL blood donation program in Japan.  Table 3. Interrupted time series analysis (adjusted; ARIMA (1, 0, 0)).
Based on our analysis, the donation rate consistently increased between 1965 and 1985 prior to the 400 mL blood donation program. The slope of the fitted line was 0.316 (adjusted, 0.136). However, the donation rate consistently decreased between 1986 and 2012 after the 400 ml blood donation program was implemented. The slope of the fitted line was -0.119 (adjusted, -0.029). This suggests that the blood donation rate may have decreased due to the 400 ml blood donation program. In this study, the slope after the intervention presented significant difference in the ARIMA (0, 0, 0) model (Table 2) and no significant difference in the ARIMA (1, 0, 0) model (Table 3). In addition, ARIMA (0, 0, 0) model (R 2 = 0.963) was more fit than ARIMA (1, 0, 0) model (R 2 = 0.930). This was probably because ARIMA (1, 0, 0) model had excessively incorporated the rise in blood donation rates since 2009 on into the model, causing goodness-of-fit to decrease. There is also a strong inverse correlation between the decrease in the blood donation rate and increase in the number of 400 ml blood donations (Pearson's correlation coefficient = -0.9480, p < 0.001). This result suggests that the implementation of the 400 ml blood donation program may have decreased the blood donation rate. Furthermore, despite the decrease in blood donation rate, the total donation volume between 1986 and 2012 was nearly constant every year. Therefore, there was no risk of shortage in blood supply.