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.
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 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.
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.
ObjectiveThis study proposes employing large language models (LLMs) for medical literature quality assessment, exploring their potential to establish a standardized and scalable intelligent evaluation framework for off-label drug use (OLDU). MethodsThe study used two freely available LLMs platforms in China, DeepSeek-R1 and Doubao. Following the medical literature quality assessment tools recommended in the evidence-based evaluation specification for OLDU issued by the Guangdong Pharmaceutical Association, we selected the Jadad scale and the MINORS criteria. These tools were employed to assess the quality of the two most prevalent types of medical literature in OLDU evidence evaluation: randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs). Utilizing chain-of-thought (CoT) prompting techniques, we developed standardized evaluation templates. The quality scores generated by the LLMs were then compared against those reported in systematic reviews or assigned by clinical pharmacists. ResultsFor RCT, DeepSeek-R1 demonstrated consistency with human assessments in quality appraisal. However, discrepancies exist between the Doubao model and manual evaluation results, with three repeated evaluations yielding inconsistent outcomes and inaccurate identification of "allocation concealment" items. For non-RCT, all models achieved concordant quality assessment outcomes with human evaluators, while demonstrating unique capacity to detect systematic evaluation inaccuracies attributable to human subjective bias. ConclusionThis study demonstrates that prompt engineering-driven LLMs can efficiently conduct quality assessments of medical literature. However, the selection of models requires rigorous validation against domain-specific benchmarks, alongside mandatory expert validation of scoring outputs. Our findings further reveal the necessity of refining current quality appraisal criteria through granular operational definitions, thereby facilitating standardized automation. This approach not only enhances the efficiency and transparency of evidence-based decision-making for OLDU but also extends to systematic reviews and rapid health technology assessments. By replacing traditional literature quality evaluation models with automated scoring mechanisms, it enables a paradigm shift in the efficiency of evidence processing.
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.
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 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.
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.