scholarly journals Healthy Volunteer Studies in the Development of Anticancer Drugs with Genotoxic Findings

2021 ◽  
Author(s):  
Grace Omes-Smit ◽  
Marjolein Garsen ◽  
Alex Zwiers
Keyword(s):  
Clinical Trials ◽  
Anticancer Drugs ◽  
Exposure Dose ◽  
Cell System ◽  
General Information ◽  
European Medicines Agency ◽  
Genetic Toxicology ◽  
Toxicology Screening ◽  
Available Information ◽  
The Eu

Abstract Background Recent scientific advances in cancer research have led to the development of immunomodulatory and molecularly targeted drugs with better safety profiles than chemotherapeutics, which makes it possible to include healthy volunteers (HVs) in clinical trials. In this study, we aimed to identify the number of marketing authorization applications (MAAs) that enrolled HVs in a clinical trial and to identify the number of anticancer drugs that were given to HVs despite a positive genotoxic finding. In addition, we evaluated the dose of anticancer drugs administered to HVs and the justification for proceeding with HV studies despite a positive genotoxic finding. Methods Publicly available information from the European Medicines Agency (EMA) website was used for this study. Anticancer drugs were identified using the human medicines highlights published by EMA between January 2010 and December 2019. EPARs were used to collect general information of the anticancer drugs, details on genotoxicity studies, and the enrollment of HVs in clinical trials. Results We identified 71 MAAs for small molecule anticancer drugs with a positive or negative CHMP opinion in the EU. Forty-eight anticancer drugs were studied in HVs, of which 12 anticancer drugs were administered to HVs despite positive genotoxic findings in the standard battery. Systematic and extensive genetic toxicology screening demonstrated the absence of genotoxic risks to the cell system. Conclusion We showed that despite a positive genotoxic finding, comprehensive genetic toxicology testing demonstrated the absence of risks to the cell system at the human exposure dose. Therefore, these anticancer drugs posed no harm to HVs.

scholarly journals Do We Need to Use Bats as Bioindicators?

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 693
Author(s):  
Danilo Russo ◽  
Valeria B. Salinas-Ramos ◽  
Luca Cistrone ◽  
Sonia Smeraldo ◽  
Luciano Bosso ◽  
...  
Keyword(s):  
Scientific Evidence ◽  
Legal Obligation ◽  
Farming Practices ◽  
Population Declines ◽  
Technological Advances ◽  
River Quality ◽  
Surrogate Taxa ◽  
Available Information ◽  
Sampling Problems ◽  
The Eu

Bats show responses to anthropogenic stressors linked to changes in other ecosystem components such as insects, and as K-selected mammals, exhibit fast population declines. This speciose, widespread mammal group shows an impressive trophic diversity and provides key ecosystem services. For these and other reasons, bats might act as suitable bioindicators in many environmental contexts. However, few studies have explicitly tested this potential, and in some cases, stating that bats are useful bioindicators more closely resembles a slogan to support conservation than a well-grounded piece of scientific evidence. Here, we review the available information and highlight the limitations that arise in using bats as bioindicators. Based on the limited number of studies available, the use of bats as bioindicators is highly promising and warrants further investigation in specific contexts such as river quality, urbanisation, farming practices, forestry, bioaccumulation, and climate change. Whether bats may also serve as surrogate taxa remains a controversial yet highly interesting matter. Some limitations to using bats as bioindicators include taxonomical issues, sampling problems, difficulties in associating responses with specific stressors, and geographically biased or delayed responses. Overall, we urge the scientific community to test bat responses to specific stressors in selected ecosystem types and develop research networks to explore the geographic consistency of such responses. The high cost of sampling equipment (ultrasound detectors) is being greatly reduced by technological advances, and the legal obligation to monitor bat populations already existing in many countries such as those in the EU offers an important opportunity to accomplish two objectives (conservation and bioindication) with one action.

scholarly journals A Review of Repurposed Cancer Drugs in Clinical Trials for Potential Treatment of COVID-19

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 815
Author(s):  
Bárbara Costa ◽  
Nuno Vale
Keyword(s):  
Clinical Trials ◽  
Anticancer Drugs ◽  
Clinical Management ◽  
Scientific Discovery ◽  
Immune Dysfunction ◽  
Potential Treatment ◽  
Medical Treatments ◽  
Prevention And Treatment ◽  
Rapid Pace ◽  
Effective Drugs

The pandemic of the coronavirus disease 2019 (COVID-19) represents an unprecedented challenge to identify effective drugs for prevention and treatment. While the world’s attention is focused on news of COVID-19 vaccine updates, clinical management still requires improvement. Due to the similarity of cancer-induced inflammation, immune dysfunction, and coagulopathy to COVID-19, anticancer drugs, such as Interferon, Pembrolizumab or Bicalutamide, are already being tested in clinical trials for repurposing, alone or in combination. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected, clinicians need effective medical treatments for this infection.

scholarly journals The Biosimilar Landscape: An Overview of Regulatory Approvals by the EMA and FDA

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 48
Author(s):  
Ioana Gherghescu ◽  
M. Begoña Delgado-Charro
Keyword(s):  
Drug Administration ◽  
Action Plan ◽  
European Medicines Agency ◽  
Patient Access ◽  
Clinical Evaluations ◽  
The Past ◽  
The Us ◽  
Improve Patient ◽  
The Eu

Biosimilar medicines expand the biotherapeutic market and improve patient access. This work looked into the landscape of the European and US biosimilar products, their regulatory authorization, market availability, and clinical evaluation undergone prior to the regulatory approval. European Medicines Agency (EMEA, currently EMA) and Food and Drug Administration (FDA) repositories were searched to identify all biosimilar medicines approved before December 2019. Adalimumab biosimilars, and particularly their clinical evaluations, were used as a case study. In the past 13 years, the EMA has received 65 marketing authorization applications for biosimilar medicines with 55 approved biosimilars available in the EU market. Since the first biosimilar approval in 2015, the FDA has granted 26 approvals for biosimilars with only 11 being currently on the US market. Five adalimumab biosimilars have been approved in the EU and commercialized as eight different medicines through duplicate marketing authorizations. Whilst three of these are FDA-approved, the first adalimumab biosimilar will not be marketed in the US until 2023 due to Humira’s exclusivity period. The EU biosimilar market has developed faster than its US counterpart, as the latter is probably challenged by a series of patents and exclusivity periods protecting the bio-originator medicines, an issue addressed by the US’s latest ‘Biosimilar Action Plan’.

scholarly journals Reporting of harms in oncological clinical study reports submitted to the European Medicines Agency compared to trial registries and publications—a methodological review

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Asger S. Paludan-Müller ◽  
Perrine Créquit ◽  
Isabelle Boutron
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Study ◽  
Primary Source ◽  
European Medicines Agency ◽  
Clinical Trial Registries ◽  
Number Of Patients ◽  
Journal Publications ◽  
Clinical Study Reports ◽  
Completeness Of Reporting

Abstract Background An accurate and comprehensive assessment of harms is a fundamental part of an accurate weighing of benefits and harms of an intervention when making treatment decisions; however, harms are known to be underreported in journal publications. Therefore, we sought to compare the completeness of reporting of harm data, discrepancies in harm data reported, and the delay to access results of oncological clinical trials between three sources: clinical study reports (CSRs), clinical trial registries and journal publications. Methods We used the EMA clinical data website to identify all trials submitted to the EMA between 2015 and 2018. We retrieved all CSRs and included all phase II, II/III or III randomised controlled trials (RCTs) assessing targeted therapy and immunotherapy for cancer. We then identified related records in clinical trial registries and journals. We extracted harms data for eight pre-specified variables and determined the completeness of reporting of harm data in each of the three sources. Results We identified 42 RCTs evaluating 13 different drugs. Results were available on the EMA website in CSRs for 37 (88%) RCTs, ClinicalTrials.gov for 36 (86%), the European Clinical Trials Register (EUCTR) for 20 (48%) and in journal publications for 32 (76%). Harms reporting was more complete in CSRs than other sources. We identified marked discrepancies in harms data between sources, e.g. the number of patients discontinuing due to adverse events differed in CSRs and clinical trial registers for 88% of trials with data in both sources. For CSRs and publications, the corresponding number was 90%. The median (interquartile range) delay between the primary trial completion date and access to results was 4.34 (3.09–7.22) years for CSRs, 2.94 (1.16–4.52) years for ClinicalTrials.gov, 5.39 (4.18–7.33) years for EUCTR and 2.15 (0.64–5.04) years for publications. Conclusions Harms of recently approved oncological drugs were reported more frequently and in more detail in CSRs than in trial registries and journal publications. Systematic reviews seeking to address harms of oncological treatments should ideally use CSRs as the primary source of data; however, due to problems with access, this is currently not feasible.

scholarly journals A Decade of Marketing Authorization Applications of Anticancer Drugs in the European Union: An Analysis of Procedural Timelines

2021 ◽  
Author(s):  
Marjolein Garsen ◽  
Maaike Steenhof ◽  
Alex Zwiers
Keyword(s):  
Anticancer Drugs ◽  
Marketing Authorization ◽  
European Medicines Agency ◽  
Company Size ◽  
Scientific Advice ◽  
The European Union ◽  
Small Companies ◽  
Procedure Time ◽  
Total Procedure Time ◽  
Total Procedure

Abstract Background Cancer is a serious global health problem and a major cause of death. The European Medicines Agency (EMA) has established several regulatory initiatives to expedite the development and authorization of drugs to ensure timely access of patients. In this study, we analyzed the procedural timelines of marketing authorization applications for anticancer drugs in the EU, with a specific focus to special regulatory programs, scientific advice and company size. Methods Anticancer drugs that received an opinion from the EMA between January 2010 and December 2019 were included in the study. Public assessment reports were used to obtain publicly available information of the drugs. Results We identified 96 applications for new anticancer drugs. 34 applications were granted access to at least one expedited program offered by the EMA. Total procedure time was reduced from average 370 to 200–215 days when accelerated assessment was granted. Granting of a conditional marketing authorization or an orphan designation, as well as having scientific advice, only mildly affected total procedure time. Average total procedure time of small companies was much longer compared with medium-sized and large companies (483 versus 356 days), which was caused by an increased clock stop time. Conclusion Total procedure time for anticancer is mainly affected by the granting of accelerated assessment, which reduced the total procedure time, and company size, where total procedure time is much longer for small companies. Small companies are advised to have, and especially adhere to scientific advice to reduce procedure time and increase the chance of success.

scholarly journals Redundant trials can be prevented, if the EU clinical trial regulation is applied duly

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Daria Kim ◽  
Joerg Hasford
Keyword(s):  
Clinical Trials ◽  
Health Risks ◽  
Ethics Committees ◽  
Medical Community ◽  
Significant Extent ◽  
Regulatory Requirements ◽  
Trial Participants ◽  
Clinical Trials Regulation ◽  
Clinical Trial Regulation ◽  
The Eu

Abstract The problem of wasteful clinical trials has been debated relentlessly in the medical community. To a significant extent, it is attributed to redundant trials – studies that are carried out to address questions, which can be answered satisfactorily on the basis of existing knowledge and accessible evidence from prior research. This article presents the first evaluation of the potential of the EU Clinical Trials Regulation 536/2014, which entered into force in 2014 but is expected to become applicable at the end of 2021, to prevent such trials. Having reviewed provisions related to the trial authorisation, we propose how certain regulatory requirements for the assessment of trial applications can and should be interpreted and applied by national research ethics committees and other relevant authorities in order to avoid redundant trials and, most importantly, preclude the unnecessary recruitment of trial participants and their unjustified exposure to health risks.

scholarly journals A Healthy Sense of Trust

2017 ◽  
Vol 2 (Suppl. 1) ◽  
pp. 1-10
Author(s):  
Denis Horgan
Keyword(s):  
European Union ◽  
Clinical Trials ◽  
Big Data ◽  
Data Protection ◽  
Fast Moving ◽  
Ethical Issues ◽  
Personalised Medicine ◽  
Drug Pricing ◽  
The Right ◽  
The Eu

In the fast-moving arena of modern healthcare with its cutting-edge science it is already, and will become more, vital that stakeholders collaborate openly and effectively. Transparency, especially on drug pricing, is of paramount importance. There is also a need to ensure that regulations and legislation covering, for example the new, smaller clinical trials required to make personalised medicine work effectively, and the huge practical and ethical issues surrounding Big Data and data protection, are common, understood and enforced across the EU. With more integration, collaboration, dialogue and increased trust among each and every one in the field, stakeholders can help mould the right frameworks, in the right place, at the right time. Once achieved, this will allow us all to work more quickly and more effectively towards creating a healthier - and thus wealthier - European Union.

scholarly journals Biosimilars in the French and Polish System: Chosen Aspects of Reimbursement and Access

2020 ◽  
Vol 23 (2) ◽  
pp. 103-115
Author(s):  
Olga Barszczewska ◽  
Ralph Chami ◽  
Anna Piechota
Keyword(s):  
Public Expenditure ◽  
Drug Expenditure ◽  
European Medicines Agency ◽  
Treatment Results ◽  
Policy Goal ◽  
Ministry Of Health ◽  
Biological Drugs ◽  
Reimbursement List ◽  
Considerable Experience ◽  
The Eu

The EU approved the first biosimilar drug in 2006. By 2017, the EU had authorized the highest number of biosimilars worldwide, acquiring considerable experience in their use and safety. In May 2019, the European Medicines Agency (EMA) search engine showed 54 authorized biosimilars. Biosimilars reduce public expenditure; however, the discussion about their potential disadvantages is still ongoing. Each country adopts different regulations on the interchangeability, switching, and substitution of a reference medicine by its biosimilar, since the EMA does not regulate this issue. Additionally, each nation has a unique reimbursement system, which results in significant differences in patients’ access to biosimilars. The importance of securing a higher availability of these cheaper versions of biological drugs is well-recognized. The better the access to these biosimilars is, the lower the overall drug expenditure and need for rationing would be, and therefore the better treatment results. The aim of this paper is to compare selected aspects of reimbursement and access to the EMA authorized biosimilar medicines in two countries – France and Poland. The stated drug policy goal of both countries is to significantly improve biosimilar implementation in the coming years. The research is based on an analysis of four main sources: the EMA biosimilars database, the Polish reimbursement list published by the Polish Ministry of Health, and two French reimbursement databases published by the French Ministry of Health. An additional literature review was conducted. The expected results concentrate on differences in the number of reimbursed biosimilars, the average time between EMA authorization and country reimbursement decision date, and the availability of biosimilars registered outside of the centralized (EMA) procedure. These findings could identify areas of improvement and help with discussions on how to optimize the reach of biosimilars, as well as improve French-Polish collaboration on this matter.

scholarly journals Differences between the European and Eurasian Good Pharmacovigilance Practices

2021 ◽  
Vol 9 (2) ◽  
pp. 75-84
Author(s):  
A. V. Matveev ◽  
A. E. Krasheninnikov ◽  
E. A. Matveeva ◽  
B. K. Romanov
Keyword(s):  
Marketing Authorisation ◽  
European Medicines Agency ◽  
The European Union ◽  
Current Version ◽  
Eurasian Economic Union ◽  
Expert Analysis ◽  
The Russian Federation ◽  
Economic Union ◽  
Systems Effectiveness ◽  
The Eu

Good pharmacovigilance practices (GVP) of the Eurasian Economic Union (EAEU) were prepared based on the GVP of the European Medicines Agency that have been in force in the European Union (EU) since 2012. The EAEU GVP have been in force in the Russian Federation and the other EAEU member states since 2016. It is important to identify potential differences between the current regulations in order to harmonise requirements for the pharmacovigilance systems in the EU and EAEU. The aim of the study was to analyse and compare GVP requirements in the EU and EAEU. The analysis helped to identify differences in the structure and contents of GVP sections, the definitions of terms (EU GVP definitions are more detailed and supported by examples, subsections, and references to other documents). Moreover, supplements and annexes to the EU GVP contain figures, templates, examples, algorithms, and tables, which are missing in the EAEU GVP. Expert analysis of these differences as applied to assessment of the pharmacovigilance systems’ effectiveness, and practical activities of marketing authorisation holders, medicine developers, and regulatory authorities, demonstrated that the two GVPs are sufficiently harmonised and have very few differences. However, the number of differences between the documents increases, as changes are made to the EU GVP. A more comprehensive harmonisation of the EAEU GVP with the current version of the EU GVP will make it possible to develop and use uniform pharmacovigilance documents in the EU and EAEU, and will facilitate the introduction of EAEU medicines into the global pharmaceutical market.

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