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 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.
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.
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.
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 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 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.
With the real-world study (RWS) becoming a hotspot for clinical research, health data collected from routine clinical practice have gained increasing attention worldwide, particularly the data related to the off-label use of drugs, which have been at the forefront of clinical research in recent years. The guidance from the National Medical Products Administration has proposed that real-world evidence (RWE) can be an important consideration in supporting label expansions where randomized controlled trials are unfeasible. Nevertheless, how to use the RWE to support the approval of new or expanded indications remains unclear. This study aims to explore the structured process for the use of RWE in supporting label expansions of approved drugs, and to discuss the key considerations in such process by reviewing the documents from relevant regulatory agencies and publications from public databases, which can inform future directions for studies in this area.
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.