External control during RWD/RWE research: a methodological approach

At the moment, randomized controlled trials (RCTs) are the gold standard for providing evidence of the effectiveness and safety of medicines. If it is impossible to randomize and create an internal control group, alternative methods of collecting evidence are used, for example, the use of so-called external control groups created, among other things, based on real world data (RWD). The increase in the number of studies using RWD and external control is clearly visible in oncology, where there are problems with randomization classically. Meanwhile, this trend is of concern and requires a better understanding of the acceptability of using external control groups and validation of RWD

Determination of the reference value of the incremental cost-efficacy and cost-utility coefficient in Russia in oncology

The share of antineoplastic drug dossiers submitted to reimbursement in Russia raised from 15% in 2014 to 28% in 2017. The effectiveness and safety of innovative anti-cancer therapy is higher comparing to widely used traditional treatments. At the mean time the costs of innovative anti-cancer care are much higher, which request the incremental costs calculation. Aim. To determine the refence value of incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). Materials and methods. We analyzed health-economic (HE) studies submitted in the drug dossiers with ATC codes L01 and L02 to the reimbursement in Russia in 2014-2017. Life-years gained (LYG), cost of one LYG and cost of one quality adjusted life-year (QALY) gained we taken from HE studies. Subgroups of drugs included and not included in the reimbursement were compared. The reference cost of one LYG was calculated. Results. The median and geometric mean value of ICER/LYG and ICUR/QALY in the subgroup of drugs included in the reimbursement are 2 335 076 RUR/LYG and 2 343 954 RUR/QALY, consequently. Median and geometric mean of ICER/LYG in the subgroup of drugs included and in the reimbursement are by 33% and 21% lower comparing to the subgroup of drugs not included in the reimbursement. Median and geometric mean of cost of one QALY gained is 2 324 906 RUR/QALY. Conclusion. The reference value of ICER/LYG and ICUR is in the interval 2 300 000 - 2 500 000 RUR

Assessment of the economic feasibility of gadoversetamida (OptiMARK) MRI with intravenous contrast

Gadolinium based contrast agents are widely used in MRI in a diagnostic of variety of pathologies. The quality of contrast enhancement depends on the total dose. The aim of the study is to conduct a health economic evaluation of gadoversetamide (OptiMARK, Malickrodt Pharmaceuticals) in contrast enhanced MRI. The cost-effectiveness analysis, costminimizing analysis and sensitivity analysis and budget impact analysis were used modeling contrast enhanced MRI. In results, we can say that OptiMARK is cost-effective comparing to gadopentetic acid and gadobutrol

Assessment of the economic evaluation of the contrast agent Iomeron in percutaneous coronary intervention

Percutaneous coronary intervention (PCI — angiography and stent placement) aren’t possible without X-ray contrast agents. Contrast enhancement depends on the iodine concentration, while the safety of particular contrast agents diff ers. Th e aim of the study is to conduct health economic evaluation of Iomeron (Bracco Imaging S.p.A., Italy) in patients with acute coronary artery disease treating with PCI. Th e cost-eff ectiveness analysis, cost-minimization analysis, sensitivity analysis and budget impact analysis were used. In results, we can say that Iomeron is cost-eff ective comparing to iodixanol, iohexol, iopromide and ioversol

Assessment of the economic evaluation of the contrast agent MultiHance

Gadolinium based contrast agents are widely used in MRI in a diagnostic of variety of pathologies. The quality of contrast enhancement depends on the total dose (mM per kg body weight) and its relaxivity. Gadobenic acid (MultiHance® , Bracco Imaging S.p.A, Italy) has the highest relaxivity comparing to others gadolinium based contrast agents approved in Russia. The aim of the study is to conduct a health economic evaluation of gadobenic acid in contrast enhanced MRI. The cost effectiveness analysis, sensitivity analysis and budget impact analysis were used to modeling MRI of CNS, MR-angiography and MRI of the liver. In results, we can say that Multihance® is cost-effective comparing to gadopentetic acid, gadobutrol and gadodiamid in CNS MRI

Pharmacoepidemiology of botulinum toxin in the complex therapy of post-stroke spasticity in the Russian Federation. The survey data of neurologists

A pharmacoepidemiology study was performed of the use of botulinum toxin type A drugs (BTA) in the combined therapy of post-stroke spasticity in Russian Federation. Experts survey was the major method used and followed by application of the Delphi method. Questionnaire consisted of 30 questions. 12 completed questionnaires from 12 cities of Russia were analyzed as a result. Practicing neurologist participated in the survey who had experience of BTA use in combined treatment of post-stroke spasticity. Several indicators were identifi ed that represent signifi cant interest for their subsequent use, in particular, during the pharmacoeconomic studies, scientifi c analysis of outcomes with Markov modelling use, development of mathematical models

Nonsteroidal anti-inflammatory drugs’ adverse drug reactions: 10 years of national database data

The group of non-steroidal anti-inflammatory drugs has occupied one of the leading positions in terms of demand by the population over the past decade. This fact is explained by non-prescription sale, a wide range of purposes and an affordable price range. The lack of proper control over the use of non-steroidal anti-inflammatory drugs (NSAIDs) greatly complicates the assessment of safety, timely detection and prevention of events associated with patient’ safety. Target. Evaluation of data from the national pharmacovigilance database of the safety of non-steroidal anti-inflammatory drugs. Materials and methods. This is a cross-sectional study covering the period from 2010 till 2020. The assessment of the safety profile of international non-proprietary names (INN) from the group of NSAIDs at the post-registration stage was carried out according to the data of uploading the national database (Automated Information System of Roszdravnadzor; AIS RZN), as well as PubMed, Medline, Google Scholar, Elibrary databases. Conclusions. Over a ten-year period, the number of registered spontaneous messages was 8,334. With regard to the three international generic names, the number of adverse drug reactions prevails - this is metamizole (1875 (22.5 %)), acetylsalicylic acid (1716 (20.6 %)), diclofenac (979 (11.7 %)). The main system organ class with safety-related events are described for skin and subcutaneous structures. This fact is not consistent with the data of reference sources of information, which indicates the ineffectiveness of post-marketing observations by marketing authorization holders

Pragmatic clinical trials

Pragmatic clinical trials (PCTs) allow combining the advantages of observational trials in real-world evidence with the scientific rigor of randomized clinical trials (RCTs), and thereby provide more effective answers to questions of real-world evidence.Aim. Assessment of differences in conducting RCTs and PCTs, as well as analysis of the features related to conducting PCTs at different stages.Methods. An analysis of publications in the period from 1999 to 2017 was conducted to identify data on PCTs.Results. There are significant differences in conducting classic RCTs and PCTs. First, PCTs use more flexible inclusion criteria and differ in the approach to choosing an investigator’s site. Also, the procedure for obtaining informed consent has significant differences from that of classical RCTs; alternative options are proposed but a unified approach has not yet been developed. When conducting PCTs, monitor intervention should be minimal in order not to interfere in the routine therapy, which, however, can lead to a violation of reporting. A possible solution may be remote data collection.Conclusion. PCTs represent a huge potential for studying the effectiveness of drugs in real-world evidence. However, despite a significant increase in the number of such trials, there are still a sufficient number of points that need to be resolved

Applying real-world data to support regulatory decision — making in the United States

The article describes the legal basis for the application of real-world data to support regulatory decision-making in the United States, as well as the possibility of implementing the relevant approaches in the legislation of the Eurasian Economic Union