The day after Christmas in 2019, Annette Harlow received what would be the final infusion of her lung cancer therapy. Just weeks later, in a doctor’s office in Lake Charles, La., she heard the news every cancer patient dreads: the treatment had stopped working. “Is that it?” she asked. “I’m afraid so,” she recalled her doctor saying. “Right now, there’s nothing that we have for you.”
The very next day, she received a message through her patient portal: If her tumor carried a mutation in a gene called KRAS, she might qualify for a clinical trial run by Dr. David Hong in Houston. “You could see my spirit just flying in the room. There was something for me,” she said, her voice lifting at the memory. The test on her tumor came back positive. Soon, she was making the two-and-a-half-hour drive to the University of Texas M.D. Anderson Cancer Center, having enrolled in Dr. Hong’s Phase 1 clinical trial.
The experimental drug she received there, sotorasib, blocks a mutant version of the KRAS gene, which for decades scientists had considered resistant to drug therapy. Ms. Harlow was among the first people in the world to take it. More than six years later, she is an energetic and optimistic woman in her late 80s, and her cancer is under control. “I have had many blessings in life,” she wrote in an email, “and for sure the two most remarkable ones have been Dr. Hong and sotorasib.”
A Phase 1 clinical trial is the initial point at which a potential treatment leaves the laboratory and meets human reality. Every drug that reaches approval for the general public must pass through this gate. We owe the whole of modern medicine to countless trials like it. And for patients with advanced cancer, they offer what is often a last hope.
As the deputy chair of M.D. Anderson’s Phase 1 program, Dr. Hong is among the country’s leading academic oncologists. He has spent his career translating the latest discoveries from the laboratory into the clinic, offering second chances to patients who have run out of all other options. Not all his patients are as lucky as Ms. Harlow — but he has seen enough patients recover from supposedly fatal diagnoses to appreciate what new, innovative drugs can do. In August, the Food and Drug Administration approved daraxonrasib, a therapy that almost doubles survival rates in pancreatic cancer, one of biology’s most ruthless killers. Dr. Hong led the Phase 1 trial that first showed the drug could work in humans. If anyone has reason to be triumphant about American drug development, he does.
But when we spoke, Dr. Hong was not triumphant. He was worried. He told me that the system that gave Ms. Harlow her life-extending treatment is under serious strain. The cost of running a clinical trial in the United States has climbed steeply in the past decades. For Phase 1 trials specifically, the cost for generating the evidence needed just to open one has doubled, on average, since 2017, and for some complex therapies the cost can reach several million dollars per patient.
In response, drug companies are opening fewer trials than they otherwise might have, and they are increasingly taking the ones they do conduct abroad, to countries such as Australia and China. That leaves American patients with fewer chances to enroll in a clinical trial. The timing makes this especially bitter: A.I. and the genomics revolution are turning long-promised ideas into potentially curative therapies.
It is no longer the science, Dr. Hong believes, that is holding back potential cures, but our capacity to try new medicines in clinical trials. His fear, echoed by the many oncologists and medical experts I interviewed, is that the most important science may happen elsewhere or not at all. “For the first time, patients in America will no longer be among the first to benefit from the latest biomedical discoveries,” he told me.
The damage is hard to assess: the trials that were never run, the breakthroughs that never happened. What we do know is that the search for new cures is broken. We can’t always ask for or expect medical miracles, but we can demand a system that gives doctors the best chance to save lives.
Much of the slowdown in drug development has been caused by the accumulated weight of decades of regulatory requirements, piled one atop another over years. The paperwork burden alone can be enormous: Novo Nordisk’s former chief scientific officer once noted that the documentation required to request approval for two insulin products, if printed and stacked, would rise higher than the Empire State Building.
That accumulation follows from a medical framework that treats any potential risk, however negligible, as something that must be mitigated and a reason to delay — while drastically underweighing the cost of delay itself. Regulatory agencies, hospitals and drug companies all cover themselves against litigation or blame. But responsibility for mitigating the second, often much greater risk — that the disease afflicting the patient takes advantage of the delay, with potentially deadly results — belongs to no one. “We often forget that the most toxic thing for the patient is the cancer itself,” Dr. Hong said. In many cases, he can recount, down to the month, how much longer his patients are expected to live, which is why weeks lost to paperwork are not abstract to him.
The shadowy nature of the drug-development system helps explain, at least in part, how we arrived here. Most of what happens between a drug developer and the F.D.A. is invisible: Communications are largely confidential, and the requirements attached to clinical trials are rarely published or compared across cases. But I have spoken with dozens of the researchers who work inside this system, and their accounts point in the same direction.
The frustrations they describe stretch across every level of the system. One is redundancy. Often, the same trial plan will be reviewed by separate ethics boards (also known as Institutional Review Boards, or I.R.B.s) at different hospitals, on top of a review cycle at the F.D.A., even though the National Institutes of Health has for years urged the opposite. These reviews can sometimes drag on for months, often for purely procedural reasons, even though there’s no evidence that such long reviews increase patient safety.
And then there are the F.D.A.’s manufacturing standards, the set of rules for how a new drug must be produced. Academic clinicians repeatedly told me that these have become the largest bottleneck to getting novel cell and gene therapy treatments to patients with advanced cancers. To meet these standards, developers typically must make their material in specialized facilities, certified to commercial-scale standards.
The problem is that doing so makes little sense for early-phase trials that just need a tiny batch of medicine for what might be a handful of patients. And by substantially increasing manufacturing costs, the rules can result in clinicians offering these experimental therapies to only a fraction of potentially eligible patients. (The F.D.A. claims to offer exemptions from full manufacturing requirements for Phase 1 trials, but the exemptions are so vague that medical researchers tend not to take advantage of them.)
Slower and costlier trials are one reason the number of new drugs approved per billion dollars of research and development spending has roughly halved every nine years since the 1950s, with an apparent plateau in the past 10 years. Researchers have a name for this phenomenon: Eroom’s Law. It’s a deliberate inversion of Moore’s Law, the semiconductor industry’s famous principle of exponential progress. Whereas Moore’s Law tracks a world of compounding gains, Eroom’s Law shows the opposite: The more we spend on drug discovery, the less we get.
A few converging forces make this bottleneck more consequential than ever. The first force is scientific progress itself. Science is creating treatments that the regulatory system was not designed to handle. The most striking case is that of personalized medicine: Thanks to technological advances in recent decades, we can now sequence a patient’s tumor to find out its specific vulnerabilities, and increasingly we can tailor therapies to the needs of specific individuals.
Yet a medicine designed for one person cannot, by definition, prove itself in the large trials ordinarily required for approval. In practice, getting such a medicine often involves clearing some of the same regulatory steps as starting a Phase 1 trial, which also means coming up against similar barriers and delays.
Pierce Ogden, a co-founder of the biotechnology company Manifold Bio, encountered these barriers after his 74-year-old father was diagnosed with advanced glioblastoma, an aggressive form of brain cancer, in June 2025. Advanced molecular analysis revealed high levels of a certain protein, known as DLL3, in his father’s tumor. Dr. Ogden believed that a drug known to target this protein and already approved for a different type of cancer could be a good candidate for his father. Amgen, the company that developed the drug, agreed to supply it and helped seek special F.D.A. permission.
Yet the process of starting the treatment dragged on. For one thing, Dr. Ogden was told that the hospital’s ethics committee met only once a month, which added weeks of delay. In April 2026, after months of dealing with administrative barriers, he eventually found another doctor and hospital willing to administer the drug. By then, however, his father’s cancer had progressed considerably, and he died the following month. As Dr. Ogden put it, “Everyone tried their best, but the system is so convoluted and risk-averse that it is very hard for anyone to do anything to speed the process up.”
His struggle is shared by an increasing number of patients and their families. In reporting this piece, I spoke with a dozen cancer patients who had attempted some version of what Dr. Ogden did, with varying degrees of success. Some hired what amounted to an army of regulatory consultants to navigate the system. Sid Sijbrandij, a co-founder of GitLab, took this route after his bone cancer relapsed, pursuing personalized treatments for his tumor. He has now been cancer-free for a year — an extraordinary outcome for a cancer generally considered incurable.
Some patients have left America to pursue treatment abroad. Patrick Salisbury, a former technology executive, took his 13-year-old daughter, who has osteosarcoma, to Germany to receive a personalized cancer vaccine designed specifically for her by a team of American academics.
German law recognizes a framework called Heilversuch, or “healing attempt,” under which a physician may act on his own clinical judgment with the patient’s informed consent and without a regulator’s sign-off. A clinician at a reputable academic center decided on a Tuesday evening to give Mr. Salisbury’s daughter a personalized mRNA vaccine, and the vaccine was administered to her a few days later. Pursued in the United States through a single-patient trial, the same treatment would have taken months, time she did not have.
What all these paths have in common is that they are not available to patients without substantial amounts of money, or a network that can point the way to gaining access to these therapies abroad. A majority of Americans do not have this level of resources or standing within the health care industry. Yet this inequality of access is not inevitable, but in part a result of the system we have chosen. The academic clinicians I interviewed wanted to help identify and pursue the most advanced treatments for their patients — it is, after all, what they understand their duty to be — but felt their hands were tied by the red tape of bureaucracy. The same reforms that would make Phase 1 trials faster and cheaper would also help put personalized therapies within reach.
The second force making the problems of clinical trials especially pressing now is a structural shift in the labs where drug innovation originates. It’s no longer mostly done in large pharmaceutical companies. In the period between 2010 and 2020, big companies were involved as originators in only a quarter of first-in-class cancer drugs — the type of drugs that open entirely new categories of treatment rather than just iterating on existing ones. Instead, those breakthroughs are now heavily concentrated in small companies and academic labs.
But small companies and academic labs are much more vulnerable to the high cost of clinical trials. A large pharmaceutical company can absorb a failed or delayed trial, and has the regulatory know-how to navigate complex F.D.A. requirements, while a biotech often cannot.
The final force is competition from China. Over the past decade, China has built one of the most productive clinical development environments in the world by revamping its regulatory system and allowing faster trials. Its system allows drug developers to move through early-stage studies more quickly, generate data, adjust and iterate — compressing the learning cycles that in the United States can stretch for years. Chinese biotechs are increasingly becoming the place where the world’s most consequential clinical research gets done: In fact, around half of drugs licensed by Big Pharma are now coming from there. Just 10 years ago, that figure was around 5 percent.
But the Chinese system has weaknesses. Recent investigations uncovered two deaths in experimental gene-therapy studies, which went undisclosed for months or longer. While such events are not the norm, they do expose serious failures, particularly because in one case the researchers appeared to have ignored serious safety red flags from the tests conducted in animals. But duplicative reviews, excessive manufacturing requirements and administrative delays are not the right safeguards either. The lesson for the United States is not to eliminate all safeguards indiscriminately, but to draw the line between genuine protections and procedural obstacles.
We know this can be done better, because other regulatory environments have proved it. Dr. Alison Schram, an academic oncologist at Memorial Sloan Kettering Cancer Center, told me that the biotech companies she collaborates with on clinical trials are increasingly choosing to test their drugs in hospitals in other countries, especially Australia. This hurts not only American patients, who miss out on experimental treatments, but the whole American scientific enterprise, by breaking the feedback loop between the lab and the clinic. “America is still leading in terms of basic science,” Dr. Schram said. “But there must be a dialogue between what is discovered in the lab and what is tested in patients.”
But the same flight to Australia is not just a warning; it also points to an opportunity. Australia has run these trials safely for years, and with a great degree of transparency, unlike China, showing that greater speed can be achieved without compromising patient safety. The United States should pay close attention.
Before a new therapy can be tested in people in the United States, its sponsor must file what is known as an Investigational New Drug application. The submission can run to hundreds and even thousands of pages and includes extensive detail on manufacturing processes and quality controls, much of it designed with later commercial production in mind. What Australia does instead is focus on the questions related to evidence that the therapy is safe, which is what matters most in an early human study.
The result of the Australian system is that much-needed drugs are available faster to patients. Australia can cut up to nine months from the timeline before the application to start a trial is submitted, and another three to six after that. For a biotechnology company spending $2 million per month, this gap can be the difference between surviving and folding. For investors in a company, this regulatory environment can spell the difference between launching a venture and not starting the company at all. And most important, for patients like Ms. Harlow, even a month can mean the difference between survival and death.
The good news is that the case for reform has started to reach policymakers in America. In June 2026, the Department of Health and Human Services and the F.D.A. launched Operation TrialBlazer, a pilot program aimed at compressing timelines for first-in-human trials by roughly six to 12 months, modeled after Australia’s Phase 1 trial system. One of the most encouraging aspects of this announcement was that the initiative directly acknowledges many of the issues that I heard about from my interviewees, including duplicative review and excessive manufacturing requirements. But the F.D.A. has a long history of announcing reforms that stall. Real change will require Congress to pass legislation.
The window of opportunity is tight. Next year, Congress is set to reauthorize the legislation that allows the Food and Drug Administration to collect fees from pharmaceutical companies. Because reauthorization is effectively must-pass legislation, it forces Congress to focus on the agency and offers the best opportunity to attach major F.D.A.-related reforms.
Dr. Hong believes that adopting an Australian-style model — one that preserves safety while improving efficiency — would accelerate the discovery of new drugs and bring more of them within reach of more people, with effects that will stretch across decades. But they are also about the patients who need treatments now, like Annette Harlow. This is a woman who walked into her doctor’s office weeks after Christmas being told there was nothing left, and who has since enjoyed six more Christmases thanks to the therapy she received in a Phase 1 trial. What the fight is really for, in Dr. Hong’s words, is “a United States with more Annette Harlows.”
Ruxandra Teslo writes about clinical trials and technological progress in her newsletter Ruxandra’s Substack and on the Clinical Trials Abundance blog.
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