One trial is no longer enough. Regulators on both sides of the Atlantic are building a new model of clinical evidence

1. mar 26, 2026

The FDA and the European Commission are changing the rules of the game simultaneously. The shift is from a single pivotal trial to a continuous, multi-year process of evidence generation. For sponsors and CROs, this is not a regulatory update. It is a business model shift.

Within a single month, between December 2025 and January 2026, the FDA issued three major guidance documents, the European Commission announced revisions to the MDR and IVDR, and the EMA formally launched the new HTA pathway. Each of these developments matters in its own right. Taken together, they send a clear message: the model in which the clinical trial served as the central and closed stage of evidence generation is becoming obsolete.

It is being replaced by what is increasingly described as lifecycle evidence. In other words, clinical evidence is now built and tested continuously, from the first patient in a trial through to real-world clinical practice. This is not a theoretical direction of travel. It is a change that is already taking effect.

The US: three guidance documents, one direction

At the start of 2026, the FDA published the draft guidance Use of Bayesian Methodology in Clinical Trials of Drugs and Biological Products. In practical terms, this marks a move away from the rigid model of a single large trial as the primary source of evidence. Instead, it supports an approach in which data are integrated, reinterpreted and used dynamically. This is not just a technical adjustment. It is a signal that the FDA is ready to embrace greater flexibility in trial design, something the industry has been discussing for years.

At the same time, in December 2025, the FDA finalised guidance on the use of real-world evidence for medical devices. The document formally confirms that data from routine clinical practice may be used to support regulatory decisions. Only a few years ago, that would still have been viewed as an experimental approach. At the same time, the FDA makes one point very clear: this is not about “easier” data. It is about data of the right quality, designed and managed in a way that allows for credible interpretation.

The third part of the picture is the December guidance on improving the representativeness of clinical trials. In practice, this means moving away from study populations that are artificially “clean” for statistical purposes, and towards populations that better reflect real conditions of use. This has a direct impact on the value of the data, not only at the point of registration but also later, in clinical and reimbursement decision-making.

Europe: MDR revision, new PMS rules, HTA regulation, and the COMBINE programme

On the European side, the change is more systemic, but it points in the same direction. The proposal to revise the MDR and IVDR, published on 16 December 2025, is formally a response to implementation challenges. Its significance, however, is broader. Simplifying certain pre-market requirements goes hand in hand with reinforcing the lifecycle approach, meaning greater emphasis on data collected after a device is placed on the market.

The MDCG 2025-10 guidance on post-market surveillance, published a few days later, makes that shift tangible. PMS is no longer a purely formal regulatory obligation. It is becoming an integral part of the evidence framework. The quality of data collected after market entry is beginning to directly affect a product’s ongoing regulatory and commercial position.

A further layer comes from the implementation of the HTA Regulation, which has been applied across the European Union since January 2025. The EMA has made it clear that it is ready to support this process. In practice, clinical data are no longer assessed only in terms of safety and efficacy. They are also assessed for their value to the healthcare system. The centre of gravity is shifting from “does it work?” to “does it deliver clinical and system value?”

Against this backdrop, the development of the COMBINE programme is particularly interesting. Its purpose is to integrate regulatory pathways for medicines, devices, and diagnostics. From an operational perspective, this is a highly important signal. Regulators are beginning to adapt to a reality in which medical technologies increasingly no longer fit neatly into a single category.

The requirements are not decreasing. Their distribution over time is changing

When these developments are viewed together, one point is clear: this is not a softening of regulatory expectations. Quite the opposite. The demands placed on clinical evidence are increasing. What is changing is how those demands are distributed over time, and how that evidence is built.

For CROs, this means a fundamental shift in how studies are designed. It is becoming increasingly insufficient to design a trial solely to meet the requirements of a specific regulatory pathway. Increasingly, what is required is the design of an entire evidence-generation programme: from the pivotal trial through the real-world data strategy to the post-market surveillance plan and the preparation of data for HTA.

The risk no longer resides in a single trial. It sits in the lack of consistency across the full programme

In practical terms, this means earlier and deeper involvement from regulatory and operational functions. Decisions on study population, endpoints, or data structure are no longer just matters of trial design. They are now elements of a broader strategy that will have consequences at every subsequent stage, from registration to market access and then to the product’s use in clinical practice.

In my experience, the greatest risk today is not non-compliance with a single regulatory requirement. It is the lack of consistency across the programme as a whole. Programmes planned in fragments, with the trial, PMS, and HTA approaches designed separately, are increasingly running into problems. Those problems do not stem from the quality of an individual component. They stem from the lack of integration between them.

A new role for the CRO: strategy partner, not protocol executor

This is why the CRO role must evolve as well. Efficient trial delivery is no longer enough. What becomes critical is the ability to co-create the evidence strategy with the sponsor, bringing together regulatory, operational, data, and market access requirements into one coherent model.

In that sense, the shift we are seeing is less a regulatory change than a paradigm shift. We are moving from a model in which clinical evidence was the “output” of a trial to one in which it is a continuous, multi-source process, increasingly integrated with real-world clinical practice.