When Evidence Gap Becomes a Commercial Liability

For decades and despite calls for better diversity, the geography and population selection for pivotal trials in drugs has remained the same. This was hardly seen as a major source of uncertainty before. But this is changing with the current global shift toward value-based care, which requires local evidence aligned with new care models. Today, uncertainty does not disappear with regulatory approval but moves into formulary and reimbursement negotiations. In most markets, payers now want answers regarding whether the interventions were actually studied with relevant patient data. Especially in the MENA region, this is becoming a common and legitimate question among stakeholders.

The MENA region, including the GCC (Gulf Cooperation Council comprised of Saudi Arabia, the United Arab Emirates (UAE), Qatar, Kuwait, Oman, and Bahrain) Egypt, the Levant, and North Africa, is home to about half a billion people with unique patterns of consanguinity that increases risk of medically inherited conditions, urbanization, risk profile, and care delivery. MENA currently has the world’s highest diabetes prevalence and is expected to have 163 million adults with diabetes by 2050.

What a halted study taught me about assumptions

When I took over an industry-sponsored cardiovascular study in Saudi Arabia at its final stage, I noticed a problem. The study was designed based on risks observed in the U.S. population, predicting similar high rates of cardiovascular events among type 2 diabetes patients in Saudi Arabia, but the observed rates were much lower than predicted. This led to the study being halted at 25% of target recruitment, simply because local patient characteristics and demographics were different from those presented in the U.S.-based study.

The Saudi CAPTURE analysis shows that 18 percent of Saudi adults with type 2 diabetes also had cardiovascular disease, versus 34.8 percent reported in the global CAPTURE study, with a median age of 58 years compared to 64 years respectively. Together with other studies, this demonstrates that the Saudi cardiovascular profile of T2D patients is not the same as what is observed in global trials. And payers based in Saudi Arabia and the wider MENA region are increasingly considering these variations in their decision.

A genomic layer the trial data cannot see

Arab populations have a very different genetic signature when compared with Europeans, who are overrepresented in most global genomic databases. This signature is characterized by founder variants and other common variants that result from demographic histories and high marriage rates between relatives.

Arabs make up about 5 percent of the world population, with only one in 600 represented in major genetic databases. The analysis of 18,360 Arab exomes and genomes showed 2,908 medically relevant founder variants. Of them, 34 percent did not have any record in the global gnomAD database. This creates real uncertainty in the development of several programs, including rare diseases, genetically targeted treatments, and drugs where metabolism affects dose and patient ‘s response.

 The payer question is already here

Recently, in several market access discussions I had in Saudi Arabia, I have seen how the absence of local evidence becomes a major obstacle to new interventions. This obstacle was either underestimated or overlooked at the early stages of planning. Even when local populations are well represented in pivotal trials as is the case in the UK and France, payers still raise concerns when the trial evidence does not reflect local practice. The MENA concerns are similar in nature but more fundamental, because the populations are substantially underrepresented in pivotal trials. This gap between a successful regulator argument and a successful payer argument is exactly where the MENA evidence discussion exists.

A recent Saudi Delphi consensus paper on the evaluation of drugs for rare diseases indicated that the lack of local trial representation and fragmented evidence acted as significant barriers to reimbursement. Evidence gaps in MENA are well documented across multiple therapeutic areas. The 2025 paper in JAMA Oncology by Taha, Meirson, and Waldhorn outlined that despite the well-documented differences in cancer patterns and treatment outcomes in the region, there is extremely low participation of MENA populations in clinical cancer trials.

The regulatory signal from Riyadh

The recent regulatory changes across the MENA region are reflecting what payers are already signaling, and they are more visible in Saudi Arabia. In July 2025, the SFDA made economic evaluation submissions mandatory, followed by a framework for the use of RWD and RWE in April 2026, which names transportability and underrepresented populations as core use cases.

In the same month, the SFDA (Saudi Food and Drug Authority) took a step forward toward evidence localization and introduced the GCC’s first formally codified pre-approval regulatory incentive for pharmaceutical development, the Research and Investigational Drugs Designation (RAID). It offers sponsors rolling MAA (Marketing Authorization Application) submission and priority review, which under the SFDA pathway can cut the review timeline by up to 40%, for trials conducted in the Kingdom on a product not yet authorized globally. Similar trends can be seen in other parts of the region, with Egypt announcing its national pharmacoeconomic recommendations and the Department of Health Abu Dhabi issuing its HTA guidelines.

These changes are demonstrating the regulatory direction and expectations, sending a signal that the outcome of market access discussions is no longer predictable. With regard to the evidence gap, two factors can impact a drugmaker’s market access plan: timing and the competitive landscape. In a less competitive environment, the impact can be limited to higher costs and delayed access. But in competitive markets, the cost can be much higher. This is because local evidence can become a differentiator for first market entry. An early transportability assessment in Phase 2 planning would minimize this risk and make your decision a strategic rather than a reactive one.

The right timing and entry point

MENA has limited capacity and resources to conduct clinical research, in addition to other operational and regulatory challenges. But the way to address these challenges is not to wait for the ecosystem to mature, but to be part of its ongoing maturation. This can be proactively done through partnering with trial-ready sites and supporting their capacity through training, monitoring, and infrastructure investment.

For sure, not every intervention requires a MENA transportability assessment. But certain programs carry increasing commercial risks as regional evidence demands increase, and the rationale for this is supported by clinical realities. Phase 2 planning is usually the right time to conduct the transportability assessment, before population and geography choices are locked into the pivotal design. And some programs should be prioritized for this assessment in MENA. These include drugs with pharmacogenetic sensitivity, and those designed for rare and inherited diseases, where common variants in the region can affect drug metabolism and dosing, condition presentation, and treatment response. Cardio-metabolic and certain oncology programs should also be subject to this assessment as they are frequently associated with substantial variations in the baseline risk profile, patient stage at diagnosis, biomarker data availability, and care pathway compared to Western trial populations and settings.

My message here is that if the MENA region is important commercially to drugmakers, they need to incorporate a transportability assessment into their Phase 2 planning. In response to increasing regional regulatory changes, this will inform early decisions and make population selection defensible. What’s more it will give companies the evidence they will  need for formulary and reimbursement negotiations down the road.

Photo: MirageC, Getty Images

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