Establishment of RWS guidance reflecting contributions of China to regulatory science.

China's accession to the ICH has accelerated the advancement of its regulatory science. To foster innovation and improve the efficiency of pharmaceutical research and development, the China National Medical Products Administration (NMPA) encourages the use of real-world evidence (RWE) to support drug regulatory decision-making and has constructed a series of real-world study (RWS) related guidance, reflecting the contribution of the NMPA to the field of RWS in drug clinical development. Based on the four guidelines on RWE, real-world data (RWD), RWS design and protocol development, and communication with regulatory authorities, the guidance has been extended to more specific clinical applications, such as oncology, rare diseases, pediatric drugs, and traditional Chinese medicine. This paper reviews the core content and features of the series of RWS guidelines, presents their role in promoting drug development, and discusses challenges of using RWE in support of drug regulatory decision-making in China.

Effect of folic acid supplementation on preterm delivery and small for gestational age births: A systematic review and meta-analysis.

OBJECTIVE: To investigate the effect of folic acid (FA) supplementation on the risks of preterm delivery (PTD) and small for gestational age births (SGA). DATA SOURCES: Cohort studies were identified from MEDLINE, EMBASE, the Cochrane Library, CINAHL, and CBM from inception to January 2015. PARTICIPANTS AND INCLUDED STUDIES: Healthy women who want to get pregnancy or being pregnant. MAIN OUTCOME MEASURES: PTD and SGA. RESULTS: The association of FA and PTD was significant when supplement initiated after pregnancy (RR=0.68, 95%CI, 0.52-0.90), whereas no effect was founded if the initiation time was before conception (RR=0.89, 95%CI, 0.80-1.01). The results for the association between FA supplementation and SGA showed significant protective effect: initiated before conception (RR=0.70, 95%CI, 0.57-0.85) and initiated after conception (RR=0.84, 95%CI, 0.81-0.89). CONCLUSION: Folic acid supplementation is associated with a significant reduction on the risk of PTD when initiated after conception. It can also protect fetus from SGA.

Folic acid supplementation, preconception body mass index, and preterm delivery: findings from the preconception cohort data in a Chinese rural population.

BACKGROUND: Folic acid (FA) supplementation before and during the first trimester can reduce the risk of occurrence of preterm delivery (PTD). Preconception body mass index (BMI) is also associated with PTD. This study aimed to investigate the combined effect of FA supplements and preconception BMI on the risk of PTD. METHODS: The data of a cohort from 2010-2011 that was obtained through a preconception care service in China was used (including 172,206 women). A multivariable regression model was used to investigate the association between maternal preconception conditions and the risk of PTD. The interaction of preconception BMI and FA supplementation was measured by a logistic regression model. RESULTS: Taking FA supplements in the preconception period or in the first trimester reduced the risk of PTD (odds ratio [OR] = 0.58 and OR = 0.61, respectively). Women with an abnormal BMI had an increased risk of PTD (OR = 1.09, OR = 1.10, and OR = 1.17 for underweight, overweight, and obese, respectively). Preconception BMI showed an interaction with the protective effect of FA supplementation for PTD. With regard to the interaction of FA supplementation, the adjusted odds ratio (aOR) was 0.57 (95% CI: 0.51, 0.64) in underweight women, 0.85 (95% CI: 0.73, 0.98) in overweight women, and 0.77 (95% CI, 0.65, 0.91) in obese women. Preconception BMI also showed an interaction with the time of FA supplementation. Women with a normal BMI who began to take FA supplements in the preconception period had the lowest risk of PTD (aORs: 0.58 vs. 0.65 beginning in the first trimester). The aORs at preconception and the first trimester in the underweight group were 0.56 vs. 0.60. The aORs at preconception and the first trimester were 0.94 vs. 0.65 and 1.15 vs. 0.60 in the overweight and obesity groups, respectively. CONCLUSIONS: In our study, FA supplements reduced the risk of PTD, while abnormal BMI raised the risk of PTD, although higher BMI categories did not have this higher risk once adjusted analysis was conducted. The protective effect of FA supplementation for PTD was reduced in women with overweight or obesity. To get better protection of FA supplementation, women with normal BMI or underweight should begin to use in preconception, while women with overweight or obesity should begin to use after conception.