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Posted 03 February 2022 | By Nick Paul Taylor 

Euro Roundup: MHRA posts guidance on clinical trial risk assessments, oversight

2981 The UK Medicines & Healthcare products Regulatory Agency (MHRA) has published guidance on clinical trial risk assessments, oversight and monitoring in two new documents.
 
MHRA is asking sponsors to perform and document a risk assessment for each proposed clinical trial as early as possible to determine whether it falls under the Clinical Trials legislation, how the agency will categorize the trial and whether there are barriers to its execution.
 
“The risk assessment must be specific to the proposed trial and whilst the process may include templates or a guide on the areas to consider in the risk assessment, care should be taken to examine the potential risks of the proposed trial, which may present new areas that have not been considered in previous trials. This is why it is a bespoke approach,” the guidance states.
 
MHRA expects sponsors to form multidisciplinary teams, including a statistician and medic familiar with the therapeutic area, to conduct the risk assessment and to determine if additional review is needed. The additional review could involve senior management or be an independent peer review. MHRA is advising sponsors to conduct a review that is proportionate to the risks identified in the trial.
 
Sponsors should keep the risk assessment in the trial master file and, where appropriate, inform site staff of its content. As new information becomes available, such as after an interim analysis, MHRA expects sponsors to re-examine the risk assessment. The guidance also features three example risk assessments.
 
MHRA published the guidance on the same day as it released a document about the oversight and monitoring of investigational medical product trials. The second guidance document lists important factors in determining the oversight and monitoring strategy, explaining that sponsors should establish processes that reflect the known risks of a study. If an error in an activity would have a negative impact on participant safety and trial results, sponsors should make it a focus of oversight and monitoring.
 
The guidance represents a departure from the traditional approach of aiming to assess compliance with every detail of the protocol and check every data point against source documents. MHRA said that way of working is “extremely resource intensive.” The risk-based approach is intended to protect the rights, safety and wellbeing of the clinical trial participants and the reliability of the results without checking everything.
 
MHRA Guidance, More
 
 
MDCG posts general principles of clinical evidence for in vitro diagnostics
 
The Medical Device Coordination Group (MDCG) has released guidance on general principles of clinical evidence for in vitro diagnostics. MDCG published the document to support the evaluation process set out in the incoming In Vitro Diagnostic Regulation (IVDR).
 
Once IVDR comes into force, manufacturers will need to define the intended purpose of tests they plan to bring to market and generate clinical evidence showing the products perform as claimed. To support those activities, MDCG has described the general principles of clinical evidence, explaining how they differ from the principles for therapeutics, and detailed the performance evaluation process.
 
“When determining what data is needed to demonstrate the safety and performance of IVDs, it is important to consider available existing data and how to bridge any deficits. In the event that data is not available in either sufficient quality or quantity it will need to be generated,” the guidance states.
 
MDCG has set out a four-step performance evaluation process, starting with the establishment of a performance evaluation plan and concluding with continuous monitoring and updates. The committee listed scientific validity, analytical performance and clinical performance as the three essential pillars of performance evaluation.
 
Elsewhere in the guidance, MDCG provides more details about each of the essential pillars, stating that scientific validity should be demonstrated and documented for each device and explaining what that means in practice for IVD developers.
 
MDCG Guidance
 
European Commission updates Q&A on the Clinical Trials Regulation
 
The European Commission has updated a question-and-answer document on the recent Clinical Trials Regulation (CTR). The Q&A features more than 10 new questions and updates to even more existing queries.
 
New questions include how to proceed when there are discrepancies between CTR and International Council for Harmonisation (ICH) good clinical practice guidance. In response, EU officials said CTR takes precedence over conflicting rules, including the ICH guidance. Documents that are not “foreseen” by CTR, such as the progress report in the ICH E.6 guidance, “shall not be requested or submitted based on recommendations in different guidelines.”
 
The Commission also made extensive updates to a selection on informed consent and other “substantial requirements” for conducting clinical trials. Across a series of new answers, EU officials explained how the rules apply to studies conducted in emergency situations.
 
“In situations when the subject dies before any informed consent has been provided, and the data already gathered has been collected in agreement with Article 35, the data should remain in the trial. In situations when the subject or his/her legally designated representative do not consent but instead disagree with continued trial participation, no further research data can be collected,” the Q&A states.
 
Commission Q&A
 
Legislation strengthening EMA’s crisis preparedness powers comes into force
 
The European Union has adopted legislation to strengthen the European Medicines Agency’s (EMA) role in crisis preparedness and management. EMA is gaining powers to coordinate a European Union-level response to public health emergencies.
 
The new regulation came into force upon its publication in the Official Journal of the EU at the start of the week and will largely become applicable on 1 March. The exceptions are the provisions on shortages of critical medical devices, which will apply as of February 2023. Holding back the shortages provisions is part of the staggered implementation of that key part of the regulation.
 
EMA has until early 2025 to set up, maintain and manage a European Shortages Monitoring Platform. The platform will enable EMA to collect data from companies and member states on shortages, supply and demand of critical medicines.
 
EMA Notice
 
Pfizer’s oral COVID antiviral leads latest crop of positive CHMP opinions
 
The Committee for Medicinal Products for Human Use (CHMP) has recommended Pfizer’s oral COVID-19 antiviral Paxlovid and six other medicines for approval at its January meeting.
 
With the European Commission moving quickly to grant conditional marketing authorization, Paxlovid is now authorized for use across the EU. The authorization makes Paxlovid the first oral antiviral treatment for COVID-19 to come to market in the region. CHMP based its positive opinion on a study linking the drug to a reduction in hospitalizations and deaths in patients at risk of developing severe COVID-19.
 
The committee also issued a positive opinion about Breyanzi, a CD19-directed CAR-T cell therapy from Bristol Myers Squibb. CHMP voiced support for the use of the cell therapy in some lymphoma patients.
 
Two of the other positive opinions involved biosimilars. CHMP recommended the approval of Accord Healthcare’s Sondelbay, a copy of Eli Lilly's Forsteo, in the treatment of osteoporosis, and Fresenius Kabi’s Stimufend, a copy of Amgen’s Neulasta, in the treatment of side effects from chemotherapy.
 
EMA Notice, More

 

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