Why Were More Than 200 Subjects Required to Demonstrate the Bioequivalence of a New Formulation of Levothyroxine with an Old One?

At the request of French Regulatory Authorities, a new formulation of Levothyrox® was licensed in France in 2017, with the objective of avoiding the stability deficiencies of an existing licensed formulation. Before launching the new formulation, an average bioequivalence (ABE) trial was conducted, having enrolled 204 subjects and selected for interpretation a narrow a priori bioequivalence range of 0.90–1.11. Bioequivalence was concluded. In a previous publication, we questioned the ability of an ABE trial to guarantee the switchability within patients of the new and old levothyroxine formulations. It was suggested that the two formulations should be compared using the conceptual framework of individual bioequivalence. The present paper is a response to those claiming that, despite the fact that ABE analysis does not formally address the switchability of the two formulations, future patients will nevertheless be fully protected. The basis for this claim is that the ABE study was established in a large trial and analyzed using a stringent a priori acceptance interval of equivalence. These claims are questionable, because the use of a very large number of subjects nullifies the implicit precautionary intention of the European guideline when, for a Narrow Therapeutic Index drug, it recommends shortening the a priori acceptance interval from 0.80–1.25 to 0.90–1.11

Self-medication and non-doctor prescription practices in Pokhara valley, Western Nepal: a questionnaire-based study

BACKGROUND: Self-medication and non-doctor prescribing of drugs is common in developing countries. Complementary and alternative medications, especially herbs, are also commonly used. There are few studies on the use of these medications in Pokhara Valley, Western Nepal. METHODS: Previously briefed seventh semester medical students, using a semi-structured questionnaire, carried out the study on 142 respondents. Demographic information and information on drugs used for self-medication or prescribed by a non-allopathic doctor were collected. RESULTS: Seventy-six respondents (54%) were aged between 20 to 39 years. The majority of the respondents (72 %) stayed within 30 minutes walking distance of a health post/medical store. 59% of these respondents had taken some form of self-medication in the 6-month period preceding the study. The common reasons given for self-medication were mild illness, previous experience of treating a similar illness, and non-availability of health personnel. 70% of respondents were prescribed allopathic drugs by a non-allopathic doctor. The compounder and health assistant were common sources of medicines. Paracetamol and antimicrobials were the drugs most commonly prescribed. A significantly higher proportion of young (<40 years) male respondents had used self-medication than other groups. CONCLUSIONS: Self-medication and non-doctor prescribing are common in the Pokhara valley. In addition to allopathic drugs, herbal remedies were also commonly used for self-medication. Drugs, especially antimicrobials, were not taken for the proper duration. Education to help patients decide on the appropriateness of self-medication is required

P73 Preliminary results of the Study of Acute Liver Transplant (SALT): NSAID exposure and risk of acute liver failure leading to transplantation in 7 European countries

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Drug safety of rosiglitazone and pioglitazone in France: a study using the French PharmacoVigilance database

International audienceBackgroundThiazolidinediones (TZDs), rosiglitazone (RGZ) and pioglitazone (PGZ) are widely used as hypoglycemic drugs in patients with type 2 diabetes mellitus. The aim of our study was to investigate the profile of adverse drug reactions (ADRs) related to TZDs and to investigate potential risk factors of these ADRs.MethodsType 2 diabetic patients were identified from the French Database of PharmacoVigilance (FPVD) between 2002 and 2006. We investigated ADR related to TZD, focusing on 4 ADR: edema, heart failure, myocardial infarction and hepatitis corresponding to specific WHO-ART terms.ResultsAmong a total of 99,284 adult patients in the FPVD, 2295 reports concerned type 2 diabetic patients (2.3% of the whole database), with 161 (7%) exposed to TZDs. The frequency of edema and cardiac failure was significantly higher with TZDs than in other patients (18% and 7.4% versus 0.8% and 0.1% respectively, p ConclusionsThiazolidinediones exposure is associated with an increased risk of edema and heart failure in patients with type 2 diabetes even when recommendations for use are respected. In contrast, the risk of hepatic reactions and myocardial infarction with this class of drugs seems to be similar to other hypoglycemic agents

Dedicated mobile application for drug adverse reaction reporting by patients with relapsing remitting multiple sclerosis (Vigip-SEP study): study protocol for a randomized controlled trial

BackgroundThe reporting of adverse drug reactions (ADR) by patients represents an interesting challenge in the field of pharmacovigilance, but the reporting system is not adequately implemented in France. In 2015, only 20 MS patients in France reported ADR due to first-line disease-modifying drugs (DMD), while more than 3000 patients were initiated on DMD.The aim of this study is to validate a proof-of-concept as to whether the use of a mobile application (App) increases ADR reporting among patients with relapsing-remitting multiple sclerosis (RR-MS) receiving DMD.Methods/designWe designed a multi-centric, open cluster-randomized controlled trial, called the Vigip-SEP study (NCT03029897), using the App My eReport France® to report ADR to the appropriate authorities in E2B language, in accordance with European regulations. RR-MS patients who were initiated on, or switched, first-line DMD will be included. In the experimental arm, a neurologist will introduce the patient to the App to report ADR to the appropriate French authorities. In the control arm, the patient will be informed of the existence of the App but will not be introduced to its use and will then report ADR according to the usual reporting procedures. Primary assessment criteria are defined as the average number of ADR per patient and per center. We assume that the App will increase patient reporting by 10-fold. Therefore, we will require 24 centers (12 per arm: 6 MS academic expert centers, 3 general hospitals, 3 private practice neurologists), allowing for an expected enrollment of 180 patients (alpha risk 5%, power 90% and standard deviation 4%).DiscussionIncreasing patient reporting of ADR in a real-life setting is extremely important for therapeutic management of RR-MS, particularly for monitoring newly approved DMD to gain better knowledge of their safety profiles. To increase patient involvement, teaching patients to use tools, such as mobile applications, should be encouraged, and these tools should be tested rigorously