Individual patient data meta-analyses are conducted through development of collaboration with trial investigators, central collection and checking of individual patient data of all eligible trials, and pooling of patient data to produce the best estimate of effects of health care interventions. They ensure study data to be update, accessible, reliable and complete so as to minimize the risk of bias, and are the gold standard of systematic reviews addressing effects of health care interventions. Meta-analyses using individual patient data enable higher flexibility of data analyses and more completeness and balance of results interpretation. The study conduct differs between individual patient data versus conventional meta-analyses. This article discussed the steps of conducting individual patient data meta-analyses.
Objective To analyze the withdrawal reason of natalizumab in depth based on the serious adverse reaction reports and approval channel, and to provide decision references for more safe and effective report method of other biologicals. Methods We searched MEDLINE, EMbase, and the official websites of Food and Drug Administration (FDA) for case reports, approval channel, and the relevant information of drug marketing or withdrawal. Results Four case reports and fourteen official reports were included. Three cases of progressive multifocal leukoencephalopathy (PML) were reported in the clinical trials after natalizumab’s initially approval with two dead and one disabled, which could be retrieved by hemodialysis (2 cases hitherto). Consequently, multiple sclerosis (MS) patients were willing to bear the risk. Two cases of natalizumab-related PML (0.06‰) were confirmed in 32 000 patients without death report after two years of its remarketing, in July 2008. Another PML patient was reported in October 2008. Because of its non-substitutability for treating MS and Crohn disease (CD), FDA announced that patients could still use natalizumab under the close monitoring. Conclusion (1) The most serious adverse reaction of treating MS and CD with natalizumab is PML, but it can be preventable and curable now. The monitoring findings of efficacy and adverse reaction during the postmarketing indicate that the review system is perfect and practicable relatively, and can give references for other high-risk drugs on the fast or standard approval channel, for example, Chinese medicine injection can draw lessons from it. (2) The remarketing of natalizumab not only provide significant risk management precedent for other drug-development firms, but also brings hope to the remarketing or relaunching clinical trials for the suspected sideeffect drugs. (3) Because of the fast-track reviewing of natalizumab and the overlap between the research of Good Clinical Practice (GCP) and the post-marketing evaluation, we should continue to track the information and provide new evidence.
Based on the principles and methods of systematic review of randomized controlled clinical trials, systematic review of economic analyses can integrate information from multiple economic studies which focus on the same clinical questions. It can also provide important insights by systematically examining how differences among studies lead to different results. Generally, there are seven steps to conduct such a review: 1) formulating questions; 2) establishing eligibility criteria; 3) searching and selecting eligible economic analyses; 4) assessing the validity of economic analyses; 5) acquiring data; 6) analyzing and synthesizing data; and 7) presenting results. Owing to the specificity of economic analyses, many methodological challenges exist, including the varieties of economic models, analytic perspectives, time horizons, and uncertainty and sensitivity analysis among different economic analyses. This may cause difficulties for critical assessment of the economic analyses.
Economic evaluation used alongside clinical trials has become a hot spot in the development of clinical studies. The definition and classification of the cost were introduced in this article. The ways to conduct cost analysis in clinical trials were introduced systematically, including the identification, collection and analysis of the data of costs, and the concern of the analysis.
In recent years, an increasing amount of systematic reviews have been published; however, few reviews adequately considered and reported details of interventions, which not only limited the usability of systematic reviews but also wasted resource. In order to improve reporting of intervention details in systematic reviews, BMJ recently published recommendations. This paper interprets the recommendations to improve usability of systematic reviews.
Evidence-based Chinese medicine (EBCM) is one of the innovative achievements in the development of evidence-based medicine (EBM) in China. The EBCM has made initial progress: the evidence-based scientific decision-making model has become popular; a series of key technologies for evidence-based evaluation and research of traditional Chinese medicine (TCM) have been established; several technical specifications have been formulated in line with international standards; clinical evidence database of TCM has been established; a number of high quality clinical trials have been published in internationally renowned journals; and the International Forum on Evidence based Chinese Medicine(EBCM) has become a brand conference. Difficulties in EBCM development mainly involve: lack of high quality clinical evidence, difficulty in producing evidence, and decentralization of research team. Based on opportunities and challenges of the development of TCM, this article proposed the short-term and long-term goals, implementation paths and five key directions for the development of EBCM in the future, and puts forward three suggestions for further development of EBCM.
In the study of real-world data, the pragmatic randomized controlled trial can provide the optimal evidence for clinical decisions. Although randomization protects against confounding, post-randomization confounding may still arise due to non-compliance. Traditional intention-to-treat analysis will drift apart from true estimation and lead to deviation of clinical decisions. Meanwhile, the alternative traditional methods would subject to bias and confounding. Thus, new methods are required for revolution, i.e., instrument variable method and modern per-protocol analysis. Our study reviews the defects of traditional methods in pragmatic randomized controlled trials, and then refers to two new methods with a detailed discussion of strengths and weaknesses. We aim to provide researches with insights on choosing the statistical methods for pragmatic trial.
Evidence-based medicine is the methodology of modern clinical research and plays an important role in guiding clinical practice. It has become an integral part of medical education. In the digital age, evidence-based medicine has evolved to incorporate innovative research models that utilize multimodal clinical big data and artificial intelligence methods. These advancements aim to address the challenges posed by diverse research questions, data methods, and evidence sources. However, the current teaching content in medical schools often fails to keep pace with the rapidly evolving disciplines, impeding students' comprehensive understanding of the discipline's knowledge system, cutting-edge theories, and development directions. In this regard, this article takes the opportunity of graduate curriculum reform to incorporate real-world data research, artificial intelligence, and bioinformatics into the existing evidence-based medicine curriculum, and explores the reform of evidence-based medicine teaching in the information age. The aim is to enable students to truly understand the role and value of evidence-based medicine in the development of medicine, while possessing a solid theoretical foundation, a broad international perspective, and a keen research sense, in order to cultivate talents for the development of the evidence-based medicine discipline.
Objective To assess the rationale for including rifampicin150/isoniazid75/ethambuto/275mg fixed dose, combination oral tablets/3-FDC R150H75E275/ in the WHO Model List of Essential Medicines (WHO EML) for treatment of category II tuberculosis (TB II) and to provide evidence for the updating of national guidelines. Methods We searched Chinese Biomedical Database (CBM, 1978 to 2006), The Cochrane Library, Issue 4, 2006, the Database of Abstracts of Reviews of Effects (1994 to 2006, the Centre for Reviews and Dissemination website), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), BIOSIS Previews (1997 to 2006), websites for grey literature and the references of studies. We applied inclusion and exclusion criteria in assessing the studies we found and eligible studies were graded following an assessment of their quality. Results Thirty-six randomized controlled trials, 4 controlled clinical trials, 11 descriptive studies and 5 WHO/national guidelines were included. Rifampicin (R), isoniazid (H) and ethambutol (E) were used in the ccontinuation phase (CP) of TB II in guidelines of WHO and high tuberculosis (TB) burden countries, but the course of treatment and dosage regimens varied. R, H and E were also widely used in conditions of pulmonary tuberculosis (PTB), extrapulmonary tuberculosis (EPTB) and pulmonary diseases caused by nontuberculous mycobacteria (NTM).Conclusions It is recommended that FDC RHE be included in WHO EML for the treatment of TB II.The suggested dosage ratio of RHE is 1:1:2, which needs to be adjusted based on more solid clinical evidence. High quality clinical studies and systematic reviews on the effectiveness, safety, economics and applicability of WHO and national guidelines and their outcomes in high TB burden countries are needed to guide their updating, promote rational resource allocation and improve cost effectiveness. Alternative drugs or drug combinations with good profile of effectiveness, safety, economics, and applicability for the prevention and treatment of drug-resistant tuberculosis are also needed to be developed.