With the perspective of evidence-based medicine, this review aims to investigate the effectiveness and safety of off-label drug use of bevacizumab for eye disease, and explore the barriers to further study. And then, suggestions for the supported evidence and clinical use of off-label drug use will be provided based on this case.
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.
ObjectiveTo systematically review the global situation of off-label drug use in cancer patients. MethodsWe searched PubMed, EMbase, CNKI, CBM and VIP databases from their inception to October 2014, to collect studies on off-label drug use in cancer patients. The publication language was limited to English and Chinese. Combieg criteria was used for methodological quality assessment of included studies. A describe analysis was used to analyze the incidence and the proportion of different off-label used drugs. ResultsA total of 14 cross-sectional studies were included. Among them, 1 was from Switzerland, 1 was from Italy, 1 was from Australia, and the other 11 studies were from China. Seven included studies reported the investigated patients' number, containing 3 713 cancer patients and 13 238 prescriptions. The incidences of off-label drug were 2 844, accounting for 21.48%. There were similar rates of off-label prescriptions in Europe, Asia and Australia, but the average off-label prescriptions of European cancer patients were lower than Asia and Australia. The total rate of "unapproved dose", "unapproved indication", and "unapproved solvents" were more than 80% in off-label drug use. ConclusionThe average off-label prescriptions of European cancer patients are lower than Asian and Australian. "Unapproved dose", "unapproved indication" and "unapproved solvents" are the most common off-label prescription in off-label drug use.
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.
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.
ObjectiveTo investigate the situation of off-label drug use in dose (OLDUD) of ambroxol hydrochloride injection (AHI) in perioperative period among patients for stanford type A aortic dissection in Guangdong General Hospital, so as to provide references for the rational application of AHI in clinical practice. MethodsAll medical orders of AHI for patients had aortic arch replacement for Stanford type A aortic dissection in Guangdong General Hospital between January 2005 and December 2014 were included. The patients were divided into a mild OLDUD ( < 450 mg) group, a moderate OLDUD (450 mg≤OLDUD < 900 mg) group, and a high OLDUD (≥900 mg)group. The preoperative and postoperative features, incidence of PPCs, mortality, incidence of reintubation, time of mechanical ventilation, time stay in ICU, time stay in hospital and the overall costs among three groups were compared by SPSS 22.0 software. Resultsa) A total of 549 patients were included. The incidence of OLDUD was 99.82%. The most common PMDDs were 450 mg (n=358) and 900 mg (n=88). b) The three groups were well matched for perioperative and operative variables. c) The incidence of preoperative drug use was 8.6%. The incidences (5.5% vs. 7.7% vs. 15.7%, P=0.022) and maximum doses (180 mg vs. 300 mg vs. 450 mg, P=0.014) of preoperative drug use were statistically different in mild OLDUD, moderate OLDUD and high OLDUD groups. The days of preoperative drug use were not different (3 d vs. 2.5 d vs. 2 d, P=0.307). The days of postoperative drug use (9.5 d vs. 13 d vs. 19 d, P < 0.001) and postoperative drug use in maximum doses (7 d vs. 8 d vs. 7 d, P=0.005) were different. d) The incidence of PPCs was 100%, and the mortality (8.2% vs. 6.6% vs. 9.0%, P=0.696) was not statistically different among mild OLDUD, moderate OLDUD and high OLDUD groups. However the incidence of reintubation (14.3% vs. 13.8% vs. 27%, P=0.009), time of mechanical ventilation (37 h vs. 50 h vs. 114 h, P < 0.001), time stay in ICU (138 h vs. 178.5 h vs. 316 h, P < 0.001), time stay in hospital (25 d vs. 27 d vs. 34 d, P=0.001) and the overall costs (¥ 0.17 million vs. ¥ 0.19 million vs. ¥ 0.25 million, P < 0.001) were different among three groups. Moreover, they were all increasing along with the dose of AHI. ConclusionAHI cannot improve the prognosis of patients having aortic arch replacement for Stanford Type A Aortic Dissection in a dose-dependent manner. Further well-designed prospective studies should be conducted to verification or falsification.
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 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.
ObjectiveBased on the off-label drug use (OLDU) record application of Alprostadil injection (LipoPGE1) which was the only one rejected in the Guangdong General Hospital in 2013, the interventional measures were carried out to reduce unreasonable off-label drug use of Lipo-PGE1. MethodsMedical orders about OLDU in dosage of Lipo-PGE1 were intervened in through education, communication and monitoring. The situation of drug use was summarized in all departments after intervention through exporting all the medical orders about inpatients' use of LipoPGE1 during hospitalization in August, 2013 to July, 2014 and OLDU incidence in dosage, prescribed daily dose (PDD) and drug use density (DUD) in each department were calculated. The interventional effect was analyzed by comparing with the baseline data. Resultsa) A total of 78 044 medical orders involving 6 426 case-times were analyzed. According to the data of cases, medical orders and drug use amount, the OLDU incidences were 8.68%, 5.87% and 10.53%, respectively, compared with 34.43%, 25.16% and 41.37% before intervention had declined significantly (P < 0.05). OLDU occurred in 69.44% departments (25/36) before intervention and declined to 55.56% (20/36) after intervention. b) OLDU incidences of 22 departments were declined after intervention. There were 2 departments with the OLDU incidence in dose > 20%: ICU (39.68%) and cardiac surgery (32.78%). c) After the intervention, the PDD of the whole hospital fell to 10.52μg from 12.77μg and DUD fell to 8.87 from 15.12. There were 20 departments whose PDDs were off-label and 3 departments whose PDDs were above the average level of the whole hospital after the intervention. The three departments were ICU (13.61μg), cardiac surgery (12.68μg) and rheumatology (11.26μg). ConclusionExtensive publicity and education, targeted communication and regular monitoring and feedback are effective measures to intervene in unreasonable OLDU. After intervention, the phenomenon of off-label drug use of Lipo-PGE1 is improved significantly. This study provides a workable avenue to manage off-label drug use in hospital.
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.