Off-label Drug Use Research Articles

Physicians' reasons not to discontinue long-term used off-label antipsychotic drugs in people with intellectual disability.

People with intellectual disability (ID) frequently use antipsychotic drugs on an off-label base, often for many years. Physicians' decisions to discontinue these drugs not only depend on patient characteristics, like the presence of mental or behavioural disorders, but also on environmental factors, such as inappropriate living circumstances, and on attitudes, knowledge and beliefs of staff, clients and their representatives towards the effects of antipsychotic drug use. In this study, we therefore investigated the influence of participant and setting-related factors on decisions of physicians not to discontinue off-label prescribed antipsychotics. The study took place in living facilities of six service providers for people with ID spread over the Netherlands and staffed with support professionals, nurses, behavioural scientist and physicians and was part of an antipsychotics discontinuation trial. ID physicians had to decide whether the off-label use of antipsychotics could be discontinued. Medical and pharmaceutical records were used to establish the prevalence of antipsychotic drug use in the study population, along with duration of use and whether the use was off-label. Reasons of physicians not to discontinue the prescription of antipsychotics in those participants who used off-label antipsychotics for more than a year were collected and categorised as related to participant or setting characteristics, including lack of consent to discontinue, and staff members, participants or their legal representatives. Of the 3299 clients of the service providers, 977 used one or more antipsychotic drugs. The prevalence of antipsychotic drug use was 30%. Reasons for use were in 5% of cases, a chronic psychotic disorder classified according to Diagnostic System Mental Disorders, Fourth Edition, criteria, in 25%, present or past (suspected) non-schizophrenia-related psychotic symptoms and in 69%, challenging behaviours. Overall, physicians were willing to discontinue their prescriptions in 51% of cases, varying from 22% to 87% per service provider. The odds for decisions of physicians to discontinue off-label prescriptions varied from 0.19 to 13.95 per service provider. The variables 'a living situation with care and support' and 'challenging behaviour' were associated with a higher chance of discontinuation. The main reasons for decisions not to discontinue were concerns for symptoms of restlessness, the presence of an autism spectrum disorder, previously unsuccessful attempts to discontinue and objections against discontinuation of legal representatives. Reasons for physicians' decisions not to discontinue the off-label use of antipsychotics varied largely between the service providers. The prevalence of antipsychotic drug use for off-label indications in people with ID remains high. The results of this study indicate that there is a large variation in clinical practice of physicians regarding discontinuation of long-term antipsychotic drug prescriptions, which may be partially related to environmental factors as setting culture and attitudes of staff towards off-label antipsychotic drug use in persons with ID.

Rituximab for the treatment of poly- and dermatomyositis : Results from the GRAID-2 registry

In the treatment of poly- and dermatomyositis, only alimited number of treatment modalities are established. The goal of the GRAID-2 registry was to study off-label use of biologic drugs for this indication in Germany. Analysis of the data of the GRAID-2 registry for poly- and dermatomyositis. In 22of the 23patients in the GRAID-2 registry, rituximab (RIX) was administered, while 1patient was given tocilizumab as off-label therapy. The 22patients who received RIX treatment were analyzed. At the start of treatment, the following active manifestations were present: myositis (n= 18), lung involvement (mainly interstitial lung disease; n= 10), arthritis (n= 10), skin manifestation (n= 9), and Raynaud syndrome (n= 5). Nine of the patients were Jo-1-antibody positive. All patients had previous treatments with multiple conventional immunosuppressive drugs. Treatment with RIX was given as infusions of 1 g i. v., which were repeated after 2weeks. Patients received amean of 3.09± 2.27 infusions (equivalent to 1.5cycles of 2× 1 g, max. 5cycles). Tolerability of RIX treatment was rated as very good in 16of 22patients (72%), good in 5(23%), and moderate in 1(5%). In all, 27adverse events were documented, with the majority being infections, whereby 2severe infections occurred (6.59 per 100 patient-years). Eighty six percent of the patients showed complete remission of their myositis and 79% of their arthritis. The mean value of creatinine kinase in plasma fell from 1505± 2534 U/l before the start of treatment to 39± 134 U/l at the last visit. Regarding lung involvement, 1of10 of the patients showed complete and 6of10 partial remissions. In 2of 10patients, lung disease was stable during treatment. RIX is the preferred off-label biologic drug for poly- and dermatomyositis in Germany. In spite of astrongly pretreated group of patients, the tolerability is acceptable, although the patient number in this investigation is small. Moreover, the results lead to the assumption that the majority of the patients had agood or even very good therapeutic response to RIX.

Inflammatory Bowel Disease in Childhood and Adolescence.

The incidence of inflammatory bowel disease (IBD) in childhood and adolescence is 5-11 cases per 100 000 persons per year, corresponding to a new diagnosis of IBD in 800-1470 patients in Germany each year. This review is based on pertinent publications retrieved by a selective search in PubMed, including guidelines from Germany and abroad. Children and adolescents with IBD often have extensive involvement and an aggressive course of disease. Nonetheless, infliximab and adalimumab are the only biological agents that have been approved for this group of patients. In Crohn's disease, exclusive enteral nutrition is the treatment of first choice for inducing a remission. Patients with (peri-)anal fistulae are treated primarily with infliximab. Corticosteroids and aminosalicylates should be used with caution. In contrast, children and adolescents with ulcerative colitis are treated with either aminosalicylates or prednisolone to induce a remission. As a rule, maintenance pharmacotherapy with thiopurines in Crohn's disease and severe ulcerative colitis, or with aminosalicylates in mild to moderate ulcerative colitis, is indicated for several years, at least until the end of puberty. Patients with refractory disease courses are treated with methylprednisolone, anti-TNF-α-antibodies, and/or calcineurin inhibitors. The spectrum of surgical interventions is the same as for adults. Specific aspects of the treatment of children and adolescents with IBD include adverse drug effects, the areas of nutrition, growth, and development, and the structured transition to adult medicine. Children and adolescents with IBD or suspected IBD should be cared for by pediatric gastroenterologists in a center where such care is provided. Individualized treatment with multidisciplinary, family-oriented longterm care is particularly important. Drug trials in children and adolescents are needed so that the off-label use of drugs to patients in this age group can be reduced.

Research on Approaches for Regulation of the “Off-label” use of Medicinal Products in the European Union

Abstract Despite the increasingly strict legislation on medicinal products, the „off-label use“ or „use of medicinal product outside the approved summary of product characteristics (SmPC)“ is a weak point of today’s drug regulation and raises many questions about the risk, ethics, and legality of this type of practice. In recent years, through guidance and legal changes in some countries were defined the conditions and responsibilities, but in the most European countries still lack rules for off-label prescribing. The purpose of this study was to identify and analyse different approaches to regulation, adopted by some member states as well as to summarize the efforts in demand of common harmonized approach to solve this problem within the European Union. In the study, we used the available regulatory information in different electronic resources associated with the off-label drug use in selected European countries without limited time range. The results show that decisions taken to regulate the issue have significant differences and specific approach, while none of them is enough satisfactory and comprehensive. In conclusion, it can be claimed that the existing regulatory rules in various countries require significant improvement and update.

Accuracy of tablet splitting and liquid measurements: an examination of who, what and how.

To examine factors that might affect the ability of patients to accurately halve tablets or measure a 5-ml liquid dose. Eighty-eight participants split four different placebo tablets by hand and using a tablet splitter, while 85 participants measured 5 ml of water, 0.5% methylcellulose (MC) and 1% MC using a syringe and dosing cup. Accuracy of manipulation was determined by mass measurements. The general population was less able than pharmacy students to break tablets into equal parts, although age, gender and prior experience were insignificant factors. Greater accuracy of tablet halving was observed with tablet splitter, with scored tablets split more equally than unscored tablets. Tablet size did not affect the accuracy of splitting. However, >25% of small scored tablets failed to be split by hand, and 41% of large unscored tablets were split into >2 portions in the tablet splitter. In liquid measurement, the syringe provided more accurate volume measurements than the dosing cup, with higher accuracy observed for the more viscous MC solutions than water. Formulation characteristics and manipulation technique have greater influences on the accuracy of medication modification and should be considered in off-label drug use in vulnerable populations.

Perception of oncology practitioners towards off-label use of anticancer medicines in Singapore

Objectives Prescribing drugs outside regulatory recommendation is known as off-label use. Studies have reported widespread off-label drug use in oncology practice. But the clinical, economic and humanistic outcomes for such practice are often uncertain. Hence, it is important to gather oncology practitioners’ perspective for the creation of clinical practice framework and policies. The aim of the study was to evaluate perception of oncology practitioners on off-label use in cancer therapy. Methods This study employed a cross-sectional design implemented in the form of the self-administered questionnaire at National Cancer Centre Singapore where more than 50% cancer patients of the country are treated. Key findings Eighty-one practitioners involving nurses (38%), medical oncologist (37%) and pharmacists (25%) were surveyed. The majority of practitioners (57%) agreed off-label use as indispensable practice in cancer therapy. Main reasons cited include advanced cancers where standard lines of treatment are exhausted (58%), lack of alternative approved drug (43%) and rare tumours (47%). Compared with other practitioners, medical oncologists viewed Phase 2 (73% versus 31%, P = 0.001) and conference abstracts (56% versus 23%, P = 0.003) as reasonable evidence for off-label use. Major concerns included lack of efficacy (58%), patient understanding (47%), uncertain safety (43%) and out-of-pocket cost (41%) associated with off-label use. Most viewed need for obtaining informed consent (86%) and institutional guidance (75%) as important elements in practice framework. Conclusion The study provides insights about off-label drug use practice and establishes the need for robust clinical guidance and educational strategies for oncology practitioners.

Status and analysis of off-label drug use in department of ophthalmology

Objective: To investigate and analyze the status of off-label drug use in department of ophthalmology of Beijing Tongren Hospital. Methods: Cross-sectional study. Prescription evaluation, off-label drug use application and temporary medicine purchase application were collected from January 2013 to March 2015. The off-label use of medication in department of ophthalmology were filtered out and analyzed according to the category of medications, the category of the off-label use of medication and the strength of evidence for the off-label use of medication. Results: Thirty-seven items of off-label uses of medication were included in this study. The off-label use of medication focused on the indications (19 items, 51.4%) and route of administration (18 items, 48.6%) in this study. Nineteen category of medication were involved, which accounted for 1.3% (19/1 462) drugs in the hospital formulary.The top 2 category of medication were adrenocorticoid drugs (21.1%, 4/19) and antitumor drugs (21.1%, 4/19). There are evidence to support 37 items of off-label drug uses. 5 items (13.5%) of off-label drug uses were labeled uses approved by Food and Drug Administration. One item (2.7%) of off-label drug use was in accord with international guidelines. Twenty items (54.1%) of off-label drug uses were in accord with expert consensus. Eight off-labels were evaluated by Micromedex, while the other 78.4% (29 items) were not evaluated by Micromedex. Conclusions: The off-label use of medications exists widely in department of ophthalmology, having its necessity and rationality. But we should pay attention to its standard management. (Chin J Ophthalmol, 2017, 53: 300-304).

Administration of Inhaled Pulmonary Vasodilators to the Mechanically Ventilated Neonatal Patient.

Pulmonary hypertension is a life-threatening condition that affects people of all ages that can occur as an idiopathic disorder at birth or as part of a variety of cardiovascular and infectious disorders. It is commonly treated with inhaled pulmonary vasodilators such as nitric oxide and less frequently using formulations and analogs of prostacyclin. To minimize systemic effects and preserve pulmonary vasodilation, vasodilators are often administered directly into the airway. Nitric oxide is the only USA Food and Drug Administration-approved inhaled pulmonary vasodilator that can be used during mechanical ventilation. Over the past two decades, interest has grown in the use of aerosolized prostacyclin and prostacyclin analogs for the treatment of pulmonary hypertension during mechanical ventilation. Clinicians who administer inhaled prostacyclin may not have a clear understanding of its risks because of the lack of data from large clinical trials examining safety and efficacy; moreover, its safe use remains poorly documented. The off-label use of drugs is legitimate, but prescribers must recognize the potential complications and liability in doing so. This manuscript aims to address potential problems related to the aerosol administration of pulmonary vasodilators in the mechanically ventilated neonatal patient.

Translational obstacles with off-label drug use in acute traumatic brain injury

Traumatic brain injury results in significant morbidity and mortality, and there is an urgent need for neuroprotective medications that can prevent the persisting symptoms and disabilities following injury. Several existing pharmacotherapies have been targeted for off-label benefit in traumatic brain injury, as these agents are well characterized and commercially available, easing the process of clinical trial development. Despite promising results in animal models, clinical trials have demonstrated minimal benefit. One possible reason for these failed translations could be that drug selection, characterization and dosing are not routinely established in the appropriate early phase trials before larger scale testing. Examining how recent trials may have bypassed these steps may help future trials to more definitively determine the efficacy of potential therapeutics.

Off-label drug use in hospitalized children: a prospective observational study at Gondar University Referral Hospital, Northwestern Ethiopia.

Most of the medications which are currently used for the treatment of childhood diseases are either not licensed or being prescribed outside the terms of the product license (off‐label prescribing). This study aimed at determining the extent of unlicensed and off‐label drug uses and associated factors in children hospitalized in Gondar University Referral Hospital, Northwest Ethiopia. An institution‐based prospective cross‐sectional study was employed from April 15 to July 15, 2016. A total of 243 pediatric patients admitted to Gondar university referral hospital were included in the study using simple random sampling method. Data were collected using structured questionnaire, and the data collected were entered and analyzed using Statistical Packages for Social Sciences (SPSS) version 20. From the total of 800 drugs prescribed, 607 (75.8%) were off‐label. Off‐label medicine use was frequently observed in antimicrobials (60.6%) followed by central nervous system drugs (14.3%). The extent off‐label prescribing was highest in age group of 6–13 years (30%). Inappropriate dosing and frequency (42.3%) were the most common reason for off‐label medicine use. Having other variables controlled, age group and undergoing surgical procedure remained to be significant predictors of off‐label prescribing in the multivariate regression analysis. Implementing evidence‐based approach in prescribing by generating more quality literatures on the safety profile and effectiveness of off‐label would improve the injudicious use of drugs in pediatric population.

Tissue-specific tumorigenesis: context matters.

How can we treat cancer more effectively? Traditionally, tumours from the same anatomical site are treated as one tumour entity. This concept has been challenged by recent breakthroughs in cancer genomics and translational research that have enabled molecular tumour profiling. The identification and validation of cancer drivers that are shared between different tumour types, spurred the new paradigm to target driver pathways across anatomical sites by off-label drug use, or within so-called basket or umbrella trials which are designed to test whether molecular alterations in one tumour entity can be extrapolated to all others. However, recent clinical and preclinical studies suggest that there are tissue- and cell type-specific differences in tumorigenesis and the organization of oncogenic signalling pathways. In this Opinion article, we focus on the molecular, cellular, systemic and environmental determinants of organ-specific tumorigenesis and the mechanisms of context-specific oncogenic signalling outputs. Investigation, recognition and in-depth biological understanding of these differences will be vital for the design of next-generation clinical trials and the implementation of molecularly guided cancer therapies in the future.

Drug utilization study of off-label drug use in outpatient department of psychiatry: a prospective study at a tertiary care teaching hospital

Background: In the absence of standard psychiatric prescribing information, physician often use drugs in an off-label way. Many studies have been published across the globe reporting different rates of off-label use. There is currently no study based on Indian Drug Formulary.Methods: After taking permission from Institutional Ethics Committee (IEC), a prospective study was conducted among 285 patients attending Psychiatry outpatient department for the period of 4 months. Data related to demographic parameters, diagnosis of psychiatry conditions and drugs details were collected directly from the patient's medical records and entered in Case Record Form (CRF).The off-label drugs were categorized as per National Formulary of India. Multivariate binary logistic regression model was used to determine the predictors of off- label drug prescribing. The data were statistically analyzed using SPSS version 19 and chi-square test.Results: A total of 285 patients (169 males, 116 females) were included in the study with mean age of 36.54±13.91 years. Most of the patients (n=65, 22.8%) were diagnosed as schizophrenic. Out of 285 patients, 133(46.6%) received at least one off-label drug. A total 841 drugs were prescribed out of which 167(19.85%) were off-label. The drug most frequently prescribed as off-label were trihexiphenidyl HCL 29 (10.2%), clozapine 23 (8.1%) and clonazepam 13 (4.6%).Conclusions: Off label drugs used among psychiatry patients was 19.85%. The most frequently used off-label drugs was trihexiphenidyl HCL. The use of off-label drugs in psychiatric patients has been reportedly increasing which warrant national drug regulatory authorities to review and revise safe administration such drugs.

Off-label drug use in oncology: a systematic review of literature.

The off-label use of medicines is widespread in several diseases. This type of prescribing practice is particularly more acute in oncology. However, the suitability of anticancer medications for off-label use remains an issue of controversy, due to uncertainty around the clinical benefits and potential toxicities, limited evidence to support clinical decision-making, increased out-of-pocket costs for patients and ethical concerns around the lack of informed consent. Currently, data pertaining to the global prevalence of off-label use in cancer therapy are lacking. The aim of this review was to provide an overview of off-label drug use prevalence in oncology. A systematic literature search was performed in PubMed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines from 1975 to 2016. Studies assessing the prevalence of off-label use of anticancer drugs were included. Of the 199 eligible papers retrieved, 23 studies were included in this systematic literature review. Off-label drug use in inpatients ranged from 18% to 41%. Among adult patients with cancer, 13%-71% received a minimum of one off-label chemotherapy. The main reasons for off-label drug use were 'drug unapproved for specific tumour' and 'modified drug applications'. Among adults, metastatic cancers and palliative care patients received the most off-label drugs. The off-label drug use unsupported by standard treatment guidelines or drug compendia was in the range of 7%-31%. Off-label drug use in cancer therapy is commonly practised but outcomes could vary significantly. Hence, greater scrutiny and robust clinical guidance is needed to establish the favourable benefit-risk ratio for patients at the time of prescribing at each level of oncology care to facilitate rational off-label prescribing.

A study on off-label and unlicensed drug use by community pharmacists: A report from resource-limited settings of South India

Introduction: Labeled uses of drug use are approved by the regulatory authorities based on preclinical and clinical data which confirms their safety and efficacy. From the community pharmacist perspective, the most common off-label use is due to physician's prescriptions and usage of over-the-counter (OTC) medications. In India, huge number of medicines is easily available for off-label use from the community pharmacists with or without prescriptions. Objectives: It is a preliminary study to evaluate and describe the off-label drug use by community pharmacists in resource-limited settings. Materials and Methods: It is a prospective cross-sectional study conducted among community pharmacies located in and around of Anantapur district, a rural part of Andhra Pradesh, South India. The data were collected through questionnaire-based semi-structured interview and/or asked the community pharmacists to complete on their own at the spot to avoid manipulation of data. The questionnaire is of two types: the first type evaluates pharmacist perspective on off-label indication for randomly selected drugs (frequent moving) and the second type evaluates dispensing practice of drugs for off-label use based on symptoms. Results: The present study results show that the frequency of off-label drug use is high among community pharmacists; moreover, they dispense the drugs without aware of off-label or inappropriate indication, sometimes as OTC medications. It is an acceptable fact that off-label or unlicensed drug use is not illegal but has plenty of safety and other issues. Conclusion: Thus, the present study provides a preliminary data to frame future educational and interventional programs to improve the rational use of drugs with regard to it.

Pharmaceutical Use and Spending Trend in Medicare Beneficiaries With Dementia, From 2006 to 2012.

Objectives: The aim of the study was to examine the trend in incidence and prevalence of dementia, use and spending of antidementia and antipsychotic drugs among dementia patients. Methods: Using 2006-2012 Medicare claims data, we identified individuals with diagnosis of dementia and collected their pharmacy claims in 2006-2012. We built regression models to test the trend in number of prescriptions and spending on antidementia, antipsychotic, and other drugs. Results: The prevalence of dementia did not change during our study period. Spending on antidementia and antipsychotic drugs creased to increase in 2011, following the patent expiration of Aricept, Zyprexa, and Seroquel; and total pharmaceutical spending did not change in 2006-2012. Use of antidementia drugs increased during our study period; however, the off-label use of antipsychotic drugs did not decrease. Discussion: Pharmaceutical spending associated with dementia may not be as concerning for Medicare as previously thought; nevertheless, policies that discourage the nonevidence-based off-label use of drugs are warranted.

Off-label and unlicensed drug use: Results from a pilot study in a paediatric intensive care unit

Abstract Purpose To analyze the prevalence of use of off-label and unlicensed drugs in a paediatric intensive care unit of a University Hospital. Method An observational, descriptive, prospective six week pilot study in a paediatric intensive care unit. Hospitalized patients aged between 0 and 18 years were included. Each prescribed drug was evaluated taking into account indication and condition of use, according to the information available on the summary of product characteristics established by the European Medicines Agency. A sequential algorithm was defined allowing drug classification in unlicensed, off-label or approved. Results 42 patients were included. A total of 696 prescriptions, involving 102 different drugs, were analyzed. All patients had at least one off-label prescription, and a median of 8.9 off-label prescriptions were obtained. Of the total prescriptions, 8.6% were unlicensed and 53.9% corresponded to off-label use. The main reason for off-label use was by indication, followed by age and dose. A lineal tendency between off-label drug use and patient age was observed, where off-label use increased as patient age decreased. The drugs most commonly used off-label were: atropine, etomidate, dipyrone and ranitidine, and unlicensed drugs: spironolactone, sildenafil, acetazolamide and hydrochlorothiazide. Conclusion Paediatric intensive care units are characterized by a high ratio of off-label and unlicensed prescriptions. The scarce number of studies performed in this specific and complex sub-population added inconveniency to the current lack of data on safety and efficacy for drugs in paediatrics. Performing studies with these characteristics allowing us to document practice on paediatric drug utilization is required.

Off-label use of antibacterial agents in Traffic Hospital of Shandong Province in 2016: a cross sectional study

Objective To determine the off-label use of antibacterial agents, we investigated and analyzed the current status about off-label use of antibacterial agents. Methods The random sampling was conducted to select the outpatient prescription including antibacterial agents from January to April in 2016.According to drug instructions, the off-label drug use of prescription was analyzed. Results 1 264 prescriptions involving 58 kinds of drugs were analyzed.The main categories of off-label drug use were no pediatric and elderly information(23.42%), indication(4.15%), dosage(6.31%), dosage range(62.95%) and administration route(3.15%). Conclusion The off-label use of antibacterial agents is common in our hospital.It's in need to regulate off-label drug use. Key words: Prospectuses; Drug prescriptions; Anti-bacterial agents; Ambulatory care

OFF-LABEL PRESCRIBING. POSSIBLE CAUSES, TYPES AND CONSEQUENCES. LEGAL REGULATION IN THE RUSSIAN FEDERATION

The off-label prescribing is multifaceted problem and affects the interests and scope of activities of different parties. Possible reasons, types of offlabel use of drugs are given in the article, as well as legal regulation of this issue in the Russian Federation and abroad. Such type of prescriptions is broad in various fields of medicine, especially in pediatrics, oncology, obstetrics and gynecology. Often this is due to the inability to perform appropriate randomized clinical studies, because of regulatory difficulties, economic inexpediency and ethical considerations. An additional complication in regulating this process is the fact that in the Russian Federation there is no clear legal basis for the off-label use of drugs, as well as the fact that clinical recommendations do not have a legal status. It seems relevant to study the assessment of the consequences of off-label drugs use, especially long-term effects. For this purpose, it seems important to use existing medical registers, as well as to create new prospective registers devoted to the study of the consequences of off-label prescribing.

Off-label use of drugs in regional anesthesia: A need for setting up policies.

Off-label use of drugs in regional anesthesia: A need for setting up policies.

OP120 Recommendations From The Newly Developed French National Authority For Health (HAS) Guide On Budget Impact

INTRODUCTION:Budget impact analysis (BIA) provides short and medium-term estimated effect of new health interventions on budgets and resources. Since January 2016, BIA is required as part of economic dossiers submitted to the French National Authority for Health (HAS) by manufacturers for innovative drugs with an expected 2-year sales revenue above EUR50 million. To this end and in order to promote good practices for conducting BIA, HAS developed a guide for BIA.Our objectives are: –to present the guide development method and the resulting recommendations;–to compare the HAS BIA guide with existing BIA guides.METHODS:The HAS guide development process rests on findings derived from a systematic literature review on BIA methodology, an HAS retrospective investigation of BIA, public consultation, international expert advice, and approval from the HAS Board and Committee of Health Economic and Public Evaluation (CEESP). Relevant publications were identified through Pubmed and EMBASE and the grey literature (search dates: January 2000 to June 2016).RESULTS:The search strategy captured 144 publications of which 31 were retained (14 methodological papers, 12 national guides and 5 learned society recommendations). On the basis of this result, an extraction template was designed to synthesize the methodological aspects of BIA. Based on its research findings, HAS developed its first BIA guide which includes recommendations on the following main topics: BIA definition, perspective, populations, time horizon, compared scenarios, BIA models, costing, discounting, choice of clinical data, reporting of BIA and uncertainty exploration.Compared to existing BIA guides from other Health Technology Assessment (HTA) agencies, the HAS guide specifically described issues relating to off-label use of drugs, disease-related costs and scenario analysis.CONCLUSIONS:It is expected that the HAS BIA guide will improve the quality, transparency and standardization of BIA in France. It should also enhance the usefulness of BIA as an essential part of a comprehensive economic assessment of health care interventions.