Objective To introduce the evidence-based evaluation on off-label uses at home and abroad, so as to investigate a systematic method of evidence-based evaluation on off-label uses. Methods In combination with the domestic and international research literature, a systematic method of evidence-based evaluation on off-label uses was discussed from the following three aspects: sources of evidence, levels of evidence, and recommendation strength. Results Sources of evidence included Clinical Pharmacology, DRUGDEX? System, NCCN Drugs amp; Biologics Compendium and handsearched literature. Levels of evidence and recommendation strength could refer to the 2009 grade system of Oxford Centre for Evidence-Based Medicine, and the strength of recommendations and scientific support of DRUGDEX? System. Conclusion A systematic method of evidence-based evaluation on off-label uses is initially established.
Objective To determine the extent of off-label drug use in Pediatric Wards of West China Second University Hospital in 2010 and analyze its risk factors, so as to provide baseline data for getting acquainted with the extent of off-label drug use in pediatrics in China, and for making policies of off-label drug use. Methods The proportionate stratified random sampling was conducted to select medical advice and discharge medication for hospitalized children in Pediatric Wards in 2010. According to drug instructions, the off-label drug use of prescriptions of all selected children was analyzed in the following aspects, the category of off-label drug use, age, category of drugs and wards. In addition, a logistic regression was done that modeled the odds of receiving an off-label prescription as a function of the following possible risk factors: age, sex and the rank of doctors. Results The total 749 children were selected, and 14 374 prescriptions involving 385 drugs were analyzed. The rate of off-label drug use was 98.00%, 78.96% and 88.05% in children, prescriptions and drug categories, respectively. The main categories of off-label drug use were no pediatric information (29.41%), indication (18.35%), dosage (17.61%) and dosage range (±20%) (13.52%). The top 2 age groups of off-label drug use were adolescents (83.56%) and children (80.58%). The top 4 drugs of off-label use were those for alimentary tract and metabolism (82.28%), anti-infectives for systemic use (75.06%), blood and blood forming organs (79.27%) and respiratory (58.27%). The top 2 wards of off-label drug use were Pediatric Hematology (88.27%) and Neonates (79.12%). In hospital, children, adolescents and male patients had higher risk factors of off-label drug use, and doctors with senior rank prescribed more off-label prescriptions than those with intermediate rank. Conclusion The off-label drug use in Pediatric Wards is common in West China Second University Hospital. On the one hand, drug instructions lack the pediatric information, and, on the other hand, it’s badly in need of developing relevant legislations, regulations or guidelines to regulate off-label drug use, in order to avoid doctor’s professional risks and ensure the safety of pediatric drug use.
Objective To determine the extent of off-label drug use in pediatric outpatients of West China Second University Hospital in 2010, and to analyze its possible risk factors, so as to provide baseline data for getting acquainted with the extent of off-label drug use in pediatrics in China and developing policy of off-label drug use. Methods The stratified random sampling was conducted to select prescriptions of children aged 0 to 18 years in pediatric outpatients of the West China Second University Hospital in 2010. According to drug instructions, off-label drug use of prescriptions of all selected children was analyzed in the following aspects, the category of off-label drug use, age, category of drugs. In addition, an analysis was conducted to check the relationship between off-label use and following possible risk factors: age, sex, essential medicines and over-the-counter drugs. Results A total of 2 640 prescriptions with 8 588 medical advices involving 329 drugs were extracted and analyzed, with incidence rates of off-label drug use accounting for 76.59%, 40.88% and 83.89%, respectively. The main categories of off-label drug use were no pediatric information (35.57%), indication (25.44%), and dosage (25.31%). The top 2 age groups with highest incidence rate of off-label drug were neonates (54.35%) and adolescents (49.64%). The top 4 drugs with highest incidence rate of off-label drug were respiratory system medicines (48.12%), Chinese patent medicines (48.12%), digestive and metabolic system medicines (33.36%), and systemic anti-infectives (16.27%). The off-label use risks in all age groups in the hospital were indifferent, and the essential medicines and prescription medicines were likely to present higher risks of drug off-label. Conclusion Off-label drug use in pediatric outpatients is common with growth trend in pediatric outpatients of the West China Second University Hospital. On the one hand, drug instructions lack pediatric information, and on the other hand, it’s badly in need of developing relevant legislation, regulations or guidelines to regulate off-label drug use, providing more evidence by conducting clinical trials on pediatric drugs, encouraging the development and production of the applicable drugs and dosage forms for children, and establishing the children essential medicine list, so as to avoid doctor’s professional risk and ensure the safety of pediatric drug use.
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 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 investigate the off-label prescriptions in pediatrics in West China Second University Hospital and to analyze the reasons and performance, so as to provide the baseline data for improving the rationality drug use in pediatrics in China. Methods The prescriptions of pediatrics outpatient department were randomly selected from May 2008 to April 2009; and the off-label use was analyzed according to the package inserts in the following aspects, the types of off-label use, the rate of off-label use in different age groups and categories of medicine. Results Of the total 2 400 prescriptions, 1 398 (58.25%) involving off-label use. All sample prescriptions contained 6028 records, 1 923 (31.90%) involving off-label use. The problems such as dosage (45.98%), frequency (21.17%) and age (18.19%) were the top-three types of off-label use. The rate in different age groups ranked as the top-three were school-age (61.56%), followed by preschool (60.77%) and infants (57.56). The top-five categories of medicines in off-label use were anti-allergy drugs (49.45%), digestive system drugs (49.32%), externally applied drugs (41.49%), Chinese patent drugs (34.60%) and nervous system drugs (33.78%). Conclusion The off-label drug use is widespread in pediatrics outpatient department. It is an effective approach to reduce off-label use and improve drug safety through strictly abiding by the instruction of usage and dosage as well as selecting a suitable dosage form.
ObjectiveTo retrospectively analyze off-label drug use (OLDU) situation of ambroxol hydrochloride injection (AHI) among inpatients in the Guangdong General Hospital in 2012, so as to provide references for AHI OLDU. MethodsAll medical orders of AHI for inpatients in the Guangdong General Hospital in 2012 were included, and OLDU was judged according to drug labels. We summarized situation of drug use in all departments, analyzed OLDU incidence in administration path and in dose, calculated prescribed daily dose (PDD) and utilization index (DUI) in each department to evaluate the degree of OLDU in dose. Resultsa) A total of inpatients 138 227 patient-days who used AHI were included. OLDU occurred in all departments in this hospital and the total OLDU incidence was 67.06%. b) OLDU in dose occurred in 71.43% of the departments (25/35) with an incidence of 29.53%; the top 4 departments were cardiac surgery intensive care unit department (CICU) (97.74%), cardiac surgery department (97.51%), pediatric cardiac surgery department (72.30%) and pediatric intensive care unit department (PICU) (70.28%) in order. c) The PDDs in CICU department, cardiac surgery department, PICU departments, pediatric cardiac surgery department, oncological surgery ward, neurosurgery ward and intensive care unit (ICU) were higher than the defined daily dose (DDD), of which, the DUI/cDUI in CICU, cardiac surgery department, PICU and pediatric cardiac surgery department were 1 to 3 times higher than normal level. d) No relevant adverse drug reaction/adverse event (ADR/AE) reports were received in this hospital in 2012. ConclusionAHI is widely used in the Guangdong General Hospital, and AHI OLDU is commonly-seen. Further studies should be conducted to analyze the influence factors of AHI OLDU in dose and to evaluate the rationality of its application.
A study on clinical management methods and process of off-label drug use (OLDU) is carried out at managerial level in the Guangdong General Hospital to develop management regulations, processes and strategies of OLDU, so as to regulate OLDU behaviour in clinic. The hospital officially initiated the application-recording-approval process of OLDU in February, 2013, receiving 22 OLDU applications from 5 clinical departments in the first batch. The pharmacy management and pharmacotherapeutics committee approved eight applications and rejected one application according to regulation procedures. In this way, the Guangdong General Hospital well regulate the OLDU behaviour of physicians, which is significant to the further studies in OLDU in this hospital.
ObjectiveBased on the off-label drug use (OLDU) record application of alprostadil injection (Lipo-PGE1) which was the only one rejected in the Guangdong General Hospital in 2013, we retrospectively investigated all the background information of inpatients' OLDU of Lipo-PGE1 in 2012, so as to provide references for intervention of OLDU and effect evaluation. MethodsAccording to OLDU in dose record application of clinical departments, we summarized medical orders about inpatients' use of Lipo-PGE1 during hospitalization in 2012 and analyzed OLDU situation according to drug labels. Then, we summarized situation of drug use in all departments, analyzed OLDU incidence in dose, calculated prescribed daily dose (PDD) and drug use density (DUD) in each department to evaluate the degree of OLDU in dose. Resultsa) A total of 106 576 medical orders involving 8 620 case-times were analyzed. According to the data of cases, medical orders and drug use amount, the OLDU incidences were 34.43%, 25.16% and 41.37%, respectively. Lipo-PGE1 was used in every clinical department in this hospital and OLDU occurred in 69.44% departments (25/36). b) According to the number of medical orders, there were 6 departments with the OLDU incidence in dose > 50% and 5 departments with the OLDU incidence in dose during 50% to 20%. c) The average of PDD of the whole hospital was 12.77 μg. A total of 25 departments' PDDs were off-label, and 10 departments' PDDs were above the average level of the whole hospital. The ICU's PDD was the highest, with 2.35 times more than label dose. d) The PDD in each department was not directly proportional to DUD, which indicated the degree of OLDU in dose was not directly proportional to use intensity. This may be caused by different disease burdens in departments. ConclusionLipo-PGE1 is widely used in the Guangdong General Hospital where OLDU in dose occurs commonly. Since PDD and DUD reflect different contents, the two indicators should be combined to monitor OLDU.
ObjectiveTo understand the situation of off-label use of aspirin among outpatients in Sun Yatsen Memorial Hospital, so as to provide baseline data for developing off-label drug use policy. MethodsA stratified random sampling method was used to collected prescription data of aspirin among outpatients in 2013. The incidence rates between different types of off-label use of aspirin were determined by chi-square test, and the influence factors of off-label drug use were analyzed by logistic regression model. ResultsA total of 5 023 prescriptions with aspirin were collected and analyzed, with incidence rate of off-label use up to 17.7%. The major category of off-label use was no indication (94.38%). The top 3 no indications were recurrent abortion, infertility and systemic lupus erythematosus. Drug specification, gender, age and prescribed department were the risk factors of off-label use. ConclusionAspirin off-label use is common among outpatients in Sun Yat-sen Memorial Hospital in 2013, especially in obstetrics and gynecology department and assisted reproductive center. The results suggest that more clinical studies about aspirin for reproduction are needed to provide more evidence of drug use, so as to ensure the safety of drug use in special populations and avoid potential medical risk.