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1rem

Moving towards the development of mature quality management systems.

Site QMS-Based Site Monitoring:  The New Frontier for Clinical Research Excellence

Final guidance suggests sponsors select two doses for Phase II trials with additional data requirements. 

Revolutionizing Oncology: Insights on the FDA’s Project Optimus and Dose Optimization

Session provides insight as to how to boost interoperability and expand the middleware on a global scale.

DPHARM 2024: eSource EHR Requirements

The promise and acceptance of using this AI tool in drug development is growing.

A New Regulatory Road in Clinical Trials: Digital Twins

Compliance with diverse clinical trial payment and data standards requires specialized skills.

Bridging Patient Support Gaps While Navigating Global Regulations

In this video interview, Mark Melton, vice president of biospecimen data and operations, Slope, highlights the clinical research industry’s need for more regulation around collecting data.

Creating a Global Standard for Data Sources

, Mark Melton, vice president of biospecimen data and operations, Slope, discussed navigating data challenges in clinical trials, emphasizing the need for understanding complex data sources and ensuring a proper chain of custody for samples. Melton highlighted the importance of data mapping to standardize reporting across different labs and the necessity of secure data transfer to protect patient privacy.

A transcript of Melton’s conversation with ACT can be found below.

ACT: How can sponsors better navigate some of the current data challenges in clinical trials?

 If there was one area I would challenge the industry in, it’s ensuring that as quickly as possible, that we have the ability to, number one, establish a chain of custody, but number two is also, how do we ensure inside that chain of custody that the data that's being reported out before the sample is ever tested to give a result for whatever that assay or test may be, so all the data leading up to that is accurate. Right now, the biggest challenge in the industry is the fact that with these different data sources, they have different databases that report differently. Imagine you have six labs that speak different languages. How do you translate that? There's a concept called data mapping where you ingest that data, you map it to a common language, and then you're able to compare it. I think that's the biggest area that we have to regulate. We have to ensure that regulators are recognizing this problem, like the FDA, EMA, or whatever other governing bodies throughout the world, that ensures a standard, and right now we don't have a standard.

Videos

In this video interview, Rebecca Metcalfe, principal scientist, patient-centered research, Core Clinical Sciences, highlights the consequences of focusing solely on enrollment targets.

Addressing Limited Engagement With Underrepresented Communities in Clinical Research

, Jay Park and Rebecca Metcalfe of Core Clinical Sciences discussed their recent 

titled, “Diversity Action Plans in Clinical Trials.” In addition to key takeaways from the article, Park and Metcalfe discussed the FDA's new guidance for diversity action plans in clinical trials, the role of risk-based monitoring as a tool for improving diversity, and the importance of patient-reported outcomes.

A transcript of Park and Metcalfe’s conversation with ACT can be found below.

ACT: While the FDA Diversity Action Plan guidance is a step forward, why do you feel that even with diversity quotas, trials may still have limited engagement with relevant underrepresented communities?

 That's a great question. As Jay and I mentioned earlier, really a major theme in our piece has been the need for system change and accountability for that change, and specifically measuring how clinical trials are done, and not just who participates in them. The goal of these recent initiatives by the FDA is twofold. On the one hand, they support the generation of evidence that better reflects the population of patients that may be eligible for a given treatment, so that's a scientific good. On the other hand, these initiatives support relationship and trust building with historically marginalized and excluded communities, many of which have been exploited by medical research in the past, and that's a good for the fabric of our society. Focusing just on the numbers by using enrollment targets will address the first goal, but not really address the second goal, so in this article, we advocate for process measurements that are designed in collaboration with relevant underrepresented communities to make sure that what matters to community members about how research is done is identified, and then through monitoring, we can make sure researchers are accountable for supporting inclusive processes throughout trials. A key component of this at the system-level is making sure that underrepresented communities don't just participate in clinical research, but they really lead clinical research. Studies suggest that when we have concordance between investigator and participant race and ethnicity, that improves the enrollment of ethnic and racial minorities. On the other hand, we also have studies showing that female and Black individuals are underrepresented among principal investigators, so among those folks that are leading research. In addition to improving the processes actually within a given trial, we also need to think more broadly about what perpetuates these systems that led to this exclusion in the first place, and then what changes are needed at that higher level to improve representation in clinical trials in a sustainable way.

In this video interview, Jay Park, founder & scientific lead; and Rebecca Metcalfe, principal scientist, patient-centered research; both with Core Clinical Sciences, share their reactions to the FDA releasing its Diversity Action Plan Guidance.

Just the Beginning of Improving Diversity Initiatives in Clinical Trials

ACT: What was both of your initial reactions to FDA releasing the Diversity Action Plan guidance over the summer?

 Yeah, it's been really great to see the FDA, and specifically the Oncology Center for Excellence group taking the leadership on this much-needed initiative. I believe we certainly have a long ways to go, but I'm very optimistic that we'll continue to see improvements and making future studies be more representative, I'm grateful to be part of this dialog and contribute. In addition to our article that's been published in 

, we have submitted our recommendations to the FDA docket for this draft guidance as well.

 And just to add to what Jay said, I'm really appreciative that the FDA is using this iterative approach to develop the guidance. This is just the most recent draft with some substantial changes, but throughout this process, they've been integrating feedback from industry, community, patient organizations and academics, and we can really see the layers of feedback in building this latest draft guidance. I also agree with Jay that these changes are very much needed. We know that clinical trials have historically not represented the broader population, and in particular, have excluded non-white racial and ethnic communities. Given that historical context, it's really important that the work starts with those communities. We hope, though, that it's just the start, and that these changes have downstream benefits for other historically excluded and marginalized groups in the context of clinical trials, such as patients with disabilities or multiple comorbidities and individuals with diverse sexual orientations and gender identities. I also just want to make a nod to the broader impact that this guidance can have, which is really that the FDA is leading the way on improving representation in clinical trials and as a company that's based outside of the US, but does a lot of work in the US, it's exciting to see how these changes will likely ripple out into other regulatory bodies and health technology assessment agencies. This isn't just a great thing for people in the US, it's a great thing for clinical trials around the world.

In this video interview, Jay Park, founder & scientific lead; and Rebecca Metcalfe, principal scientist, patient-centered research; both with Core Clinical Sciences, discuss a recent article they authored on the guidance.

A Strategic Look at FDA’s Diversity Action Plan Guidance

ACT: Could you tell our audience a bit about your article “Diversity Action Plans in Clinical Trials” and provide an overview of some of the key themes?

 I think there are a few key themes in our piece. I'm going to touch on the one that I think is the most salient, which is this broader question of how we measure improvement and ensure accountability, and that really includes what we measure and also when we measure it. Right now, the FDA guidance is suggesting that we should use enrollment targets tied to epidemiological evidence about who is impacted by a given condition. While that's important, we don't really believe that enrollment targets alone are sufficient to measure change, because underrepresentation of specific groups in clinical trials is not something that just happened. It's really the result of complex societal processes and systems, and what that means is that in order to make meaningful change, we need to address those systems, both broadly at a societal level and then also at the trial level by making sure that trial processes are inclusive and reflect the needs and priorities of patients and communities that have been historically excluded. The focus of our piece is really about shifting how we think about measuring change in representation in clinical trials and then grounding that shift in meaningful patient engagement.

 Building on what Rebecca has said, our article is really about adding to this important initiative that's being honed by the FDA, and it's been really nice to see such an important collaboration between the FDA, industry, and other patient organizations on these diversity action plans. While we believe that this the right step forward, we can learn from other diversity initiatives outside of the clinical trials landscape. We have seen in other areas where diversity quotas have been implemented, positive changes were only achieved when there were also accountability implemented as well. Our paper intends to provide actionable recommendations with the framework for risk-based monitoring that is commonly used in clinical trials. Already central to our recommendation is what we call patient-reported process metrics. The rationale these process metrics in how patients are engaged for enrollment and how they're retained during the follow up is similar to PROs or patient-reported outcomes as a supplement to the enrollment targets we can benefit from hearing and learning from the subjective experiences that patients are involved in during their clinical trial experience, and by listening to the patients and giving them a voice, we can be more patient-centric instead of just having enrollment targets. There will be some other benefits as well. In terms of managing risk, we can assess these process metrics during the trial at the same time, we're monitoring these enrollment targets. This couldn't be an important way to modify enrollment strategy. In the unfortunate case that the trial itself is running behind, it's in diversity enrollment targets, and after the trial, we can also use these process data generated to plan for post marketing, market surveillance studies, should they become necessary, or other future studies that diversity action plans will be mandated for.

In this video interview with ACT editor Andy Studna, Mwango Kashoki, SVP, global head of regulatory strategy, Parexel, discusses how the guidance should prompt better-designed oncology trials and greater diversity. 

Future Impact of FDA’s Multiregional Clinical Trials Guidance

, Mwango Kashoki, SVP, global head of regulatory strategy, Parexel, discussed the FDA's new guidance for multiregional oncology trials, emphasizing the need for diverse patient populations in clinical trials. The guidance requires companies to proactively plan trials to ensure data applicability to the US population, considering factors like patient characteristics and healthcare systems. The expected outcome is better-designed trials with broader access and representation.

A transcript of Kahsoki’s conversation with

ACT: Looking forward, what do you think the future impact of this guidance will be?

Well, ultimately, I'm hopeful. I'm always encouraged by new guidance. I think guidance represents the progressive thought, the advancement of new ideas, the solidification of advice and experience and embeds into practice the drug development that we all are engaged in. Ultimately, I think that the guidance is going to result in even better-designed oncology, multiregional trials. I think these will be conducted in a wide range of sites and locations, and yield information that is helpful across the globe. In the US specifically, I think the most visible, maybe even the more immediate impact will be where the trials are run. We'll begin to see, as I mentioned earlier, diversification of investigators, and we're going to see a diversification of study participants. People are going to have to talk even more with one another, so the community-based healthcare providers talking about their needs, their systems, how to integrate with maybe some of the complexities that may be required for clinical trials that will need to be adapted, perhaps. Overall, it opens the door wider, I think, to oncology patients to receive investigational oncology products as a therapeutic option. Hopefully it’s better for all.

In this video interview with ACT editor Andy Studna, Mwango Kashoki, SVP, global head of regulatory strategy, Parexel, touches on challenges that may be created by the guidance such as meeting multiple regulatory requirements. 

Potential Challenges with FDA’s Multiregional Clinical Trials Guidance

ACT: What does the guidance mean for sponsors and other stakeholders involved in trial design?

I mentioned sites and regions in Africa, Latin America, and the potential relevance of populations there to the US population. There's a little bit of a what I think is a contradiction in the guidance in terms of what companies must do, so on the one hand, the FDA is saying, yes, you could consider expanding to those sites, it's going to help you with your diversity and your population. At the same time, the guidance is also saying you must ensure that wherever you were conducting the study, the standard treatment that's provided in these other regions is reflective of the US standard of care, so that now limits where you can go. I think as companies are considering broadening to what I'm terming, non-traditional regions, they may have to go to specific countries. A very commonly cited example is South Africa, in Africa as an example.

Then, as a last thought, the guidance does pose, I think, a little bit of a challenge if a company is thinking that it's multiregional trial will allow for a more streamlined approach, or more streamlined overall development program. We know that regulators in different regions have requirements for their populations. They too, want to make sure that the trials that are conducted have data that will be relevant to their regional populations, so those regulators will themselves impose region specific requirements, etc., so companies are left in this bind of, how do I meet multiple requirements? It could end up being that a company, depending on how strict the FDA and or any other regional authority is, that could end up being that companies have to do multiple trials, so a global trial, a mix of persons, but if that is not satisfactory to the FDA, then the FDA might say, actually, you need to do another study with a population that is indeed representative. This is why I believe the FDA says first, work through your plan for how you're going to ensure that you're pulling together a representative population and then make sure you talk to us very early on so that we can negotiate, liaise, guide you through that thinking.

In this video interview with ACT editor Andy Studna, Mwango Kashoki, SVP, global head of regulatory strategy, Parexel, discusses how sponsors will need to plan ahead even further for their oncology trials. 

Planning Ahead for FDA’s Multiregional Clinical Trials Guidance

Staying on the theme of diversity and ensuring diversity, it means that companies must begin to plan their global oncology programs much earlier than they probably were thinking, probably as early as Phase I, definitely before Phase III. In the oncology space, we know that companies are often seeking accelerated approval, so they might be seeking approval on a limited number of trials or Phase II study results, so it's important that their study population, even up to the phase of Phase II is appropriately representative. They've also got to be thinking about ensuring diversity of their Phase III trial populations, because the Phase III trials which are confirmatory and completed post-approval in the accelerated approval circumstance, these Phase III trials must be underway at the time of the accelerated approval decision, so companies must be proactively planning very early. How do we enroll an appropriately representative population for the US right as soon as possible in our program, if we're planning a global program?

I mentioned that the FDA is encouraging expansion of the types of sites for multiregional clinical trials. This, in turn, means that companies must think how we actually run these trials in a community-based site, just to keep that as the example, how will we collect the data? Often, these are not sites that have incorporated clinical protocol, clinical trial protocols, into their practice, so there is some learning first, but there's also the matter of data capture and especially in the community setting, you want the protocol to be as streamlined and as least burdensome as possible to the investigators as well as the patients, so thinking about, how do you incorporate the data capture that's happening as a matter of clinical care into your clinical trial protocol becomes an important consideration. It was interesting to me that very shortly, either before or after the multiregional clinical trial guidance came out, the FDA also issued a guidance called integrating randomized control trials for drug and biological products into routine clinical practice, and that provides recommendations on how to best collect data in a clinical trial such that it is reflective of routine clinical practice. I'm sure there was a lot of internal conversation within the FDA about how to tie all of the recommendations together, but I think for companies, when they are planning their global trials, thinking about their sites, they now have to think even further. How are we going to design the study of data collection so that it's easy to do in those additional sites.

In this video interview with ACT editor Andy Studna, Mwango Kashoki, SVP, global head of regulatory strategy, Parexel, highlights how FDA’s multiregional clinical trials in oncology guidance encourages more diverse site locations and patient populations.

Ensuring Greater Access and Diverse Patient Populations

ACT: How does the guidance address greater access to trials and more diverse patient populations?

I'll point out a couple of examples that stood out to me, but certainly from the very beginning, the guidance says, in order to ensure that you are developing a program that is going to be appropriately representative, you've got to look at the characteristics of the patients that you're targeting, so that includes the demographics of the populations and any unique physiologic characteristics of the target population, beyond race and ethnicity. The analysis of the target population, bakes in in the aspect of diversity of the trial populations.

A couple of things to expand on. The guidance also notes that the companies can enroll foreign participants into trials, so inclusion of sites in foreign countries where the participants would have features, characteristics that would be applicable to populations here, so if you had a site in Africa, there might be parallels that could be made to an African American population as an example, so when there is sound reason from a clinical, medical scientific perspective to make the correlations between a population that is in a foreign site versus a US site, then go ahead, include these foreign sites in your multiregional clinical trial. This expands the access of these investigational oncology products to patients beyond the traditional locations, we'll call it, and expands access to traditionally underrepresented populations.

Another important aspect that I noted in the guidance is the encouragement to diversify the clinical trial sites beyond our typical academic tertiary care center. There's mention of community-based sites, as an example. This is important because we know that that will permeate to the access of clinical trials, to a broader population who may have accessibility issues, who may want to stay with their provider, whether that's an individual person or location. It's also important because expansion to community sites expands the diversity of the investigators themselves, so now you have community-based physicians learning and employing clinical protocols into their daily clinical practice. There's a lot of data that exists already on the benefits of community-based clinical trials, I won't expand upon that there, but it's notable that the agency is saying, as well as in the oncology space, consider community-based trials.

In this video interview with ACT editor Andy Studna, Kashoki, SVP, global head of regulatory strategy discusses the new draft guidance and its emphasis on proactive planning. 

Mwango Kashoki of Parexel Shares Initial Reaction to FDA Guidance on Conducting Multiregional Clinical Trials in Oncology

ACT: What is your initial reaction to the FDA’s latest guidance on conducting multiregional clinical trials in oncology?

 I thought that the guidance actually is quite timely, and it is reflective of adding to the ongoing conversation that the agency has been having about the need to ensure that the patients in clinical trials are indeed representative of the target patient populations. We know that in 2022 there was the passage of FDORA, the Food and Drug Omnibus Reform Act and that established the requirement that companies or drug developers actively plan for how they are going to increase enrollment of underrepresented populations in clinical trials, and of course, that's for the purpose of ensuring that there's ability to assess for generalizability of the results to the target US population. Now, what this new guidance on multiregional oncology trials does, it expands upon that principle, it's basically saying that when a company has a global clinical development program, it's got to make sure that it's making plans actively to ensure that the data collected from these multiregional trials is indeed applicable to the US population. In other words, when you're designing a multiregional clinical trial, you should, as a company, consider that there’s important differences in the US population, but to the patient characteristics, disease factors, our healthcare system characteristics, etc., and these have to be taken into account during the analysis of the results and therefore the interpretation of the results. The guidance is saying, proactively plan your studies, these multiregional trials, and making sure that you're taking into full account all of the impact factors, so the timeliness of the guidance vis a vis the larger conversation that's happening around ensuring diversity of clinical trial populations was notable to me.

I also thought that it was helpful in that it's a guidance that consolidates the information that FDA has been giving to companies—more on an individual basis—in meetings to discuss the company-specific development program, their specific clinical development program, challenge, or opportunity and as the FDA has been gaining more and more experience with global trials, everyone's looking at a global development program, it seems like the agency is now in a position to consolidate its learnings and the best practices for companies, particularly for oncology trials, because those can be very rapid. They can be based on a handful of trials of certain designs, so it's important that the FDA put out this guidance in a consolidated manner to oncology drug developers so they can proactively plan, as I said earlier, and of course, to help the FDA in its regulatory decision making.

In this video interview with ACT editor Andy Studna, Kashoki, SVP, global head of regulatory strategy, discusses the new draft guidance and its emphasis on proactive planning. 

 In this video interview with ACT editor Andy Studna, Erin Erginer, director of product, Certara looks forward and shares her insights on the future of data management. 

Regulatory Outlook on Data Management

, Erin Erginer, director of product, Certara discussed the growing complexity and volume of data in clinical trials. Data is now captured from biospecimens and digital health technologies, including advanced genetic and imaging data. Regulatory agencies require standardized data submission for analysis, but do not dictate collection methods, leaving pharma companies to develop their own standards. Lack of standards leads to inefficiencies, with only 20% of studies meeting deadlines, causing significant delays and costs. Improper data collection can lead to missed endpoints and regulatory issues. Collaboration among pharma companies and external vendors is crucial for improving data standards and trial efficiency.

A transcript of Erginer’s conversation with

ACT: Looking forward, what are some actions you would like to see regulatory bodies take to address the challenges we’ve discussed?

 Well, I think that regulatory agencies have done a good job ensuring that the teams are using those submission standards and requiring that data integrity and being able to demonstrate how your workflow is going through, but I really do think that it comes down the remit of the pharma industry to be able to collaborate internally with each other and work together along with the external vendor data providers in order to create those data standards that can be used. Really solving this problem is going to mean that you are going to begin able to conduct trials more efficiently and ultimately get the drugs to the patients as they need them.

In this video interview with ACT editor Andy Studna, Erin Erginer, director of product, Certara looks forward and shares her insights on the future of data management.

Regulatory

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