Most Ex-U.S. Countries Can't Access The Medicines They Help Study
By Jennifer E. Miller, Ph.D.
When a country hosts a clinical trial for a new medicine, most of us assume patients there will eventually benefit from the therapy they helped test. That’s the spirit of the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) guidelines: Populations who bear the burdens of research should share in its benefits.
Our new study suggests this assumption is often wrong.
Looking at all 172 novel medicines approved by the FDA from 2015–2018, we asked a basic operational question with big ethical implications: Are these medicines physically accessible, i.e., granted marketing authorization, in the countries where they were tested, and has access improved over time?
The answer: For most trial-hosting countries, especially low- and middle-income countries (LMICs), the medicines never arrive or arrive years late.
What We Did
We identified every Phase 2 and 3 trial supporting FDA approval of novel drugs and biologics from 2015–2018, then matched those trials to ClinicalTrials.gov to determine where they were conducted. That gave us 885 trials in 89 countries for 172 medicines approved by the FDA.
For each country hosting at least one trial, we asked: Did this medicine obtain marketing authorization here within five years of FDA approval? We treated marketing authorization as a narrow but essential definition of “access,” as you generally can’t prescribe, procure, or distribute a medicine at scale until it is authorized.
What We Found
A few key statistics capture the core story: Of the 144 medicines tested outside the U.S., only 24% were physically accessible in all the countries where they were tested within five years of FDA approval. Among the 77 countries that publicly report marketing authorizations, just 14% had physical access to all the medicines they tested at five years.
Access was highly unequal. While in Western Europe, 82% of tested medicines were physically accessible within five years, in Africa, only 28% of tested medicines were accessible in those countries where they were tested. By income level, high-income countries had significantly better access than lower-income countries.
Timelines also diverged sharply. When FDA approved these medicines, Western Europe gained access in a median of four months. African countries waited a median of 40 months, roughly 10 times longer — if they got access at all.
We also saw troubling trends: High-income countries’ access to medicines has improved over time. For drugs approved from 2015–2016, 22% were accessible in all high-income trial-hosting countries which rose to 38% for 2017–2018 approvals. In contrast, we saw no significant improvements in access for upper-middle or lower-middle income countries over the same period. In some regions, including Asia and the Middle East, the proportion of medicines accessible in all trial-hosting countries has declined.
Low-income countries were largely left out twice: Only three medicines in our entire sample were tested in a low-income country and, even then, physical access was inconsistent. For example, an HIV combination regimen tested in Uganda and Zimbabwe became accessible in Uganda but not in Zimbabwe within five years.
The “Test It, But Don’t Sell It” Problem
For years, research ethics has focused on the opposite problem: Medicines are sold extensively but not tested in key populations who use them (the “don’t test, but do sell” problem). For example, cancer therapies marketed to U.S. patients often lack adequate representation of women, older adults, and racial and ethnic minorities, among other groups, in pre-approval trials.
Our work highlights the mirror image: Countries that host trials often never see the products brought to their market. We are calling this the “test it, but don’t sell it” phenomenon.
In practical terms, this means:
- Health systems allocate staff and infrastructure, and connect patients to global development programs.
- Those populations assume the risks of experimental interventions and research participation.
- Years later, they still can’t prescribe or access the resulting medicines in routine care — or can only do so after long delays.
Why This Matters
Country site selection decisions carry ethical obligations
When we choose to open sites in a country, we acknowledge that the country carries a substantial burden of a targeted disease. And, we implicitly signal that this population matters for the evidence base. But, don’t they matter more than just what they can do for a sponsor, to help generate clinical trial data? Our research suggests that, in many cases, those same countries are not prioritized for regulatory submission and product access. Using a population for evidence generation without access provision can be considered exploitation. To be sure, there are other access pathways beyond commercial, but they aren’t consistently used or transparent.
There Are “Bright Spots” To Learn From
Even within regions with poor overall access, some countries, such as Ethiopia and Uganda in our sample, achieved full physical access to the medicines they tested. Understanding what worked there (policy, regulatory capacity, procurement, partnership models) could help other countries achieve similar success. We are now leading an initiative, thanks to a Yale and the World grant, to create the Yale Medicines Access Network (YMAN) which will bring together heads of oncology centers and ministers of health, from both bright spot countries and countries struggling to secure physical access to products they test, in regular convening to help address this challenge.
From Voluntary Guidance To Measurable Expectations
The ethical expectations around how to treat patients and populations testing new medicines are not new. The Declaration of Helsinki and CIOMS guidelines have implied for about a decade that populations participating in research should have post-trial access to proven interventions. Our findings show that voluntary guidance alone hasn’t been enough to shift practice in a meaningful way, especially for LMICs.
This suggests the need for:
- Clearer guidance, negotiation power, and enforcement from ethics committees, regulators, and funders, including expectations that sponsors articulate realistic post-trial access plans during protocol development and site selection and set up.
- Regional solutions, such as regulatory harmonization efforts (e.g., the African Medicines Agency) that can lower the barrier to filing marketing applications, shorten lag times in review and access across multiple countries, and increase regional purchasing power.
- Performance metrics that make post-trial access visible and comparable across companies.
On that last point, we are integrating this “test it, but don’t sell it” dimension into the Good Pharma Scorecard, which rates and ranks companies on their bioethics performance. For industry, this offers both a risk (being seen as lagging peers) and an opportunity (demonstrating leadership on fair benefit-sharing).
What You Can Do Now
For sponsors, CROs, and clinical operations teams, a few concrete steps can move practice closer to ethical guidance without waiting for new regulations:
- Coordinate regulatory and clinical strategy.
Ensure that global regulatory teams and clinical operations are aligned from the start: Where you test a medicine should inform where you plan to file for approval and on what timeline. - Engage early with regional regulators and payers.
In regions with emerging harmonization efforts, sponsors can collaborate with regulators to understand requirements, share data, and explore reliance models that can accelerate access. - Track and report your own “test it, but don’t sell it” footprint.
Internally, calculate: Of all the countries where we have run pivotal or key Phase 2/3 trials in the last five years, how many have a corresponding marketing authorization, and how long did it take? Treat this as a KPI alongside traditional metrics like first patient enrolled and time-to-approval. - Partner with bright-spot countries.
Where countries have successfully translated trial participation into timely access, consider them not just as sites but as strategic partners in designing scalable regional models.
The globalization of clinical research was sold, in part, on a promise that patients and health systems in trial-hosting countries would share in the benefits of innovation. Our study shows that this promise remains unfulfilled for many countries, especially in Africa, Latin America, and parts of Asia and the Middle East.
This is a moment to move beyond compliance with minimum standards and toward proactive, measurable, and equitable access strategies. The goal is simple: If a country helps you test a medicine, patients there shouldn’t have to wait years, or forever, to see it on the shelf.
Editor’s note: This article is based on the JAMA Internal Medicine article, “Physical Accessibility of Medicines in Countries Hosting Trials for FDA Approvals.”
About The Author:
Jennifer E. Miller, Ph.D., is co-director of the program for biomedical ethics and an associate professor of internal medicine and of biomedical informatics and data science at Yale School of Medicine. She is also the director of the Good Pharma Scorecard (an index that ranks and rates pharmaceutical companies on their bioethical performance) and the nonprofit Bioethics International.
Her current research focuses on ethics, access, and governance in medicines development and commercialization, AI-enabled medical care, and healthcare data sharing. She also specializes in developing and using metrics to enhance accountability and social responsibility in biomedical innovation.