Lisa Henderson, Editorial Director at Applied Clinical Trials, offers up a summary of key topics - some perennial to the industry and some new advances.
Lisa Henderson, Editorial Director at Applied Clinical Trials, offers up a summary of some of the key themes from Clinical Trials Europe - some perennial industry topics and some new advances.
Clinical Trials Europe included topics perennial to the industry, as well, advances in the industry and those, of course, related to the impacts of COVID-19. Even if perennial, discussions no matter what topic, did drift toward COVID—a natural happenstance of everyone’s experience since earlier this year. However, it does appear, that if there was an innovation a CRO, site or sponsor was experimenting with, that innovation became more widely used and, therefore, accepted during COVID. Most of these innovations center on the digital experience, whose benefits and challenges of adoption for all stakeholders have been debated for quite some time. The event was a great opportunity to bring together speakers and attendees to share those experiences, and in cases, debate further the merits further.
"The Future of Clinical Trials", a panel discussion, was heavily weighted to the technologies and practices furthered during COVID projected onto the future screen. It also set the stage for many of the hopes and barriers toward clinical trial practice that many of the presentations centered on.
Panel members including Kenneth Getz, Deputy Director and Professor, Tufts Center for the Study of Drug Development, Tufts University School of Medicine; Anita Nelsen, Senior Vice President and Head, Translational Medicine, Parexel International; Richard Stephens, National Cancer Research Institute Consumer Forum, Former Clinical Trial Participant, UK; Sheuli Porkess, Executive Director Research Medical & Innovation, Association of the British Pharmaceutical Industry (ABPI), UK; and Kai Langel, Director, Janssen Clinical Innovation (JCI), Janssen, Spain, joined Moderator Julianne Hull, CEO, WenStar Enterprizes and UK Professor to provide some future insights.
COVID-19 did bring together sponsors, CROs, sites and more together more quickly in collaborations and processes more quickly than in the past. The panel mulled if the examples of this directed toward COVID therapies could, in fact, be driven toward other therapies, and specifically toward developments of precision medicine. Langel briefed attendees on initiatives that allowed data and science to come together, supported by harmonization efforts in the shape of data standards to facilitate that on a large scale in Europe.
The problem related to data was echoed throughout the panel. Getz maintained with the growth of biomarker and genetic data used in active drugs in R&D, the need for complete and compatible data moving forward is imperative. “There is an expectation that with an open collaborative model and broader industry-wide actions to create harmonization and higher levels of compatibility are some of the key ways that that precision medicine will become more standard practice.”
From the patient perspective, Stephens noted that beyond the data harmonization issues is the data as it relates to samples and biobanking. In the UK, he described patient discussions around consenting just for that and educating patients on how and what their samples would be used for. “There are opportunities,” said Stephens, “but it applies to industry, academia, biobanking, data and helpful to see advisory groups allowing more data sharing in COVID but, as a cancer patient, I hope they do it in cancer as well because cancer is killing more people than COVID.”
With the many advances in technology used in clinical trials during COVID, and practices such as decentralized trials, and effects on patient participation, the discussion soon turned to where will industry be post-COVID?
Langel thought that once there is a taste of what collaboration is like, it will be hard to go away. He compared it to the invention of the wheel: “No, I want to carry things around and I don’t want to use the wheel.” He reiterated that as a global experiment, aspects brought forward by COVID are working out and regulators are OK with many of the changes, and, therefore, what’s successful will remain. He suggested that protocol deviations during COVID were not perfect but we can learn from that. “There will be data points that worked extremely well, and those that will show how they could improve,” Langel maintained. He also suggested that pandemic-proofing clinical trials will be a concern moving forward. Having a Plan A, Plan B with preparations including remote monitoring, telemedicine, sensors and more will be the norm. “I think people will be investing in preparedness in the future and will cause momentum and will carry on after the crisis is over,” concluded Langel
Getz admittedly offered a “somewhat cynical” perspective. “I think a lot of change in behavior in response to pandemic may be more of a short term or one-time occurrence, even though it has facilitated much more widespread use of many approaches supportive of the remote and virtual clinical trial activity,” he said. “However, if you look historically at a variety of solutions and approaches that have been applied, long-term if they are not utilized well or do not provide a consistent ROI, then we typically see organizations revert back to less than optimal behavior when it comes to a conceptually promising solution.”
Getz further said the pandemic caused the necessity to force collaborations, but without that necessity, organizations could try to simplify trial complexity and not put forth the foundations necessary to execute those models in the future.
Langel expressed that more long-term strategy would help this situation and Getz concurred that more organization-wide strategies and governance models, scaling, contracting, based on use of compatible and integrate data.
More questions revolved around specific practices of clinical trials against the COVID lens, as well as global or regional influences of those practices in such areas including precision medicine, data sharing, patient consent to samples, ICH GCP, remote monitoring, silos, eConsent, and more.
The panel event, "Ensuring a Good Recruitment Strategy - How to Successfully Recruit Patients" was moderated by Diana Sims-Silbermann, Specialist General and Emergency Medicine, Anesthesie, Senior Trial Manager, Early Development and Clinical Pharmacology, Janssen-Cilag GmbH, Johnson & Johnson, and included members Dr. Philipp Badorrek, Head of Department, Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine ITEM in Germany; Olivia Barnes, Senior Research Nurse, Sherbourne Medical Centre; Dr. Estrella García, Director Global Clinical Operations, Global Clinical Operations – R&D of Almirral in Spain, and Amelia Hursey, Research Participation Lead for Parkinson’s UK.
During the pandemic, Parkinson’s UK sourced a questionnaire that found Parkinson’s patients didn’t want to burden the healthcare system and were more likely to involve themselves in online questionnaires and surveys to help inform larger trials. With that response, Hursey says a new trial addressing hallucinations in Parkinson’s patients was re-designed with this information to minimize interactions between research and participation, dispense trial medications via mail, and opened up to a new model of ECGs. Said Hursey, “It has opened up for better future patient recruitment.”
Outside of the experiences during the pandemic, Badorrek mentioned they have moved almost completely to social media, which gets most results from an advertisement budget standpoint than local newspapers. “For Facebook in Germany, average age is 47. The social media model of pay for click is not as expensive a newspaper advertisement.” While Badorrek and García agreed that there is the potential for “trolls” or negative comments to surface in social media, a policy of constant surveillance to mitigate untrue or controversial comments with rational and friendly answers helps. In some cases, where commenting spirals, the posting should be closed and start over.
In regard to recruitment vendors, the group felt that they tend to be expensive and tend to be “enthusiastic” about their databases, however, they seem more a fit for multi-site trials. Hursey mentioned that clinical trialists shouldn’t be afraid to engage with different research groups if they want to increase the diversity of their patient pool.
Specific to the UK, the question of asking GPs to contact patients for recruitment purposes was raised. Like in the United States, the situation centers on the cost-benefit ration. Barnes noted, “It is not worth the effort for GPs to recruit their patients. It takes too much work, with a lack of remuneration.” And, as in the United States, companies have created business models to bring clinical research into the physician’s offices to make it financially sustainable.
Again, as in many areas around healthcare professionals and patients, the issue is trust. While Hursey related that as a research nurse, if a patient hasn’t shown interest within five minutes, “we just drop it because we want educated, willing, committed volunteer.”
García agreed and believes the empathy of investigator or the study staff and how they communicate information is one key to recruiting patients. “The informed consent form is large and complicated, and sometimes we need to translate more, but the investigator or study staff should share with patient and help them understand. Otherwise, if it’s not going anywhere, they have to stop. How they share it is key.”
While set against the backdrop of the most desired, most talked about, most controversial vaccine development of our time, COVID-19, a session from Professor Robert Dingwall, Professor of Sociology, Nottingham Trent University, UK centered on vaccine acceptability in all cases. Dingwall, as a social sciences expert, positions vaccine acceptability not as a scientific endeavor, but a social science one. To that end, Dingwall offers countless insights for biopharma companies along the way toward understanding how their potential vaccines might be received. While some of the questions still lie in the hands of what pharma does with any therapy, such as what providers think; what payers expect; and patient access to the medicines, the vaccine journey includes what pre-conceived biases that need to be addressed by these stakeholders. These include how vaccines are viewed in general (science vs. faith); trust in government; and moving to cultural issues including the source of the vaccine material and then how to help see negatives as a positive.
One of Dingwall’s suggestions is to start early in this understanding process so that companies can bake in a higher expectation of acceptance from the beginning. Maybe because COVID-19 doesn’t have the luxury of coming from this earlier understanding and in a globally, completely heterogenous environment, the misunderstanding is currently high. This should not preclude anyone from watching this presentation, as it is a completely neutral, and therefore, refreshing, way of viewing the process.
It was tempting to put the Brexit topic under the perennial category, but even as the Brexit process has seemingly been going on for a long time, it is advancing as per Sheuli Porkess, Executive Director Research Medical & Innovation, Association of the British Pharmaceutical Industry (ABPI), presentation “Brexit – What Impact will this have on Clinical Trials in the UK?”
As Porkess notes, the negotiations are continuing, but the ABPI requested inroads be made on some of the concerns around the status of the UK-EU; a medicines annex and mutual recognition agreement and the need for clarity around Northern Ireland. ABPI also issued this paper as updates to clinical trials in the UK.
However, many issues that can be addressed will be found in the MHRA Post-Transition information found here, which includes the import of clinical trials supplies; approval, registration and reporting of clinical trials; regulation and licensing (submissions and marketing authorization); GDPR and data adequacy; Horizon Europe & IMI; and the immigration/movement of people. According to Porkess, the UK and EU have made clear they will protect the rights of citizens working in each territory.
"Navigating the Changing Landscape for Successful Precision Medicine Development" from Angela Qu, Vice President, Translational Medicine at Parexel International was a comprehensive session that takes both a look back and look forward to precision medicine. Specifically, how we got to the current development of precision medicine under the auspices of rare disease, to cancer sub-types. Qu offers the regulatory approval and pipeline landscape of therapies using biomarkers of gene mutations, and those with companion diagnostics as part of their approvals.
Qu suggests ways that sponsor companies can use strategies such as RWE and focused protocol design. She then segues into the next wave of precision medicine, tumor agnostic drug development, and suggests it is time to rethink the genomic-driven universal space.
The panel discussion “What are the Main Challenges of AI and What Advancements Have Been Made?” included Dr. Corrette Ploem, Associate Professor, Amsterdam University Medical Centre, University of Amsterdam; Michel Arnoult, Chairman, Arnoult.org; Alexandra König, Clinical Researcher, Memory Clinic at Nice University Hospital, University of Côte d'azur, and INRIA; and Ole Dammann, CEO of KFGN with the Moderator, Deepak Bandyopadhyay, Associate Director of Quality Analytics for Janssen.
AI is a tough topic in the best of circumstances because its uses can be applied across any area of clinical trials to improve a plethora of manual processes. It is the nuances behind AI, as well as its potential uses, which contribute to its complexity. Data for non-data people is hard to wrap around, but the panel delivered on the concepts of data, the implications around machine learning, and some barriers to acceptance.
Dammann fielded the first question around current uses of AI in clinical trials: in risk-based monitoring to look for patterns, and to identify the right subjects for clinical trials. He remarked that the next set of solutions could be in finding the right dosing in trials, or potential diagnostic systems, but these areas are implicit to patient safety, therefore, more focused development.
The challenges with AI is a mixed bag of training the systems, regulatory, data privacy, validation and acceptance by clinicians and patients.
There was a robust discussion around AI’s role in regard to the clinician and the patient. Much of this centered not only on the investigator/ subject relationship, but potential decision-making within the physician/patient in the healthcare setting. The reasoned response that came out of that was emphasizing the trust placed in the clinician by the patient, and therefore understanding of how AI is used, communication on how it is used, as well as transparency in the process.
Arnot elaborated on the difficulty around training machine learning systems because the machine is learning all of the time, so it all comes down to the quality of the data. Dammann agreed, saying, “AI and machine learning requires certain prerequisites around what kind of data should be used in future, how should we structure the data? Also, how reliable are the data we are using for AI? That’s questionable. We have a high data quality in clinical research but how do we use data from former trials? This requires a mind shift from the industry. We need to share the data outside of single organizations.”
In regard to this issue of data structure and sourcing is the importance of data sharing and privacy concerns. For example, Ploem felt that the collection and clarity around the use of data is an international issue for big data research, and who is supervising that data, the access, the use all results in many questions around data protection on that international level. If there were an international governance body, Ploem believes that there could be more robust achievements with data.
Combined into the governance piece of data and AI uses, is the validation issues with a specific nod to the regulators’ role, as well the patient privacy issues, which include a higher burden on GDPR.
While many concerns surround AI, Dammann maintained that its upcoming uses become another tool in the toolbox to inform better decision-making, to free time by handling manual processes, and to ensure qualitative rigor. For example, time freed to discuss more treatment or research options with patients; detections in images or text that can be more reliable than humans can achieve; and as an assistant with administrative tasks.
Lisa Henderson is the Editorial Director at Applied Clinical Trials,
