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David Nickerson, head of clinical quality management at EMD Serono, executive sponsor of TransCelerate's ICH E6(R3) Initiative & PhRMA topic lead on the ICH E6(R3) Expert Working Group; and Arlene Lee, director of product management, data quality & risk management solutions at Medidata, and ACRO member participating in the ICH E6(R3) Initiative with TransCelerate, discuss:

Industry collaboration through TransCelerate and ACRO's partnership 

Tools to help stakeholders better understand the latest GCP guidelines

Their own recommendations for best practices in risk management and data governance

Podcasts

In this episode of the Applied Clinical Trials Podcast, David Nickerson, head of clinical quality management at EMD Serono; and Arlene Lee, director of product management, data quality & risk management solutions at Medidata, discuss the newest ICH E6(R3) GCP guidelines as well as how TransCelerate and ACRO have partnered to help stakeholders better acclimate to these guidelines.

Unifying Industry to Better Understand GCP Guidance

As clinical trials become more complex, success depends on early collaboration, thoughtful protocol design, and practical strategies to manage risk, reduce delays, and support patients.

Navigating Complexity: Strategies to Accelerate Modern Clinical Trials

Clinical trial failure insurance is turning biotech’s most costly risk into a manageable asset, opening new pathways for funding and innovation.

Clinical Trial Failure Isn’t an Inevitable Risk—It’s Insurable and Opening the Door to New Investors

Exploring stat-based testing for variables that identify deliberate data manipulation in clinical trials.


Detecting Fraud in Clinical Trials Using Statistical Data Monitoring 

While randomization is required by regulatory bodies, it is up to the sponsor on how to conduct it.

Clinical Trial Monitoring: Should Randomization Be Included?

An increase in protocol complexity is paving the way for machine learning models to optimize trial design.

Clinical Trial Failure: A Data-Driven Perspective on Risk Mitigation

In this video interview, Kate Gallin Heffernan, life sciences attorney at Epstein Becker Green, advises clinical research teams to closely scrutinize federal fund certifications and document good-faith compliance efforts, even when policies stem from nonbinding executive orders.

Performing Risk Assessments Amid Shifting Federal Guidelines

, Kate Gallin Heffernan, life sciences attorney, Epstein Becker Green, discussed the challenges clinical research teams face with compliance due to evolving executive orders and federal funding policies. She highlighted the confusion and increased scrutiny on research projects, particularly those involving diverse populations. Practical risks include potential legal scrutiny and funding agency actions. Heffernan also emphasized the importance of accurate reporting and careful documentation to avoid false claims. Future-proofing compliance involves thorough portfolio assessments, diversifying funding sources, and strengthening partnerships between academia and industry to support early-stage research and innovation.

ACT: How can research teams perform meaningful risk assessments to ensure feasibility before applying for or drawing down federal funds?

Like the reporting on past aims and progress reports on diversity aims, this has been another area where we've had clients really struggling, in part because everyone right now is obviously doing what they can to ensure that they remain eligible for as much of their federal funding as possible. The motivation is to make the certification in order to be able to draw down the funds. However, it is really important that organizations are looking at those certifications really carefully, that they are taking whatever reasonable, good faith effort steps they can to make sure that they are accurately representing that certification. We've seen a lot of different scopes of certification, so sometimes it's limited to the funds that are actually being drawn down in that no particular moment, and it relates to whether or not the funds themselves are being used to further aims that are not aligned with the government's priorities. That's an easier diligence thing, obviously, because you're looking at just whether or not that project itself has any elements that might cause concern with respect to the stated policies of the funding agency and the administration. I think the harder ones are the ones that ask you to represent what you've sort of done, everything you can to make sure that your entire program at the organization is in line with the executive orders, which again, begs the question, they're not laws. Essentially you're getting a backdoor certification to compliance with something that's not a binding law. I think that's deeply troubling to me as a lawyer in terms of a process for implementing that type of requirement, but what we've said as a practical measure for clients is do your best to make sure you're documenting all the efforts that your organization is taking across the board to evaluate its programs and to make sure that it is compliant with the law, and make sure that those efforts have been undertaken and fairly documented, so that you have something to stand on if it's challenged.

Videos

In this video interview, Rob Jones, product manager, TMF practice area, Pharmalex, shares his key takeaways from Cencora’s recent TMF Leadership Summit and touches on the importance of oversight when working with outside stakeholders. 

The Importance of Clinical Trial Oversight when Outsourcing

, Rob Jones, product manager, TMF practice area, Pharmalex, discussed challenges in the trial master file (TMF) space, highlighting outdated regulations such as ICH E6(R3). When it comes to innovation and compliance in the space, he stressed the importance of a risk-based approach, focusing on critical records and leveraging artificial intelligence for big data analysis. Moving forward, Jones believes the TMF community's collaborative nature can be viewed as a strength in navigating regulatory changes and technological advancements.

ACT: Cencora’s TMF Leadership Summit was just a few weeks ago. What were some key discussion points or trends that emerged from conversations there?

It was really good. Again, this is going back to my point about everyone being open and sharing, this was the nice thing. It was a group of us just being brutally honest about the struggles that we all face. There was one word that came up time and time again, and that word is oversight. It's something that has been in our industry for a long time. It's something that the regulation is now putting more pressure on, and it's also a word that I love, because, like many words in the English language, it has two meanings. One meaning is to oversee something, make sure it goes well, and the other is you miss something, and something bad happens. It produces this fantastic sentence that, again, in a lot of my talks, I like to bring it up on the screen, which is, “Without oversight, you risk an oversight.” It really says a lot that, again, in the past, oversight was just this idea of it's a tick-boxing exercise, but we're outsourcing more and more now. We're outsourcing to vendors, to partners, to just third-party groups in general. It's not always cost effective to do everything yourself in-house, and you don't always have the experience in-house, you can't have an A-team for everything you do. This idea of outsourcing is becoming bigger and bigger now the current regulations have really set that up as to what they expect, and in essence, what they're saying is just because you're not behind the wheel of the car at that moment doesn't mean that you should not be in control. You should be in control. You should be ready to correct when things go wrong. What we're having to do is really look at that support, really looking at making sure that it doesn't matter if it is, and this was part of what came up. It doesn't matter if it's a live trial that you're running today, and you're halfway through it, you've got loads of metrics, you still need oversight. It doesn't matter if you are getting to the end of the trial and you're about to receive it from a CRO partner. It doesn't matter if it's a trial that you never did, but your company has acquired that trial and that product, you need to prove oversight, and it's a real delicate balance, going too far one way, you're basically just doing the job that you outsourced, you're checking on everything, you're chasing people up, you're making sure that everything goes exactly as you think it should, and there was no point in outsourcing it, you've overstepped it. On the other side, what you don't want to do is just ignore it, and then when disaster does strike, if you're lucky, you know about it, but a lot of the time you don't even know that disaster struck you. You're oblivious to it, and unfortunately, regulators won't accept innocence. They will accuse you of ignorance at that point, so getting that balance and what we say a lot, is that idea of trust but verify, so when you're thinking about oversight, really think about what sort of checks you're doing. You don't want to do all of them, but how about a sample? You want to set your vendors up for success. You want to share ideas with them, and if you see something going wrong, don't wait for them to tell you, go to them, so have that two-way communication. There is no us in them, everybody's working towards the same goal, and yeah, that ultimately, over those two days that we had at our leadership summit, every talk, at some point, touched on oversight, and again, didn't matter what it was, oversight was still the thing that came in, and I think that's an area that again, as we move forward, as we think about what's happening and what's changing, it's going to become pivotal, especially when you're sat in front of that inspector and they say, “So, what did you do to make sure that this went well?”

Vendor Strategy & Collaboration

In this video interview, Rob Jones, product manager, TMF practice area, Pharmalex, discusses how risk-based approaches must be prioritized amidst the increased demand for quality and compliance. 

Embracing Risk-Based Approaches with Clinical Trial Oversight

ACT: What should leaders in the TMF space be focused on the most in navigating the increased demand for quality and compliance?

There is a quote that anyone who's ever listened to any of my talks or webinars or blogs or anything. I love this quote, and it's in ICH E8(R1), I've got it written down here. “Perfection in every aspect of activity is rarely achievable, or can only be achieved by use of resources that are out of proportion to the benefit obtained.” Sounds like a Taylor Swift lyric, but realistically, what it's saying is, in order to get perfection, you're going to have to put in far more effort than it's worth, so focus where the focus needs to be. Not all records in your TMF are equal. They're not. A protocol amendment changing the fundamental part of your study because of an endpoint is far more important than the routine chit chat that you have and meeting minutes you kicked out. There's more risk at a high enrolling site that's got 1,000 patients, than there are at another site that's got one, so focusing on where the risk is and really embracing this idea of a risk-based approach, I think that's where we need to focus on. That's where we can really get to this new demand for quality and compliance and being able to say the rest is good enough. It does exactly what we need it to do. It's fit for purpose. The other thing with risk, though, we always need to remember is, I've seen people in the past use risk-based as a way to justify doing less. I think the thing we need to remember is, risk goes both ways. There's some times where the risk drops, and you can say, “Brilliant. Don't need to do as much work as I was doing yesterday. All my metrics are green. I've got everything that I need to. I've just had a call with the rest of the study team. Everything's flying through. Brilliant.” There's other times, though, when you have a bad week and the number's aren’t looking great, and at those times, you have to do more work than you thought, but balancing that being available and being able to pivot where needed, that's really what the leaders in this space need to do. I think again, going back to the AI, this idea of there's people who can really have a first mover advantage. Going to be the same here. There's going to be people who really embrace this and really make a difference to their organization, and there's going to be other people who say, “It's too risky. I don’t want to, and I'm going to check everything twice, just to be safe.” That, to me, is where really the leadership is going to be focused, and again, where quality, compliance, cost, everything that comes into it can really be tackled head on.

In this video interview, Rob Jones, product manager, TMF practice area, Pharmalex, highlights recent ICH guidelines and how risk should be an area of focus as trial designs continue to get more complex.

Understanding the True Meaning of Risk in Clinical Trial Operations

 I mentioned, not only have we got these new regulations, but things are changing at a rate that we've never seen before, we can't keep up with. There was a time back in the 2010s where it felt like there was new things happening all the time with, again, bringing in a real foundational level smartphones and tablets and suddenly, internet everywhere, but we're even past that now, it's moving even faster. I think the thing is, if you look at things like ICH E8(R1) that was released the other year, that was almost like a foundation for ICH E6(R3), and it really talked about quality by design. It really talked about thinking about the holistic and bigger picture. They talk in there that if you're thinking about going to certain countries, don't wait until further on down the line, just incorporate those countries into the trials you're doing. That means that trials are going to become more complicated. Complication brings cost, and fast and complicated bring risk. There's no getting around that. Risk is a big, big thing, but again, ICH E8(R1) really built in the idea of quality by design and risk being a big part of that. ICH E6(R3) also talks a lot about risk. I think the thing that we should be focusing on from a leadership point of view, is really understanding that word, risk-based has been a buzzword for as long as I've been around in the scene. We've talked about risk-based, we've talked about these different approaches, but I think it's time for us to really think what that means. Risk inherently means the potential of something bad happening. It's our job to understand that and do what we can to minimize it. In the past, terms like fit-for-purpose, good enough, they're almost dirty words. They were sins. “Good enough isn't enough.” Actually, it is now, that is enough.

In this video interview, Thierry Escudier, portfolio lead, Pistoia Alliance, talks the current landscape of sustainability in clinical trials and how stakeholders are beginning to pay more attention to carbon footprint amid increasing protocol complexity. 

A New Era for Sustainability in Clinical Research

, Theirry Escudier, Portfolio Lead, Pistoia Alliance, discussed the alliance’s newest initiative to assess the carbon footprint of clinical trials. The initiative aims to answer whether decentralized clinical trials positively or negatively impact carbon footprints. Escudier also discussed how clinical research stakeholders are slowly beginning to adopt more sustainability practices, focusing on reducing waste and costs.

ACT: In terms of sustainability, how have clinical research stakeholders been responding to challenges such as operational costs?

Except a few, let's say, front-edge companies, that have already looked to that domain for a couple of years, I guess most of the clinical leaders have never really considered the sustainability, because I think no one has really assessed in the past, in fact, the impact of the clinical trial implementation. Everyone is focused for decades about ethics, about safety, about regulatory compliance, keeping I would say those trials within the budget, within the timelines, make sure that patients will, I would say, accept to be part of those clinical trials, having good data, good quality, so all those things with an increasing complexity of the trials, this has been proven many times by those studies from Tufts, it's clear that the protocols are becoming more and more complex. There is more and more, I would say, demand on both the investigator side and on both the patient and everyone was focused on that, and it's only in the recent days that there was a new mindset that is appearing to say also, well, clinical trials are not equal to zero in terms of carbon footprint, and because this is an overall action and implementation, can we reduce that impact that now people are also looking and a couple of comments is, is not to oppose, I would say, the sustainability versus the cost, because, if you think also in a different manner, one of the other issues in clinical trials is the waste, waste of packaging, waste of blood samples that are not used and even they are sent to the site, some waste of the drugs even now with all the IRT system, you can really more control, I would say, the number of supplies you are sending, but still, there is a lot of waste and this waste is purely, I would say, carbon footprint, but also it's a waste of money.

In this video interview, Vera Pomerantseva, director of product management, RBQM, eClinical Solutions, talks FDA’s latest protocol deviation guidance and potential changes to the draft.   

Potential Updates to FDA’s Protocol Deviations Guidance

, Vera Pomerantseva, director of product management, RBQM, eClinical Solutions, discussed FDA's recent guidance on protocol deviations and its impact on clinical trial management. She highlighted the importance of quality by design (QbD) and critical to quality (CTQ) factors in reducing protocol deviations. Pomerantseva views this guidance as an official acknowledgment of existing practices and an opportunity for improvement.

ACT: How do you think FDA’s protocol deviations (PDs) guidance will affect the industry moving forward into the future?

I see it as a great first step in acknowledging the complexity of this process and providing more clarity to the industry, and therefore, I hope that all the industry professionals will take advantage of the opportunity to provide comments. I actually reviewed some comments a couple of days ago. There is not too many, so I would envision that we could collaborate much better on helping ourselves to have a more consistent and more concise document.

I would definitely expect more details in the guidance, and then it's going to evolve over time, but again, I'm a now person, let's see what we can do now, not waiting for another revision since we have the chance. For example, I would expect more guidance on a couple things, and I'm going to be very specific or what I haven't seen there, but I would want to. Serious breaches: at what point should important PDs be assessed for being serious breaches, if it should be assessed, and what role should be involved? Maybe it should reference a dedicated serious breaches guidance, but I haven't seen anything in there. Governance, metrics, and escalation: it is a big topic in ICH E6(R3), but I have not seen anything on this topic in the protocol deviation guidance.

In this video interview, Vera Pomerantseva, director of product management, RBQM, eClinical Solutions, discusses the importance of open dialogue during risk assessments. 

Strategies for Embedding Protocol Flexibility 

ACT: What are some strategies that stakeholders can use for embedding protocol flexibility during risk assessments?

The strategy to embed flexibility, I think, should be an essential part of protocol design and risk assessment. This is the one of the key QBD activities, so a cross-functional team must be involved and an environment which fosters open dialogue should be created. We call it quality culture. Again, I know it's easier to say than to create it, and by the way, in 2022, MHRA issued a guidance clarifying lots of questions about the protocol risk assessment and monitoring oversight and I think they did an excellent job outlining the roles to be involved in the protocol risk assessment and basically how it should be done. The protocol should be reviewed by this cross-functional team to assess it from the different angles looking at the complexity, the burdens, unjustified restrictions, and maybe as an example, here are some questions which can be discussed by this team during their meetings, so what requirements can be less restrictive? Is everything that is in the protocol scientifically justified. Do we really need all these assessments in this protocol, and if we need them, do we need them in this particular format and with that particular frequency? How flexible should your visit windows be? Again, if you decided it's going to be plus/minus days without the need, you just created a problem for yourself, you're going to have a lot of protocol deviations. Do they really impact anything? Maybe not. It's, again, quality by design thinking.

Strategies for Embedding Protocol Flexibility

In this video interview, Dominique Demolle, CEO of Cognivia, discusses how understanding the patient journey from the very beginning of a study can help mitigate risk and improve patient centricity. 

Best Practices for Reducing Risk Upfront in a Clinical Trial

, Dominique Demolle, CEO of Cognivia, discussed challenges in improving patient adherence in clinical trials. She highlighted the reliability of adherence tracking methods, such as pill counts and ingestible sensors, and the need for tailored patient engagement strategies. Some potential solutions to these challenges include the use of artificial intelligence and designing more patient-centric studies.

ACT: What are some best practices sponsors can use to make their trials more patient-centric and mitigate risk even further upfront?

I think that most of them are doing what I'm going to say, and hopefully I would say and repeat, proactive thinking in terms of patient engagement. There has been in the US and Europe a great initiative like the CTTI in the US, or PARADIGM in Europe about providing some guidance about patient engagement. Clearly, from the very beginning of the protocol development, but up to and including the survey at the end about the patient experience is something that is definitely going to help, and as I mentioned, even more now that we are going to embrace an even larger diversity of patients, so for sure, patient engagement is a must. The second thing is, yes, but. Not everything fits all, so the more we are going to be able to tailor the support that we are going to provide to a patient, the more successful we will be. We have mentioned AI and machine learning that could be a complementary strategy to tactics and solutions that are already put in place, but really to ensure a higher probability for those patients to remain engaged and understand why they take the drug and understand why it is important and why it could be beneficial for them. Proactive thinking, integrated strategy, and taking the best of each solution to really map and try to tackle the problem.

Future of RBQM

ACT: What key takeaways do you hope to share with industry leaders at SCOPE 2025, and how do you see Cluepoints shaping the future of RBQM?

I think RBQM is becoming a much bigger opportunity. It's really about treating data as an entire ecosystem. It's not just individual data points now, it's the totality. It's about looking at patients, looking across patients, looking across studies, and data is the common element of that. For us, as we s we talk to different partners, customers, sponsors, it's really coming down to four pillars. Are you cost motivated? Are you time motivated? Are you resource motivated, or are you quality motivated? And everyone wants to say the politically correct answer, well, it's all four, but it can't be all four. You have to pick one. I’m not saying you sacrifice the others. What I'm saying is you're going to pick your priorities, and what we’re here to talk about is the fact that we are fueling all four.

 At SCOPE this year, the key objective is to advance the conversation around risk-based quality management (RBQM), transitioning it from a theoretical concept to an actionable reality. The conference provides a collaborative platform to discuss the evolution of RBQM, particularly in light of emerging technologies like AI, which were not even part of the industry's vocabulary a decade ago. The goal is to validate and expand discussions, ensuring that RBQM is implemented effectively across clinical trials.

A significant regulatory shift impacting RBQM is the imminent release of the updated ICH GCP E6(R3) guidelines. These changes are expected to transform how sponsors approach RBQM, potentially even redefining the concept of “risk” itself. Rather than being viewed as a negative factor, risk management could shift toward a more data-driven, informed decision-making process. These guidelines will influence aspects such as chain of custody and the integration of modern methodologies into trial management.

The future of RBQM is increasingly centered around data as a comprehensive ecosystem rather than isolated data points. Industry stakeholders are prioritizing different drivers—cost, time, resources, or quality—in their approach to RBQM. While all four factors are important, organizations must determine their primary focus to optimize decision-making. The industry is working toward a model where these priorities can be balanced more effectively, ensuring that clinical trials remain patient-centric while also meeting regulatory and operational goals.

Ultimately, SCOPE serves as a critical venue for shaping the future of RBQM, fostering discussions that drive innovation and efficiency in clinical research.

In an interview with Applied Clinical Trials Associate Editor Don Tracy, Richard Young, chief strategy officer, Cluepoints, offers his key takeaways from this year's SCOPE Summit in Orlando. 

Latest Conference Coverage

SCOPE Summit 2025: Richard Young Discusses Key Takeaways and the Future of RBQM

CluePoints Risk Detection

ACT: What are CluePoints’ key objectives for participating in SCOPE 2025, and how do you see the conference shaping the conversation around risk-based quality management?

I think the very first thing is we're delighted to be here, because there's a need to validate the conversation. 12 years ago, a word that didn’t exist in our vocabulary—nor did AI, to be honest. Now it’s front and center. We’re here really to continue that dialogue, to share and expand, but also transition from the potential to the reality. This is what we're doing today, this is what we’re going to do tomorrow. I think that’s the exciting thing about meeting like this, it’s not a false environment, it's a genuine collaborative environment with so many different conversations, and it's nice to be at the center of it.

ACT: How has CluePoints’ approach to risk detection and mitigation evolved in response to the increasing complexity of global clinical trials?

We’re about to live through the ICH GCP E6(R3) release. In fact, we’re hosting a meeting with the FDA in just about five weeks’ time to go over it. It's going to completely change our approach. I actually think one of the biggest outcomes will be to challenge the use of that word risk. It's a word that confuses, and I wonder whether we might move into more of an informed or a data-driven era where risk isn't a negative word, it's a really positive phrase. But those guidelines are going to change everything from chain of custody to the approach we take, to just embedding a transformational, modern methodology into every decision we make.

At SCOPE this year, the key objective is to advance the conversation around risk-based quality management (RBQM), transitioning it from a theoretical concept to an actionable reality. The conference provides a collaborative platform to discuss the evolution of RBQM, particularly in light of emerging technologies like AI, which were not even part of the industry's vocabulary a decade ago. The goal is to validate and expand discussions, ensuring that RBQM is implemented effectively across clinical trials.

In an interview with Applied Clinical Trials Associate Editor Don Tracy, Richard Young, chief strategy officer, CluePoints, discusses goals of the SCOPE Summit and CluePoints' evolving approach to risk detection. 

Risk-Based Monitoring

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