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Clinical Data Management’s Next Evolution: From Data Stewardship to Data Intelligence

Clinical Data Management (CDM) is undergoing a fundamental transformation. What was once primarily a function focused on data collection, validation, and cleaning is now emerging as a strategic, technology-driven discipline at the heart of modern clinical research.

Today’s trials generate unprecedented volumes of complex data. A recent Tufts Center for the Study of Drug Development survey found a 7x increase in data points and 4x increase in data sources. Here at Cytel we have seen studies with over 20 data sources. Beyond traditional electronic data capture (EDC), clinical studies increasingly incorporate electronic health records (EHRs), wearable devices, mobile applications, genomics, imaging, and real-world evidence (RWE). While these data sources create enormous potential for deeper insight, they also introduce new challenges that conventional CDM approaches were never designed to handle.

To unlock the value of this expanding data universe, clinical organizations must rethink not only their tools, but also their talent, workflows, and mindset.

 

The rise of new roles in clinical data management

This evolution has created demand for new, specialized roles that bridge clinical knowledge, data science, and technology:

 

Clinical Data Scientist (CDS)

Clinical Data Scientists focus on extracting insight from complex medical data. They apply advanced analytics, visualization, and domain expertise to uncover trends, assess data quality risks, and support clinical and operational decision-making.

 

Clinical Data Engineer (CDE)

Clinical Data Engineers design and maintain the data infrastructure that makes modern analytics possible. They build robust, compliant data pipelines, integrate diverse data sources, and ensure data is reliable, traceable, and analysis-ready across the clinical trial ecosystem.

 

Together, these roles move CDM beyond data stewardship toward true data enablement.

 

The expanding complexity of clinical data

Modern clinical trials are no longer linear or siloed. Data flows continuously from multiple sources, often in near real time, and in formats that vary widely in structure, granularity, and reliability. Managing this complexity requires more than rule-based checks and manual reviews. Organizations need scalable data architecture, advanced analytics, and intelligent monitoring approaches that can adapt as data volume, velocity, and variety increase. This shift marks a move away from reactive data cleaning toward proactive data intelligence.

 

Why data visualization matters more than ever

As data points multiply, traditional listings and static reports quickly become unmanageable. Data visualization is no longer a “nice to have,” it is essential. Advanced visual analytics enable clinical teams to identify patterns, compare data across sites, and detect emerging issues early, before they compromise data quality or timelines. By transforming complex datasets into intuitive visual insights, teams can move faster, ask better questions, and focus attention where it matters most.

 

Figure 1: Early Detection of Data Quality Risks through Data Visualization Use Case

Systemic audit trail analysis and regulatory expectations

Regulatory expectations are also evolving alongside data complexity. The 2023 EMA guidance places increased emphasis on audit trail review, signaling a shift from point-in-time checks to systemic analysis. Manual audit trail reviews are no longer sufficient at scale. Instead, sponsors and CROs must adopt analytical approaches that continuously monitor audit trail activity while identifying unusual patterns. This will support site fraud detections, risk-based quality management, and inspection readiness. Analytics-driven audit trail review not only improves compliance, but it also strengthens overall data integrity and operational oversight. In short, the audit trail data needs to be treated similarly to clinical data. In 2025, Cytel was made aware of multiple sponsors being asked to provide evidence of a systematic review of the audit trail data by regulatory authorities.

 

Figure 2: Systemic Audit Trail Analysis Use Case

From comprehensive reviews to trend and outlier detection

In a world of big data, reviewing everything is neither practical nor effective. The future of data cleaning lies in intelligent prioritization. By leveraging statistical methods and trend analysis, CDMs can shift from exhaustive data review to targeted investigation focusing on outliers, inconsistencies, and meaningful deviations. This will reduce manual effort while improving data quality outcomes, aligning with risk-based monitoring principles, and enabling faster, more confident decision-making throughout the trial lifecycle. This is accomplished by statistically analyzing the data variability similar to how statistics are used to evaluate for safety and efficacy and assigning risk levels to the various checks that are performed. An overall risk level is also created and based on the analysis targeted data checks are performed.

 

Figure 3: Risk-Based Data Cleaning Use Case

Building insight-ready clinical data ecosystems

The future of clinical data management is not defined by a single tool or technology, but by an ecosystem; one that combines modern platforms, advanced analytics, and specialized talent.

Organizations that invest in insight-ready data architectures and deploy the right expertise will be better positioned to improve data quality, accelerate timelines, and generate deeper insights from increasingly complex datasets. As clinical research continues to evolve, CDM’s role is expanding from managing data to unlocking its full strategic value.

 

Interested in learning more?

William Baker and Jenn Sustin will be hosting the webinar “Enabling the Shift to Clinical Data Science and Engineering for Modern Trials” on February 18 at 10 am ET:

Looking Ahead to 2026 and Beyond: Views, News, and PHUSE

At the outset, a disclaimer. This piece is potentially “old hat” for you, as it comes from someone who has retired from executive/managerial roles. But wait! One cannot ever retire from observing, admiring, and, therefore, learning. “With all thy getting, get understanding” — a biblical verse inscribed in a Cytel founder’s office — is etched in my mind, so the insatiable quest for absorbing.

What’s in store in the year ahead and beyond? A few things come to my mind:

 

AI and even more AI

I know, I know. You have probably had an overdose on readings about AI. Still, my two cents in short bullets.

  • You gotta learn to use AI seriously. Like it or not. So, you better like it.
  • You don’t need to become an AI expert, just a skilled user.
  • Examine your job description. Anything routine/mechanical is going to evaporate with AI magic. So, amplify your focus on innovating, creating, and original thinking.
  • Don’t trust AI blindly. Find smart ways to validate what it churns out.

While AI usage is still in a nascent stage, early adopters of smart prompt engineering and dependable validation will be at a great advantage for future opportunities.

Here at Cytel we have access to a first-rate suite of AI tools. Judicious and ingenious use paves excellent career growth pathways. Go get started!

 

Domain knowledge shall reign supreme

Through my 28 years at Cytel, every occasion of learning something new about drug development brought me new opportunities. Whether it be a complex therapeutic area, or how adaptive designs are crafted, or how drug delivery works, or how DMC functions — a little bit of enlightenment went a long way in delivering greater value to a client. Regardless of one’s specialization (the “horizontal”), the domain “vertical” opens doors to career growth. I see that becoming even more prominent going forward.  For example, real-world data (RWD) is helping accelerate and enhance drug development, and I have seen young statisticians get excellent opportunities based on their deepening understanding of RWD.

 

Jack of all trades

I have been a firm believer of broader knowledge (not just deeper) working wonders. Occasionally, when I was pushed into supporting business development (e.g., crafting RFP responses, or making a pre-sales demo and presentation), the value of knowing a little bit of everything dawned bright and clear. This year and beyond in future, I feel sure versatility will be a big virtue — for value delivery to the client and, therefore, to one’s own career.

 

GCCs (Global Capability Centers) gain traction

Knowledge-focused companies like Cytel are ideally suited to become skilled competency centers serving global sponsors. The three-decade-old idea of SDFs in the Software Industry is reincarnating now through the concept of GCCs in our domain. Deep scientific knowledge, when combined with deep understanding of a specific sponsor’s processes and specialties is invaluable. “Outsourcing” began with simple cost saving as the core proposition. That has rapidly matured toward 1) tapping large talent pools; 2) innovation and intellectual property creation; and 3) specialized CoEs (Centers of Excellence). In 2026 and beyond, I foresee GCCs becoming knowledge powerhouses. And I foresee global biopharma continuing to welcome specialist service providers to host the GCCs, in addition to their own DIY versions.

 

PHUSE APAC Connect

From expressing the news and my views, let me now move on to PHUSE. This global Healthcare Data Science Community, over the past two decades, initially held annual conferences all across Europe. It then spread its wings to the US with the CSS (Computational Sciences Symposium), partnering with the US FDA, and then to the “US Connect” annual conferences.

It is now making a grand debut in the Asia Pacific Region. The first ever “APAC Connect” of PHUSE is scheduled from February 19–21 in Hyderabad, India. PHUSE has a large following in the APAC region with over 10,000 members spread across India, China, Japan, Singapore, Malaysia, Australia, and several other countries.

What’s more, this event will include the India CDISC Day 2026!!!

 

This event will address a few major themes.  

  • GCCs in the APAC region. This region has the unique advantage of a huge talent pool and is moving up from cost efficiency to innovation hubs and CoEs.
  • Impact of AI. How AI will reshape careers and leadership in drug development. This topic will figure across panel discussions, presentations, and the leadership stream.
  • There will also be a panel discussion on upcoming innovations in drug development that are going to be potential game-changers.

If you are attending the event, use the PHUSE app to curate your personalized agenda and schedule, choosing among the multiple parallel streams.

 

Cytel has always been a big participant at PHUSE events. Consider these snippets:

  • Several first-time Cytel presenters have won best presentation prizes
  • We have been exhibitors and sponsors at many of PHUSE events
  • A few folks, like Angelo Tinazzi from our Geneva office, are celebrated contributors to a number of PHUSE initiatives. Angelo authored the much-acclaimed eBook The Good Data Submission Doctor on Data Submission and Data Integration to the FDA.
  • A Cytelian, having served as a PHUSE Board Member, and being instrumental in bringing PHUSE to Asia, has been invited to chair the Inaugural APAC Connect. Guess who that is!😊
  • Two more Cytelians, Pratibha Jalui and Sudipta Basu, are serving as Stream Co-Chairs.
  • Angelo will be the EU Connect Chair later this year (he served as the Co-Chair last year) in Glasgow, Scotland.
  • This is the first time ever that Cytelians have been chosen for this privilege.
  • At the PHUSE APAC Connect, we have lots of Cytel presenters: Corey Dunham, Pratibha Jalui, Diganta Bose, Aboli Katdare, Charles Warne, Pradip Maske, Chandan Patel Malyala, and Anoop Rawat. We will also have an exhibit booth (#4) with Mansha Sachdev representing our marketing team.

 

Personally, PHUSE has been a booster rocket for my professional career. It brought numerous opportunities of engaging with three significant audiences:

  • Industry peers, exchanging ideas and co-driving initiatives
  • Prospects among big pharma and biotech, several later became clients
  • A talent pool of bright young professionals, some of whom joined Cytel to enhance our ever-growing brainpower

 

The APAC Connect 2026 has a rich 2.5-day agenda that spans across keynote speeches, panel discussions, presentations, hands-on workshops, software demonstrations, a poster session, and a couple of networking events.

 

The bottomline

We at Cytel have an exemplary track record of bringing rigorous data science to the service of human health outcomes. That’s our raison d’être!

Together, let’s take that forward in 2026 and beyond!

 

Meet with us!

Will you be attending PHUSE APAC Connect in Hyderabad, India, this February? Stop by Booth 4 to get to know our experts and learn how Cytel is shaping the future of data‑driven drug development, or click below to book a meeting to discuss career opportunities at Cytel:

External Control Arms in Drug Development: Methodological and Regulatory Considerations

Drug development is growing more complex, with compressed timelines and increasingly high expectations from regulators, payers, and health systems. In this setting, external control arms (ECAs) leveraging real‑world data (RWD) are emerging as a pragmatic approach to support clinical development and downstream commercial decision‑making.

Randomized controlled trials (RCTs) remain the gold standard for evidence generation. However, in many modern development programs, traditional randomized designs are not feasible or may raise ethical concerns. Sponsors increasingly encounter situations in which:

  • Patient recruitment is slow, limited, or not achievable
  • Randomization is ethically challenging
  • Development costs escalate rapidly
  • Competitive dynamics demand accelerated evidence generation
  • Patient populations are small or rapidly progressing
  • There is a high unmet medical need

 

These challenges are particularly acute in oncology, rare diseases, post‑approval expansion studies, and advanced or cell‑based therapies.

 

What is an external control arm?

An external control arm replaces or supplements a traditional control group by leveraging data from patients treated outside the clinical trial. These patients are drawn from routine clinical practice and reflect outcomes under standard‑of‑care treatment in real‑world settings.

External controls are typically constructed using real‑world data sources such as:

  • Electronic health records (EHRs)
  • Administrative and insurance claims
  • Disease and treatment registries

Unlike trial data, real‑world data reflect patterns of diagnosis, treatment, and follow‑up in everyday clinical care. The foundation of a well‑designed external control study is the use of fit‑for‑purpose data that are sufficiently complete, clinically relevant, and reliable to support robust and defensible analyses.

 

Strategic value of external control arms

When thoughtfully designed and appropriately governed, ECAs can provide meaningful strategic benefits, including:

  • Shortened development timelines
  • Improved feasibility of clinical studies
  • Evidence generation in small or rare populations
  • Stronger value narratives for payers and health technology assessment bodies
  • Support for lifecycle management and label expansion strategies

 

Methodological considerations and risks to manage

The credibility and acceptability of an external control arm depend heavily on methodological rigor.

Key considerations include the following:

1. Study design

External control studies should be designed to closely mirror the clinical trial, including:

  • Alignment of inclusion and exclusion criteria
  • Clear definition of index date and baseline
  • Comparable follow‑up periods and outcome assessment windows
  • Consistent treatment context and line of therapy

Pre-specification of the estimand and statistical analysis plan is critical to avoid post‑hoc decision‑making.

 

2. Patient selection and alignment

Ensuring comparability between trial participants and real‑world patients is one of the most critical aspects of ECA design. Sponsors should:

  • Use transparent, reproducible cohort selection algorithms
  • Apply consistent definitions for key demographic and clinical variables
  • Assess overlap and positivity between trial and external populations
  • Explicitly evaluate differences in baseline characteristics

Sensitivity analyses should be conducted to quantify the impact of residual differences where appropriate.

 

3. Handling confounding and bias

Because external control arms lack randomization, confounding must be actively addressed. Common analytical approaches include:

  • Propensity score methods (matching, weighting, stratification)
  • Multivariable outcome regression
  • Doubly robust methods that combine weighting and modeling

Method selection should be driven by study objectives, data characteristics, sample size, and variable completeness and not for analytical convenience.

 

4. Data quality and missingness

Real‑world data are inherently heterogeneous and incomplete. Methodological plans should address:

  • Data provenance, completeness, and validation
  • Handling of missing or partially observed variables
  • Measurement variability across providers, systems, or data sources
  • Differences in assessment timing and frequency

Imputation strategies and key assumptions should be explicitly documented and tested through sensitivity analyses.

 

5. Outcome definition and assessment

Endpoints derived from RWD must be clinically meaningful and aligned as closely as possible with trial definitions. Considerations include:

  • Use of validated real‑world endpoint definitions
  • Clear attribution and timing of outcomes
  • Consistency with regulatory‑recognized measures of clinical benefit
  • Avoidance of surrogate endpoints unless scientifically justified

Outcome misclassification remains a key risk and should be explicitly evaluated.

 

6. Sensitivity and robustness analyses

Regulators expect evidence that findings are robust under alternative assumptions. Analyses may include:

  • Variation in matching or weighting specifications
  • Alternative cohort definitions or look‑back periods
  • Use of negative control outcomes or exposures
  • Quantitative bias analyses where feasible

The objective is to demonstrate that conclusions are not driven by a single design or modeling decision.

 

7. Transparency and documentation

Methodological transparency is essential for regulatory and payer review. Best practices include:

  • Prespecifying analysis plans and decision rules
  • Fully documenting data sources, algorithms, and assumptions
  • Providing traceability from raw data to final outcomes
  • Enabling reproducibility of key analyses

 

Regulatory outlook and expectations

Regulatory agencies and health technology assessment bodies, including the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Canadian Agency for Drugs and Technologies in Health (CADTH) have recognized the potential role of external control arms under conditions of methodological rigor and transparency.

Regulatory agencies have not lowered evidentiary standards. Rather, they have:

  • Provided greater clarity on scenarios in which external control arms may be acceptable
  • More explicitly articulated methodological expectations
  • Encouraged early and proactive dialogue with sponsors

 

Successful regulatory submissions that incorporate ECAs typically:

  • Provide a clear scientific and ethical rationale for why randomization is not feasible or appropriate
  • Use high‑quality, fit‑for‑purpose real‑world data sources
  • Transparently define patient selection criteria and demonstrate alignment with the trial population
  • Show that findings are robust, reproducible, and minimally biased

Early engagement with regulators remains critical to aligning expectations and maximizing the likelihood of success.

 

Join Anupama Vasudevan and James Matcham on February 3 at 10 a.m. ET for an open office hours on “Evidence Generation with External Control Arms”:

From Regulators to Reimbursement: What the EMA-FDA AI Principles Mean for HEOR

In January 2026, the European Medicines Agency (EMA), together with the U.S. Food and Drug Administration (FDA), have taken an important step by publishing the “Guiding Principles of Good AI Practice in Drug Development.” This document is more than a technical checklist — it is a clear signal that regulators are getting serious about how artificial intelligence (AI) should be developed, validated, governed, and, ultimately, trusted across the medicines lifecycle.

While the principles are formally framed around drug development, their implications go well beyond non-clinical and clinical domains. For Health Economics and Outcomes Research (HEOR), this guidance offers something the field has long needed: a credible regulatory blueprint for responsible AI use that could help agencies move from cautious experimentation to structured adoption.

 

Why this matters now

AI is already being used across HEOR — whether for real-world evidence generation, economic modeling, patient segmentation, or long-term outcome prediction. Yet, despite methodological innovation, acceptance by HTA bodies and payers remains uneven. One of the key barriers is not capability, but confidence: confidence in transparency, robustness, reproducibility, and governance.

By articulating shared principles for AI use, the EMA and its partners are laying the groundwork for that confidence. Importantly, they are doing so in a way that aligns closely with the questions HTA agencies ask every day: What is this model for? What risks does it introduce? Can we trust the outputs? And how do we manage it over time?

 

A bridge to HEOR: Learning from regulatory leadership

We have already seen how regulatory clarity can accelerate adoption. The UK, for example, has actively explored how AI can be used to support evidence generation and decision-making in health systems. EMA-FDA’s principles create an opportunity to extend this momentum across Europe and beyond — including into HEOR and HTA decision frameworks.

Although all ten principles are relevant, four stand out as particularly transformative for HEOR.

 

Four principles with outsized impact on HEOR

1. Human-centric by design

This principle explicitly anchors AI development in ethical and human-centric values. For HEOR, this is critical. Economic models and real-world analyses directly influence access, reimbursement, and, ultimately, patient outcomes.

A human-centric approach reinforces that AI in HEOR should support, not replace, expert judgement. It legitimizes hybrid workflows where analysts, clinicians, patients, and decision-makers remain central, while AI enhances scale, speed, and insight. This framing directly addresses common HTA concerns about “black box” decision-making.

 

2. Risk-based approach

Not all AI use cases carry the same consequences, and this principle explicitly recognizes this. For HEOR, this principle is particularly powerful.

Using AI to automate literature screening does not pose the same risk as using it to inform long-term survival extrapolations or pricing decisions. A risk-based approach allows proportionate validation, governance, and oversight — making AI adoption more realistic and scalable for both developers and agencies.

This is precisely the kind of nuance HTA bodies need to move beyond binary “acceptable/not acceptable” positions on AI.

 

3. Risk-based performance assessment

Closely linked, the EMA and FDA emphasize that performance assessment should consider the complete system, including human-AI interaction, and be tailored to the intended context of use.

For HEOR, this reframes validation away from abstract accuracy metrics and toward decision relevance. The key question becomes: Is this AI fit-for-purpose for the policy or reimbursement decision it supports? This aligns naturally with HTA thinking and opens the door to more pragmatic, decision-focused validation frameworks.

 

4. Life cycle management

Perhaps the most underappreciated principle in HEOR today is life cycle management. The EMA highlights the need for ongoing monitoring, re-evaluation, and management of issues such as data drift.

HEOR models are often treated as static artefacts, yet AI-enabled models evolve as data, clinical practice, and populations change. Recognizing AI as a living system — not a one-off submission — could fundamentally change how HTA agencies think about post-submission evidence generation, managed entry agreements, and reassessment over time.

 

From drug development to HTA: An opportunity not to miss

This guidance is explicitly focused on drug development, but its principles are intentionally broad and collaborative. They invite extension, adaptation, and harmonization across jurisdictions and evidence domains.

For HEOR, this is an opportunity. By aligning AI methods with regulatory expectations early — rather than waiting for explicit HTA-specific rules — the field can help shape how agencies evaluate AI-enabled evidence. In doing so, HEOR can move from being a passive recipient of regulation to an active contributor to responsible AI adoption.

 

Looking ahead

AI will not replace HEOR expertise — but it will increasingly shape how evidence is generated, synthesized, and interpreted. These guiding principles offer a shared language to discuss trust, risk, and value. If agencies apply similar thinking to HEOR, we may finally see a path toward consistent, transparent, and confident use of AI in reimbursement and access decisions.

In that sense, this guidance is not just about AI in drug development. It is about preparing the entire evidence ecosystem — including HEOR — for a future where intelligent systems are used responsibly, transparently, and in service of better patient outcomes.

 

Interested in learning more?

Watch our recent webinar, “AI in HEOR: Case Studies on Navigating Regulatory and HTA Guidance,” on demand, featuring experts Dalia Dawoud, Manuel Cossio, Sheena Singh, and Cale Harrison:

Choosing AI for Clinical Workflows: What the Transparency Index Tells Us About Model Quality

The life sciences industry is reaching a turning point. Large language models (LLMs) are no longer experimental tools; they are becoming embedded in the day-to-day work of protocol writing, SAP drafting, biostatistical programming, data analysis, CSR generation, and even regulatory communication pre drafting. Organizations are beginning to ask not whether they should use AI, but which model they should trust with some of the most sensitive and scientifically consequential tasks in drug development.

This question becomes even more urgent when we look at the 2025 Foundation Model Transparency Index (FMTI), which evaluates how openly model developers disclose information about data, compute, evaluation methods, and governance. The findings show a steep decline in transparency overall. And as illustrated in the graph below, only a handful of companies — most notably IBM, Writer, and AI21 Labs — score above 60%. Many of the most widely used frontier models fall far lower, with OpenAI at 35%, Google at 41%, and Anthropic at 46%. For clinical development teams deciding which LLM to integrate into validated workflows, these discrepancies are too large to ignore.

 

 

Why transparency must be the first filter for model selection

Clinical development is a regulated environment where every analytical step must be traceable, auditable, and scientifically defensible. That makes transparency the first criterion — not model size, not benchmark performance, not popularity. Transparency determines whether you can validate a model’s outputs, understand its failure modes, and integrate it safely into processes governed by GxP expectations and regulatory submissions.

The findings offer a stark reminder that transparency is not evenly distributed across the AI ecosystem. A large gap separates enterprise-focused developers — who tend to score high on transparency — from consumer-facing or hybrid companies, whose disclosure practices are far more limited. For pharma, the companies at the top of the transparency rankings are the ones most aligned with enterprise governance needs.

 

Understanding what really matters: Data, compute, and evaluation rigor

The FMTI highlights where transparency is most lacking: training data provenance and training compute. For clinical development, these blind spots matter because training data influence a model’s understanding of medical terminology, regulatory structure, statistical concepts, and scientific nuance. Without clarity on data sources, organizations cannot evaluate whether an LLM was exposed to clinical trial–relevant content, whether copyrighted text was used, or whether biases exist that could affect outputs like safety narratives or eligibility criteria.

Compute transparency may seem less vital, but it correlates strongly with engineering discipline, model stability, and reproducibility. Models backed by clear documentation of training processes tend to produce more reliable, less erratic outputs — qualities that matter when an AI system is writing code, generating protocol text, or summarizing patient data.

The same applies to evaluation rigor. While many companies publish capability claims, very few release details sufficient for independent replication. The FMTI graph helps contextualize this: companies with the highest scores are also those more likely to provide reproducible evaluations and detailed documentation. These are crucial qualities when determining whether a model can handle clinical tasks such as explaining statistical tests, drafting SAP language, or interpreting adverse event patterns.

 

Choosing the right partner, not just the right model

The transparency disparities shown in the graph underscore an essential reality: selecting an LLM for clinical development is as much about choosing the developer as the model. Enterprise-focused developers consistently outperform frontier labs and consumer-oriented companies because they design their systems with compliance, governance, and documentation in mind.

When evaluating AI vendors for clinical development, organizations should look for evidence of stable disclosure practices, detailed model documentation, governance frameworks, and clarity about training processes. Companies with declining transparency — those trending downward in the FMTI rankings — introduce risk, especially as regulators begin requiring more visibility into the AI systems used in biomedical workflows.

 

A transparency framework for selecting LLMs

Using insights from the FMTI, organizations can apply a simple but powerful sequence when choosing an LLM:

  1. Start with transparency: eliminate models whose developers do not disclose how they were trained or evaluated.
  2. Evaluate domain relevance: determine whether the training data and tuning strategies support clinical and biomedical reasoning.
  3. Assess methodological reproducibility: ensure the model’s documented performance can be independently validated.
  4. Consider governance maturity: prioritize developers with clear update logs, risk policies, and enterprise support systems.

The companies at the top of the graph tend to check these boxes. Those at the bottom typically do not.

 

Transparency by design for AI agents

The 2025 FMTI suggests that as AI systems increasingly take the form of agents embedded across clinical development workflows, transparency may need to be considered early in the design process. AI agents that support activities such as protocol drafting, statistical interpretation, regulatory pre-authoring, or workflow orchestration can introduce additional complexity, particularly when the underlying models operate as opaque systems. In these contexts, limited visibility into how models behave may make validation, monitoring, and risk assessment more challenging.

For those of us in the life sciences industry, the use of AI agents in clinical development may be more sustainable when their behavior and decision pathways can be traced and reviewed. Regulatory evaluation typically extends beyond final outputs to include how decisions were formed and what controls were in place. If AI contributes to protocol language, safety summaries, or analytical reasoning, the ability to explain inputs, assumptions, and limitations could become increasingly important. This, in turn, may depend on working with model providers that offer sufficient documentation around training approaches, evaluation practices, and governance structures.

The transparency differences highlighted by the FMTI indicate that choosing an LLM may also involve selecting a partner with whom long-term governance and compliance considerations can be aligned. Models developed by providers with stronger disclosure practices may offer advantages when building AI systems that require auditability, reproducibility, and regulatory readiness. For organizations exploring the use of AI agents in clinical development, transparency may therefore be one of several factors that influence how confidently such systems can be scaled over time.

 

Read the Foundation Model Transparency Index 2025 report.

The What, When, and Why of the Changes to NICE Methods: Is the Devil in the Details?

Following weeks of anticipation, NICE officially announced in December that the recently rumored increase of its standard cost effectiveness threshold will take effect beginning April 2026.

 

What’s changing and when?

The standard cost effectiveness threshold range that NICE committees use to judge whether a medicine is cost effective will increase by 25% from 20–30K GBP per QALY gained to 25–35K GBP per QALY gained.

NICE stated in its webinar on December 3, 2025, that the Department of Health and Social Care (DHSC) will consult on powers to direct NICE to enact this change starting April 2026, in a targeted change to regulation. This consultation opened on December 9, 2025, and will close on January 13, 2026.

NICE stressed that this targeted change will not mean any broader intervention from government ministers in its methods or decisions. It also confirmed that it is proposing to the government that the new threshold applies across all NICE guidance (Digital, HealthTech, Guidelines) and was awaiting further details. NICE also confirmed in the webinar that it was not aware of any proposals to change the thresholds used to evaluate Highly Specialized Technologies (HSTs) for ultra-rare diseases.

However, the first proposal in the DHSC consultation document refers explicitly to all NICE guidance:

“Do you agree or disagree that the power to direct NICE about the standard cost-effectiveness threshold should apply to all NICE guidance that makes recommendations on health spending? This includes technology appraisal and highly specialised technology evaluation recommendations.

As part of the timeline announced by NICE (see figure), which is subject to consultation, NICE confirmed that in early 2026 it will consult on how this change will be implemented.

 

Anticipated timeline to implement the announced changes (Source: NICE webinar on December 3, 2025)

 

In addition to an increase of its cost effectiveness threshold, NICE also announced it will start using a new EQ-5D-5L UK value set that has been developed by asking 1,200 members of the public to judge different health states and is anticipated to be published in a peer-reviewed publication by March 2026. This change, however, will follow the standard approach to making modular updates to its methods including a public consultation on the proposed change before its full implementation.

NICE’s announcement came in parallel with an announcement from the UK government about the successful closure of a trade deal with the US that includes this change, alongside an agreement regarding the tariff that UK pharmaceutical manufacturers will pay when exporting medicines to the US.

 

Why these changes?

NICE’s methods changes are anticipated to reshape the market access environment in the UK and beyond. The US-UK trade deal, of which this threshold change is part, may convince pharma companies to continue their presence in the UK and to maintain the UK’s positioning in the launch sequence after previously threatening to pull out of the UK market under pressure from the newly announced US tariffs and policies such as the MFN external reference pricing policy.

According to the UK government’s press release announcing NICE threshold changes:

“This is supported by confirmation that — thanks to strong UK support for innovation — the UK has secured mitigations under the US’ ‘Most Favoured Nation’ drug pricing initiative so that we will continue to ensure access to the latest treatments. This will encourage pharmaceutical companies from around the world to prioritise the UK for early launches of their new medicines, meaning British patients could be among the first globally to access breakthrough treatments.”

 

The anticipated impact

These NICE methods changes will have far reaching impact on the assessment of cost effectiveness of medicines in the UK, with likely spillover effects on other countries’ practices as well.

The higher WTP threshold expands headroom for treatments near previous ICER cut-offs, improving the feasibility of charging higher prices for innovative therapies. However, the unchanged discount rate limits the full advantage of this increase. This means more flexibility on price, but continued pressure on future value. It remains to be seen whether this increased threshold will also apply to other NICE guidelines apart from its technology appraisal (TA) program. What has been confirmed is that the threshold change will not lead to any reviews of completed appraisals.

NICE’s adoption of the EQ-5D-5L UK value set will also reshape patient-reported outcomes strategy. Utilities derived from EQ-5D directly influence QALY calculations and ICERs. By reflecting more nuanced health states, EQ-5D-5L supports a more accurate calculation of QALYs. Trials that currently collect EQ-5D-3L data may need a new mapping function to align with the new set. Future trials should prioritize EQ-5D-5L and ensure high completion rates for PRO instruments, as missing data will become even more critical.

From a patient perspective, this means their lived experience is better represented in HTA decisions. For pharma companies, it means interventions that improve pain, anxiety, and functional independence can show their full value in cost-effectiveness models.

 

Regional impact

It is not clear how Europe will respond to these changes on both sides of the Atlantic, but what is clear is that actions will need to be taken to minimize the impact of these changes on both the favorability of European markets as launch markets and the prices to be charged by pharma companies in these markets, both of which are likely to impact patient access to innovative medicines.

Further, we could speculate that this change could bring prices in the UK closer to France and Germany. The UK has been able to achieve low prices because of the powerful negotiating position of the UK’s single centralized payer for the majority of UK healthcare (the NHS), its deeply embedded health technology appraisal processes through NICE, which acts as the gatekeeper for the reimbursement of drugs, and through long-standing price-control mechanisms that effectively cap the NHS’s spend on innovative medicines — the most recent iteration of which is the Voluntary Scheme for Branded Medicines Pricing, Access and Growth (VPAG), and a fallback Statutory Scheme. The current VPAG scheme requires UK manufacturers to pay an effective clawback rate of 23.5% to the UK Government on “newer medicines” (22.9% clawback plus a 0.6% investment program funding, excluding new active substances) — far higher than comparators such as France (5.7%), Germany (7%), and Spain (7.5%).

 

Have you considered these and other impacts and is your team ready for these changes?

A Look Ahead for Biopharma: Embracing Complexity in 2026

Looking back, 2025 was a year of adjustment for biotech — instability shook an already fragile biopharma sector, AI gained significant momentum, the ability to merge open-source code with commercial software matured, and the use of real-world data (RWD) continued to increase. Most companies responded responsibly: pilots, internal capability builds, exploratory regulatory dialogue, and, unfortunately, many had significant layoffs.

2026 is poised to be about embracing complexity — it’s likely many of the trends begun in 2025 will continue, and in addition we’ll see more emphasis on women’s health, an increase in discussions on external control arms, and a spotlight on biostats/clinical pharmacology. From a regulatory perspective, both the US Food and Drug Administration and the European Medicines Agency are signaling the same thing: innovation is welcome, but only when it produces decision-grade evidence.

This has real implications for how drug development companies operate.

Women’s health has expanded beyond a niche category. Regulators are increasingly focused on sex-specific evidence and generalizability across all therapeutic areas. By 2026, this is no longer optional — it’s foundational. In December 2025, the FDA published guidance on studying sex differences, with recommendations to increase female enrollment and strengthen sex-specific analyses and reporting.

Smarter trial designs are now the default. Adaptive approaches, Bayesian methods, external control arms, and decentralized elements are acceptable — expected, even — but only when the assumptions are explicit and defensible. In addition, regulators are clarifying and further exploring the use of various datasets in regulatory submissions; there’s even been a few external control arms presented to regulators.

Behind all of this is a broader shift: biostatistics and clinical pharmacology are moving from support functions to strategic capabilities. Dose justification, estimands, missing data strategy, and model-informed drug development (MIDD) are now central to regulatory credibility.

For biopharma leaders, the message is clear:

For those companies that embrace complexity as the new normal, 2026 offers a powerful opportunity: faster development, clearer regulatory paths, and greater confidence — from regulators, investors, and, ultimately, patients.

Keep an eye out for these new trends in 2026:

 

Women’s health expands beyond a single therapeutic area

Women’s health is no longer confined to reproductive medicine or niche pipelines. Regulators are increasingly focused on sex-specific evidence and generalizability across all therapeutic areas.

In 2026, sponsors should expect:

  • Greater scrutiny of female enrolment and retention
  • Fewer waivers for sex-specific analyses
  • Increased innovation in areas such as menopause, endometriosis, fertility, and autoimmune disease

 

Takeaway: Women’s health isn’t just a therapeutic area; it’s a generalizability requirement. If your statistical analysis plan can’t speak clearly about sex effects (or justify why not), expect pointed questions.

 

External control arms move from optional to strategic

External and synthetic control arms have crossed an important threshold. In 2026, they are no longer seen as novel add-ons but as intentional design choices, particularly in oncology, rare disease, and high unmet-need indications.

Regulatory acceptance is evolving and both the EMA and FDA are leaning in — carefully:

  • EMA is actively developing a reflection paper on external controls (including RWD-derived arms) to shape consistent scientific expectations.1
  • EMA is also doubling down on DARWIN EU, its federated RWE network, with plans to extend work beyond 2027 (tender activity flagged for the first half of 2026).2
  • FDA continues to expand its RWE framing across programs (and sponsors are expected to demonstrate data relevance, reliability, and bias management — not just “we found a database”).3

 

Takeaway: External controls are not a shortcut; they’re a design choice that requires 1) pre-specified causal estimands, 2) transparent matching/adjustment strategy, and 3) sensitivity analyses that are realistic.

 

Biostatistics becomes a strategic capability

Clinical trial design is undergoing a quiet but fundamental upgrade. In 2026, efficiency is no longer achieved by cutting corners, but by thinking better upfront. Biostatistics is no longer a downstream function; it is becoming a strategic driver of development success.

Adaptive and Bayesian designs are becoming mainstream, particularly in early and mid-stage development. Sponsors are expected to define estimands clearly and adequately to address trial objectives, to integrate biomarkers earlier, and to design trials that answer regulatory questions — not just scientific ones. Smaller trials are acceptable; ambiguous trials are not.

In 2026:

  • Estimands, including novel endpoints and strategies for handling intercurrent events, and missing data strategies are key for addressing primary and secondary trial objectives and are strategic topics for assessing drug product’s risk-benefit and totality of evidence.
  • Bayesian methods are increasingly used not just in design, but in regulatory dialogue.
  • Statistics, clinical pharmacology, and translational science should continue moving closer to towards seamless integration.

 

Takeaway: Bringing biostatisticians to the decision-making table early and leveraging quantitative decision-making frameworks will be important for managing overall pipeline decisions.

 

Clinical pharmacology takes center stage

Clinical pharmacology is having a moment — and for good reason. Regulators are increasingly unwilling to forgive poorly justified dose selection, study design optimization, population enrichment, extrapolation, and/or benefit risk assessment/labelling.

MIDD is becoming the norm:

  • Since 2024, FDA is pushing Model-Informed Drug Development via ICH M15 draft guidance and its MIDD meeting program.4
  • EMA is sharpening expectations for mechanistic models (PBPK/PBBM/QSP) used in MIDD, including how they should be assessed and reported.5 A guidance is expected to be completed in 2026.
  • In December 2025, the FDA released a guidance that lists products that no longer need (or can reduce) 6-month non-human primate toxicity testing and, in April 2025, outlined a roadmap for reducing animal testing in preclinical safety studies.6,7

 

Takeaway: In 2026, there will be increased scrutiny in making sure sponsors show why the chosen dose is the best one and can justify the assumptions behind MIDD submitted, or why the approach wasn’t used.

 

Interested in learning more?