Objective Inappropriate drug dosage is a serious problem in pediatrics, mainly due to the lack of clinical evidence in children, suitable preparation formulation, and standardized methods for dose adjustment. A method for evaluating and monitoring appropriate dosage in pediatrics is urgently needed. The drug utilization index (DUI) based on the Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) has been widely used in the assessment of appropriate dosage in adults. We explored possible methods for assessing appropriate dosage in children. Methods Based on our previous studies, we discuss cDUI in the assessment of appropriate dosage in children as follows: the meaning of cDDD, the establishment of a standardized system, and the classified evaluation of dosage in pediatrics. Results Although the definition of cDDD draws on the concept of defined daily dose (DDD), the meaning of cDDD is different from that of the latter. Specifically, the purpose of cDDD is to evaluate appropriate pediatric dose, while DDD is a unit of measurement. cDDD could be used to assess dose rationality for common and serious pediatric diseases, and would be refined over time. A single cDDD should be assigned per drug and indication and given per drug and route of administration. The influence of age, weight, diagnosis, and administration route on the dosage should be considered. Classified evaluation should be used and weight should be given to the above mentioned factors in order to evaluate the appropriate dose objectively and comprehensively. Conclusion Dosage regulation in pediatrics has an important role in improving medical quality and protecting the safety, effectiveness, and economy of medical therapy in children. The establishment of a cDUI system is a good try in pediatric dosage evaluation. Although there are still defects within this proposed system and methodology, the principle seems feasible.
ObjectiveThis study aims to compare different references for the fetal risk of drugs used in pregnancy to provide evidence for the safety of drug use in pregnancy.MethodsFour drug databases, including Lexicomp, Micromedex, TERIS, and Reprotox, as well as two books of drugs in pregnancy edited by Briggs and Schaefer, were searched. Descriptive analysis was performed regarding the definition of pregnancy recommendations and the specific content of medication.ResultsThe six references employed slightly different approaches to drugs in pregnancy, however, all of them included summaries of the risk in pregnancy, data of crossing the placenta, and human and animal data. The databases of Micromedex, TERIS, and a book edited by Briggs had their risk classification systems for drug use during pregnancy. For specific drugs, the summary of different information in pregnancy was different, the amount and content of listed evidence varied, and there was no evaluation of the quality and relevance of evidence among the references.ConclusionsThere is no consensus on the risk assessment of drugs in pregnancy. Risk classification systems for drugs in pregnancy are still an important method for determining the fetal risk of drugs. The existing references merely list studies of drugs in pregnancy, without comprehensive quality assessment. A methodological study of assessment of the risk of drugs in pregnancy is required.
Objective To assess the global situation of off-label drug use in outpatient children.Methods A search was conducted in PubMed, EMbase, CBM, CNKI and VIP for collecting studies on off-label drug use in outpatient children aged 0 to 18 years, and the publication language was limited to English and Chinese. The quality assessment was based on Crombie Criteria for cross-sectional studies, and the descriptive analysis was performed to analyze the incidence of off-label drug use at all levels of medical institutes and different age groups, the common types of off-label used drugs, and the constitution ratio of off-label use drugs. Results A total of 20 cross-sectional studies were included, involving 1 933 760 children and 5 262 573 prescriptions. The results of descriptive analysis showed: a) The incidence of off-label drug use in outpatient children in primary care and tertiary care institutes were 19.5% (IQR 13.5%, 24.5%) and 26.0% (IQR 24.0%, 35.0%), respectively; b) The primary studies reported that neonate, infant and adolescent had the highest incidence of off-label drug use, while the other children had the lowest incidence; c) Drugs for respiratory system, anti-infection, sensory organs, and dermatosis were listed as the top 5 frequently used off-label drugs by more than half of the studies; d) The studies with issue of “lack of instruction for children” showed it was exactly the type with highest incidence of off-label use, while other studies without that issue showed the highest incidence was over aged off-label use. Conclusion a) Off-label drug use is common in outpatient children. The incidence of off-label drug use may be higher in tertiary care institutes than primary care institutes, and it is higher in neonate, infant and adolescent rather than other age groups of children; b) Incidence of off-label use may be higher in inpatient children than outpatient ones; c) Drugs for respiratory system, anti-infection, sensory organs, and dermatosis were most common types of off-label use; and d) Off-label use due to both “lack of instruction for children” and “over aged use” is more common. So it suggests that further studies trials should focus on fields in which clinical trials of drugs are totally absent.
Objective To provide evidence for the definition, current development and prospect of Evidence-based pharmacy through systematically assessing the extant literatures. Methods We searched CBM, VIP, CNKI, PubMed, EMbase, and Google for supplement. We extracted definitions of evidence-based pharmacy, types of studies, published year, topics of studies, and the author information from the included studies. We compared the definitions on different domains, and assessed the current development of evidence-based pharmacy literature. Results a) The definition of evidence-based pharmacy: We found 4 definitions, and there were great differences among them on the people who practiced evidence-based pharmacy as well as the methods and areas of the practice. b) The evidence-based pharmacy literature: 12 English and 202 Chinese articles were included in the review. The number of Chinese evidence-based pharmacy articles was increasing annually, especially in recent 3 years; Most of their authors were from hospitals, especially from pharmacy department; Their study orientations mostly involved clinical pharmacy and hospital pharmacy; The topics mainly refered to the practice and development of clinical pharmacy, rational drug use, and development of hospital pharmacy. Conclusion a) There is yet no consensus on the definition of evidence-based pharmacy. b) Few researchers worldwide know or show interest in evidence-based pharmacy, while, so far, more and more researchers are getting to know evidence-based pharmacy in China. c) Further efforts should be made to develop the theoretical system of evidence-based pharmacy and the pattern of its practice.
ObjectiveTo systematically review the safety of low molecular weight heparin (LMWH) in pregnancy. MethodsPubMed, EMbase, The Cochrane Library, WanFang Data, VIP, and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) and cohort studies on the safety of LMWH in pregnancy from inception to March 30th, 2020. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Meta-analysis was then performed using RevMan 5.3 software. ResultsA total of 77 RCTs and 13 cohort studies were included. The results of meta-analysis showed that LMWH increased the incidence of postpartum hemorrhage (RR=1.50, 95%CI 1.00 to 2.25, P=0.05). However, there was no significant difference. The incidence of hematological adverse events was different from the results of RCTs and cohort studies. The results of RCT subgroup analysis showed that LMWH increased ecchymosis at the injection site (RR=1.60, 95%CI 1.24 to 2.08, P=0.000 4). However, the incidence of overall skin system adverse events did not increase significantly. LMWH reduced the incidence of cardiovascular adverse events (RR=0.18, 95%CI 0.07 to 0.46, P=0.000 3). LMWH failed to increase the occurrence of fetal congenital malformations, digestive system, central nervous system, skeletal system, and systemic adverse events. ConclusionsCurrent evidence suggests that LMWH is relatively safe to use during pregnancy. However, whether it increases postpartum hemorrhage and hematological adverse events is unclear. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions.
Objective To assess the global situation of off-label drug use in hospitalized children. Methods The databases such as PubMed, EMbase, CBM, CNKI and VIP were searched to collect studies on off-label drug use in hospitalized children at age of 0 to 18 years old. The publication language was limited to English and Chinese. The quality assessment was based on Crombie Criteria for cross-sectional studies. The incidence of off-label drug use was described in different wards and age groups, and the proportion of different off-label used drugs was analyzed. Results The total 29 cross-sectional studies were included, involving 8 560 children and 41 655 prescriptions. a) Median (IQR) of off-label use incidence: Neonatal ICU 52.5% (23.0% to 44.8%), Pediatric ICU 43.5% (34.5% to 60%), General pediatric ward 35.5% (23.8% to 43.3%), Pediatric surgical ward 27.5% (23.0% to 44.8%); b) The results of off-label incidence in different age groups were inconsistent among different studies; and c) The off-label drug use for “no pediatric information” had the largest proportion, followed by dose and age. Conclusion a) Off-label drug use exists widely around the world, but the incidence varies a lot in different countries and different types of wards; b) The incidence of off-label drug use may be higher in ICU than in non-ICU, and higher in the neonatal ward than the pediatric ward; c) The off-label drug use for no pediatric information is the commonest type, and further clinical studies should focus on areas in which high quality evidence is totally absent; and d) The multi-center studies with unified design on off-label drug use in hospitalized children in China are urgently needed to provide evidence for policy-making.
Objective To evaluate the cost-effectiveness of chemotherapy in children with newly diagnosed Hodgkin lymphoma at low-, intermediate-, and high-risk. Methods From the perspective of health system, a decision-tree model was designed for cost-effectiveness analysis. The chemotherapy regimens of low-risk group included OEPA (vincristine, etoposide, prednisone, doxorubicin), AV-PC (doxorubicin, vincristine, prednisone, cyclophosphamide), and ABVD (doxorubicin, bleomycin, vincristine, dacarbazine); intermediate-risk group included OEPA, ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide) and ABVD; high-risk group included OEPA, ABVE-PC, ABVD and BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). The effectiveness and cost parameters were derived from the event-free survival rate reported in the literature, the drug linked reference price in Sichuan province, and treatment price of medical institutions. Univariate and probabilistic sensitivity analysis were performed to explore the impact of uncertainty. Results In the low-risk group, compared with AV-PC, the incremental cost-effectiveness ratios (ICER) of OEPA and ABVD were 80 700 yuan and 108 799 yuan, respectively. In the intermediate-risk group, compared with OEPA, the ICER of ABVE-PC and ABVD were −17 737 yuan and −4 701 yuan respectively. In the high-risk group, compared with ABVE-PC, the ICER of OEPA, ABVD and BEACOPP were 149 262, 472 090 and 64 652 yuan, respectively. Univariate sensitivity analysis showed that in low-risk group, the most influential factors were cost of OEPA and cost of ABVD; in moderate-risk group were cost of ABVE-PC and cost of OEPA; in the high-risk group were cost of OEPA, cost of ABVD, and cost of BEACOPP, respectively. The results of probabilistic sensitivity analysis are basically consistent with those of the main analysis. Conclusion If China's per capita gross domestic product in 2023 (89 358 yuan) was used as the willingness-to-pay (WTP) threshold, OEPA in the low-risk group, OEPA in the intermediate-risk group and BEACOPP in the high-risk group are cost-effective.
Objective To evaluate the related laws, regulations and guidelines about off-label drug use in several countries, so as to provide evidence for regulating off-label drug use in China. Methods The following 3 Chinese databases as CBM, CNKI and VIP, 11 foreign databases including EMbase, PubMed and so on, 15 countries’ official websites of pharmaceutical administration department or academic organization, and WHO website were searched to obtain the related laws, regulations and guidelines about off-label drug use. By adopting the system evaluation method and self-defined index evaluation, the quality of the included literatures was evaluated in three aspects: literatures’ type, content relevance and timeliness. Seven researchers independently extracted data by Excel which included basic information of literatures, preconditions of off-label drug use, medicines categories that could be off-labelly used, regulations and legal responsibility in off-label drug use. And finally the descriptive analysis was conducted. Results A total of 4 735 literatures were retrieved, 104 of which were finally included, including 89 at grade A quality level (85.58%) and 15 was at grade B (14.42%). The analysis showed that, a) Seven countries had laws related to off-label drug use: America, Germany, Italy, Netherland, New Zealand, India and Japan. Except India, the rational off-label drug use was allowed in the other 6 countries. The right to prescribe off-label drug was defined in Britain and Ireland; b) Medical staff had to take the responsibility of off-label drug use in the country where the duty regulations were formulated; and c) Ten countries published guidelines or statements related to off label drug use by their official departments and academic organizations. And the regulation included the following procedures: firstly, to obtain the relative information and evidence; secondly, to get the informed consent; thirdly, to be approved by the ethics committee and/or pharmacy administration committee; fourthly, to record the reasons and effectiveness of off-label use; fifthly, to monitor the adverse reactions of off-label drug use. Besides monitoring the medical institutes, the pharmaceutical companies had also be monitored which included the following 3 aspects: a) to require companies to train specialized staffs to answer the questions related to off-label drug use; b) to open the contact information of medical departments of companies; and c) to prohibit preaching and advertising the off-label drug use. Conclusion Off-label drug use has its rationality and necessity. To protect the safety of patients, avoid the risk for hospitals and medical staffs, it requires formulating relative regulations soon in order to manage the off-label drug use in China. As a developing country, China is different from the developed countries in health care system. Therefore, when formulating the regulations, it is necessary to perform evidence-based evaluation on each country’s laws, regulations and guidelines about off-label drug use, with Chinese national conditions and experts’ opinions in combination. After a regulation is preliminarily drawn up, it needs to be put into pilot practice, and then revised and spread to the whole country.
Objective To study medication usage in women and children from the distress area related to the Wenchuanearthquake. Methods Information about which medications that 329 patients used in West China Second University Hospital,Sichuan University was collected by the HIS system and classified by using the ICD-10system.The cases and times of medication, the total number of drugs, the drug cost per capita, and the drug cost per day were calculated using Excel. The defined daily dose (DDD) and drug utilization index (DUI) were analyzed. According to the principle of DDD amp; DUI, CDDD amp; CDUI were designed to analyze the drugs used by children. Results A total of 398 drugs in 25 categories were applied to 329 patients. Every case used infusion solutions, the DDDs of vitamins were the highest, the usage and duration of vitamins and antibacterial agents were the longest among the 25 kinds of the drugs. The cost of Amoxicillin Sulbactam injection was the highest. Many kinds of medications were prescribed to these patients,the rate of DUIgt;1 vs DUIlt;1 are 32.3% amp;47.2%. The results of CDUI indicated overuse of drugs was serious in children less 1yr old.The CDUI of precortisyl was the highest:40 to 80. Conclusions The system for distribution of medication to patients to children and women during an emergency is flawed. According to our findings we make new suggestions for changes, which have to be proved by further research.
ObjectivesTo construct a follow-up evaluation indicator system on the implementation of the WHO resolution of " Access to essential medicines” by systematic review, and to provide a methodological support for tracking the implementation of the resolution, with a view to providing evidence of decision-making to promote the accessibility of essential medicines and further promote and improve the national essential medicine policy. It also provides a methodological reference for investigating the implementation of other public health sector resolutions.MethodsPubMed, EMbase, The Cochrane Library, Web of Science, CBM, WanFang Data and CNKI databases and relevant international or national official websites of pharmaceutical administration department or academic organization were searched to collect studies on accessibility of WHO essential drugs from inception to February, 2016. Two researchers independently screened literature, extracted data, and qualitative analysis was used to sort out and screen the evaluation indicators for the implementation of the WHO resolution of "Access to essential medicines".ResultsA total of 60 relevant literatures, three guides and 19 progress reports of the World Health Assembly from official websites were included. Through the screening of indicators, we could get two parts: the indicators of measures to implement the resolution and the indicators of the results of the implementation of the resolution.ConclusionsThis study analyzes the implementation of the resolution of the health system in the progress report of the World Health Assembly 2013–2015, divides the implementation of the resolution into two parts: the implementation of the resolution and the results of the implementation of the resolution. An indicator system for establishing measures and evaluation the resolution has been found. Expert consultations will be further developed to establish the final indicators for the implementation of the "Access to essential medicines".