Extrapolation Of Clinical Data Research Articles

Environmental Occurrence and Predicted Pharmacological Risk to Freshwater Fish of over 200 Neuroactive Pharmaceuticals in Widespread Use.

There is a growing concern that neuroactive chemicals released into the environment can perturb wildlife behaviour. Among these chemicals, pharmaceuticals such as antidepressants and anxiolytics have been receiving increasing attention, as they are specifically prescribed to modify behavioural responses. Many laboratory studies have demonstrated that some of these compounds can affect various aspects of the behaviour of a range of aquatic organisms; however, these investigations are focused on a very small set of neuroactive pharmaceuticals, and they often consider one compound at a time. In this study, to better understand the environmental and toxicological dimension of the problem, we considered all pharmaceuticals explicitly intended to modulate the central nervous system (CNS), and we hypothesised that these compounds have higher probability of perturbing animal behaviour. Based on this hypothesis, we used the classification of pharmaceuticals provided by the British National Formulary (based on their clinical applications) and identified 210 different CNS-acting pharmaceuticals prescribed in the UK to treat a variety of CNS-related conditions, including mental health and sleep disorders, dementia, epilepsy, nausea, and pain. The analysis of existing databases revealed that 84 of these compounds were already detected in surface waters worldwide. Using a biological read-across approach based on the extrapolation of clinical data, we predicted that the concentration of 32 of these neuroactive pharmaceuticals in surface waters in England may be high enough to elicit pharmacological effects in wild fish. The ecotoxicological effects of the vast majority of these compounds are currently uncharacterised. Overall, these results highlight the importance of addressing this environmental challenge from a mixture toxicology and systems perspective. The knowledge platform developed in the present study can guide future region-specific prioritisation efforts, inform the design of mixture studies, and foster interdisciplinary efforts aimed at identifying novel approaches to predict and interpret the ecological implications of chemical-induced behaviour disruption.

Development, evaluation and use of COVID-19 vaccines in older adults: Preliminary principles for the pandemic and beyond.

Development, evaluation and use of COVID-19 vaccines in older adults: Preliminary principles for the pandemic and beyond.

Scientific rationale for extrapolation of biosimilar data across cancer indications: case study of CT-P10.

For a biosimilar to gain regulatory approval, a comprehensive comparability exercise must demonstrate that it is highly similar to its originator biologic, or reference product. Once biosimilarity has been shown, it is possible to approve the biosimilar for additional indications held by the reference product, without clinical trials in these indications. Extrapolation of clinical data is permitted by regulatory agencies as long as it is scientifically justified. CT-P10, a biosimilar of rituximab, was recently approved in Europe for all indications held by its reference product, incorporating both autoimmune diseases and hematological cancers. Here, we review the scientific rationale for extrapolation in biosimilar development using the example of CT-P10 as a case study.

Biosimilars in Oncology: From Development to Clinical Practice

Biologics play an integral role in the treatment of cancer not only for their therapeutic effects and ability to improve outcomes, but also as supportive care agents. Biologics are more complex to manufacture and take longer to bring to market. Because biologics are considerably more costly than small-molecule drugs, their use has placed an increasing economic demand on healthcare systems worldwide. Biosimilars are designed to be highly similar to existing branded biologics, but because biologics cannot be exactly copied, biosimilars should not be referred to as generic, exact versions of the innovator biologic. Biosimilars have the potential to increase access and provide lower cost options for cancer care as patent protection for some of the most widely used biologics begins to expire. Regulatory requirements for biosimilars are evolving, as are global harmonization and/or standardization strategies that can facilitate their robust clinical development. This review highlights critical factors involved with the integration of biosimilars into oncology treatment paradigms and practices. Clinicians will likely seek out practice guidelines and position statements from established scientific societies to help evaluate key information regarding biosimilars, such as efficacy, safety, comparability, and interchangeability with the reference biologic. Automatic substitution, nomenclature, extrapolation of clinical data from one indication to another, as well as parameters for ongoing pharmacovigilance are evolving considerations. Education of physicians and other healthcare providers, payers, and patients about biosimilars may facilitate informed decision making, promote acceptance of biosimilars into clinical practice, increase accessibility, and expedite associated health and economic benefits.

PMS60 - The Introduction Of Biosimilar Monoclonal Antibodies Into Developed Markets: What Are Payers Concerned About?

The introduction of biosimilar monoclonal antibodies into the market is thought to be eagerly awaited by payers. This is motivated by the need to constrain prescribing costs due to the ever burdening pressure on health care budgets. The objectives of this research were to explore payers’ attitudes towards the introduction of biosimiliars into the UK National Health Service, and to identify the key concerns of payers towards the entry of biosimilars into the market. As the UK is widely recognised as a leading health care market the outputs from this research can be applied to other developed markets. A thorough literature review was carried out identifying the current regulatory stance and other national guidance on the introduction of biosimilar monoclonal antibodies. From this a series of value messages were formulated around four themes: the manufacture of biosimilar monoclonal antibodies, extrapolation of clinical data, generic substitution and interchangeability and pharmacovigilance. These value messages were then tested with national payers to identify key priority areas. Payers identified that interchangeability and pharmacovigilance were the priority areas which needed to be addressed at both a national and local level to manage the entry of biosimilar monoclonal antibodies. In particular they identified immunogenicity as a key area of concern due to the long acting nature of biosimilar monoclonal antibodies. They also recommended a greater emphasis on the use of electronic prescribing systems to ensure that the appropriate recording of the originator product or biosimilar is documented and can be traced back to an individual patient. This should be mandated at a national level supported by local hospital protocols. Payers are aware of the introduction of biosimilar monoclonal antibodies into the market. They recognise that a managed entry assisted by the regulatory authorities alongside locally agreed guidance will be crucial to a successful roll-out.

Japanese guideline for clinical research of antimicrobial agents on urogenital infections: the first edition

In the 1970s, clinicians and researchers specializing in urinary tract infections (UTIs) established and published the first-ever Criteria for Clinical Evaluation of Drug Efficacy on UTI. There had so far been no uniform criteria for the evaluation of drug efficacy, and different criteria for determining drug efficacy had been used in the development of drugs, which had caused problems in determining drug efficacy and had made it impossible to compare efficacy between drugs. To resolve these challenges, the Criteria for Clinical Evaluation of Drug Efficacy on UTI were established on the basis of the results of a large number of studies. The late Dr. Masaaki Ohkoshi, the late Dr. Joji Ishigami, the late Dr. Tsuneo Nishiura, Dr. Toyohei Machida, Dr. Yoshiaki Kumamoto, Dr. Joichi Kumazawa, Dr. Yukimichi Kawada, Dr. Sadao Kamidono, and other senior physicians made efforts to create the world’s first Criteria for Clinical Evaluation of Drug Efficacy on UTI, which had contributed enormously to the development of antimicrobial agents for UTIs. In 1989, an International Symposium entitled ‘‘Clinical Evaluation of Drug Efficacy on UTI’’ was held in Tokyo and offered opportunities to get international recognition of the Criteria for Clinical Evaluation of Drug Efficacy on UTI. Thereafter, the International UTI Symposium was established and came to be held biennially in conjunction with the International Congress on Chemotherapy. The joint symposium has been held ten times to date. In Japan, the Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on UTI were created by the UTI study group. The Criteria, which were those of the revised 3rd edition, involved various urological infections, including prostatitis, epididymitis, and urethritis, in addition to UTIs. Meanwhile, Infectious Diseases Society of America (IDSA)/ Food and Drug Administration (FDA) guidelines and the Criteria for Clinical Evaluation of Drug Efficacy were established in theUnitedStates andEurope, respectively,which led to an increased need for international harmonization aswell as globalization of the development of antimicrobial agents. To move with the times and to allow compatibility between data accumulated in Japan and data fromother countries, the Study Group on Urology, the Committee of Clinical Evaluation Methods, and the Japanese Society of Chemotherapy discussed and created the 4th edition of Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on UTI (tentative) and its supplement in 1996. However, further international harmonization was needed, as international drug development, extrapolation of clinical data from other countries, and bridging studies had been increasing. In bringing about international M. Yasuda S. Takahashi H. Kiyota K. Ishikawa A. Takahashi S. Yamamoto S. Arakawa K. Monden T. Muratani R. Hamasuna H. Hayami T. Matsumoto UTI Subcommittee of the Clinical Evaluation Guidelines Committee, Japan Society of Chemotherapy, Tokyo, Japan

Extrapolation of Clinical Data from an Oral Glucose Tolerance Test Using a Support Vector Machine

To extract the important physiological factors related to diabetes from an oral glucose tolerance test (OGTT) by mathematical modeling, highly informative but convenient protocols are required. Current models require a large number of samples and extended period of testing, which is not practical for daily use. The purpose of this study is to make model assessments possible even from a reduced number of samples taken over a relatively short period. For this purpose, test values were extrapolated using a support vector machine. A good correlation was found between reference and extrapolated values in evaluated 741 OGTTs. This result indicates that a reduction in the number of clinical test is possible through a computational approach.