XVII. Expertengespräch

29 April 2022

FRANKFURT AM MAIN, GERMANY

XVII Interdisciplinary Expert Workshop “Successful Drug Development under Cost Constraints and Complex Regulations”

Proceedings of the “XVII. Expertengespräch” in Frankfurt am Main, organized by SanaClis

SanaClis proudly shares the summary report of an inspiring educational event held at the FiZ, Frankfurter Innovationszentrum Biotechnologie, on 29 April 2022. It was the first face-to-face interdisciplinary experttalk of this series of annual meetings after two online conferences due to the COVID-19 pandemic, and a 14-year long history of face-to-face meetings before.

This annual workshop brings together experts of all disciplines required to set up interdisciplinary teams for the planning, initiation, conduct, and successful finalization of clinical development projects.

This year’s event discussion revolved around the devastating war in Ukraine, the challenges and how to best deal with the COVID-19 pandemic, and the evolution of clinical trial methodology and tools, all at least to some extent impacted by the most recent geopolitical and healthcare challenges.

Dr. med. Johanna Schenk, FFPM GFMD, Company Officer and Executive Consultant SanaClis DE GmbH, had the pleasure of welcoming five expert speakers and a highly vibrant audience that contributed tremendously to a lively meeting with plenty of comments and questions in the traditionally extensive discussion part of the meeting.

I – Impact of the War in Ukraine on Clinical Trials in Ukraine, Russia, and Europe

Alexander Fetkovsky, Chief Executive Officer of SanaClis s.r.o., a mid-size global CRO with a strong operational presence in Central & Eastern Europe, outlined as first speaker the pre-war contributions of Russia and Ukraine to global clinical research productivity, the current implications on clinical trial conduct, and expectations for the future when peace will have returned:

-      There is a joint moral obligation towards patients who have already been enrolled into studies in both Ukraine and Russia pre-war. The utmost has to be done so that they can continue on study treatment.

-      Major operational challenges caused by hindrances for importation and transportation of study drugs, devices, and other clinical trial materials, organizational and regulatory uncertainties relating to patients who fled to EU countries or moved to safer Ukranian regions have to be managed well.

-      Majority of the Ukranian sites resumed their work and appreciate the possibility to work on clinical trials. COVID-19 and the war cause a lack of regular diagnostics and treatment resulting in an even higher motivation of Ukrainian patients and sites to participate in clinical trials than already observed prior to the war.

-      There is a post-war potential for Ukraine to absorb 20-30 % of clinical trial capacity that is expected to be lost in Russia.

Full presentation available here.

II – Big Data and Clinical Research – Concrete Application in Screening and Feasibility

Dr. med. Matthias Klüglich, Directeur Recherche Clinique, Boehringer Ingelheim France, focused in his contribution on the value of big data in clinical study planning, particularly screening for suitable patient populations in countries that are in line with corporate strategic considerations, ie, decision for countries where it is feasible to be involved in study conduct, and reliable timeline planning.

“Big data is where parallel computing tools are needed to handle data”, as defined by Charles Fox in 2018 was the starting point of Dr. Klüglich’s presentation for a common understanding. Examples of data sources from registries in various therapeutic areas reflected impressive numbers of patient numbers, patient visits, contributing physicians, number of practices with or without clinical trial experience that can be drawn from for clinical trial planning.

Data-based study planning leads to patient enrollment by time as planned in the right countries of strategic interest, and, in consequence, lower total study costs when compared to the traditional screening and feasibility approach, most typically ending up in longer than planned study durations, concluded Dr. Klüglich.

Full presentation available here.

III – Decentralised Clinical Trials (DCTs)– Current Status Analysis

Dr. Ralf Oxenfarth, Senior Director Business Development, Medable Inc., gave a comprehensive overview of the current status of adoption of DCTs that was and is still highly impacted by the COVID-19 pandemic. DCTs do have a large number of advantages, not the least for study participants due to fewer time-consuming visits to the investigator site but raise also particular concerns, not being able to detect safety signals early enough being a major one.

The complexity of the platform technology, the multitude of regulations, guidances, and standards have to be taken in account but have so far proven to be manageable. The acceptance or non-acceptance of Patient Informed Consent via electronic routes, so-called eConsent, requires special considerations in the planning for the conduct of multinational trials.

What the future will hold, when neither a pandemic nor a war impact on traditional clinical trial conduct routines remains to be seen. Both Dr. Oxenfarth and the audience believe that there are good arguments for DCT studies, particularly hybrid ones that contain a more balanced mix of centralized and decentralized elements.

Full presentation available here.

IV – RCT in Patients with Rare Diseases – Mission (Im)possible?

Dr. med. univ. Manuela Bamberger, Consultant Value & Access Strategy, IGES Institut GmbH, referred in her speech to the increasing need for Randomized Controlled Trials (RCTs) in small patient populations. IQWIG, the German Health Technology Assessment (HTA) institution, has a strong preference for RCTs. Nonetheless, in the international context the valid and important question remains whether there are not acceptable alternatives for dealing with the extremely limited availability of patients for RCTs.

In consequence, Dr. Bamberger raised the question whether the use of “Real-World Evidence” wouldn’t be a solution, patient-level data of high quality, comparable patient populations and outcome parameters being prerequisites.

A requirement would be that hard end points are available for operationalization comparable to clinical trials, and data on clinical symptoms and Quality of Life would be captured in routine care.

Single-arm clinical trials with external controls are better than those without control arms, are, however, admittedly not equivalent to RCTs. “Real-World Data” are, unfortunately, also limited in the treatment of rare diseases, ie, not available to the extent necessary.

Full presentation available here.

V – Quality by Design and Study Protocols: Are AI and Standards Problem-Solving Tools?

Beat E. Widler, PhD ETH-Z, Managing Partner, Widler & Schiemann Ltd., described the „State of the Non-Art”, with an incredibly low fraction of clinical trial protocols that were correct and complete. Common recruitment, randomization, and treatment errors occur in phase III trials as does an average of 3.5 substantial protocol amendments, 40 % of those being implemented prior to enrollment of the first study patient. Almost 50 % of substantial protocol amendments seem to be avoidable by a better protocol design.

The power of data has to be harnessed to run faster, cheaper and smarter clinical trials. Dr. Widler outlined how the utilization of Artificial Intelligence (AI) and Machine Learning (ML) technologies enables data mining of historical studies for identification of potential roadblocks in similar clinical trial protocols, or for getting assurance that the protocol design is “mainstream” – in the positive sense of the word.

The Risk Scope is to be defined in a Multiple Risk Analysis. Dr. Widler elucidated the elements of both a macro and nano (micro) risk analysis in real-case studies.

Finally, he addressed tomorrow’s vision of standard protocols, i.e., one protocol for one indication and one population, however, applicable to multiple Investigational Medicinal Products (IMPs) as already reality in the NIH Alzheimer’s research program.

Full presentation available here.

SanaClis gratefully acknowledges the contributions of each speaker and expert in the audience to a meaningful exchange of their experience and expectations regarding essential future elements of  successful clinical development of medicinal products and medical devices under cost constraints and complex regulations. Time will tell how many will be adopted to which extent and how soon.

The plan is to continue with this series of annual events in Frankfurt am Main on 28 April 2023.