Top Experts Say The FDA’s New Guidelines For Clinical Trials Have Huge Implications For Patients, The Crucial Research That Saves Lives

This shift signals a move toward more patient-centered outcomes, especially for drugs seeking accelerated approval, which often rely on surrogate endpoints like progression-free or event-free survival, which is the time during which cancer is controlled before it begins growing again.

The FDA’s new guidance is being met with caution by several leading cancer experts, some of whom are raising red flags about the unintended consequences.

Dr. Brendon Stiles, Chief of the Division of Thoracic Surgery and Surgical Oncology at Montefiore-Einstein Comprehensive Cancer Center, warns that the policy—though well-meaning—could hinder innovation and delay access to life-saving treatments.

“A rigid mandate favoring overall survival as a primary endpoint—regardless of context—threatens to slow drug development, raise costs sharply, discourage entry into rare or rapidly evolving oncology indications, and undermine clinically meaningful surrogate-based insights,” Dr. Stiles tells SurvivorNet.

“Although overall survival remains the ‘gold standard’ for certifying survival benefit, mandating it universally overlooks nuance, increases cost and duration, dampens innovation, and delays therapies for patients who need them now,” Dr. Stiles added.

On the other end of the spectrum sits Dr. Raja Flores, Chairman of Thoracic Surgery at Mount Sinai Health System, who has long advocated for this change.

“I think the updated guidelines are a good thing. But again, it depends on your stage,” Dr. Flores told SurvivorNet.

“I’ve been voicing my concerns for a while now, for using these surrogate markers like event survival and not overall survival,” Dr. Flores continued.

While he supports the FDA’s updated guidance, Flores emphasizes that treatment decisions must still be tailored to each patient’s diagnosis and encourages patients and their loved ones to talk to their care team before deciding on treatment.

Understanding the Endpoints

• Event-Free Survival (EFS): Time after treatment during which a patient remains free of complications like recurrence or new symptoms.
• Progression-Free Survival (PFS): Time during which cancer is controlled before it begins growing again.
• Overall Survival (OS): This refers to how long people live after getting the treatment.
• Disease-free survival: This refers to the time between observable progress in curing cancer and signs that it started growing again.

While these surrogate endpoints can still be used, the FDA now requires them to be backed by robust overall survival data.

To avoid skewing overall survival results, the agency also recommends limiting crossover trial designs, unless no alternative treatments exist.

What This Means for Patients

Even with the FDA tightening its rules around overall survival data, there’s still room for hope. Drugs that show strong results through other measures—like intermediate endpoints—can still get accelerated approval. That’s important for patients dealing with advanced cancer who might need access to treatment sooner rather than later. But it’s crucial to talk things through with your doctor, especially when the treatment is based on surrogate markers like progression-free survival or event-free survival.

When you or someone you love is facing a tough diagnosis, the flood of medical terms and treatment options can feel overwhelming. But if you can get a handle on concepts like “overall survival” and “progression-free survival”, it can be game-changing. You’ll be able to ask better questions, understand your treatment options more clearly, and work with your care team to build a personalized treatment plan that truly fits your needs.

FDA’s Push for Overall Survival as Primary Endpoint Sparks Concern Among Some Cancer Experts

“The FDA’s focus on overall survival is a well-intentioned but misguided initiative,” Dr. Stiles tells SurvivorNet.

“While improving overall survival—and quality of life—should be the goal of any new cancer therapeutic, overall survival as a primary, or even required, endpoint in oncology trials falls short on key practical and economic issues,” Dr. Stiles added.

Dr. Stiles points to the significant time and financial burdens associated with OS-focused trials. According to studies cited in JAMA Internal Medicine and SAGE Journals, surrogate endpoints like progression-free survival (PFS) or event-free survival (EFS) can shorten trial duration by 11–19 months and reduce costs dramatically. In contrast, trials using OS as the endpoint can cost more than double—averaging $79.4 million per phase III trial.

“Mandating overall survival endpoints would not only slow drug development but also raise costs considerably,” Dr. Stiles explained. “This would likely reduce innovation and put trials out of reach for smaller developers.”

Dr. Stiles also cautioned that such a mandate could discourage research into rare or rapidly evolving cancers, narrowing the field of investment and leaving patients with fewer therapeutic options.

Beyond logistics, Dr. Stiles highlights the interpretive challenges of OS data. The FDA itself acknowledges that crossover treatments, subsequent therapies, and inconsistent post-progression care can confound OS. Data from the academic journal BMC Cancer show that only 11–48% of trials report assessable post-progression data, and many reflect substandard care.

“Confounding factors undermine overall survival interpretability,” Dr. Stiles said. “In contrast, surrogate endpoints provide clinically meaningful and faster insights.”

Dr. Stiles emphasized that progression-free survival and event-free survival are objective, measurable earlier, and less susceptible to downstream confounding—making them valuable tools for assessing disease control and symptom relief, especially in advanced-stage cancers.

Dr. Stiles acknowledges that surrogate endpoints – an indicator or sign used in place of another to tell if a treatment works – aren’t always predictive of overall survival, citing data from the Journal of Clinical Oncology. But he argues that this variability should prompt better validation and not blanket rejection.

“This simply emphasizes the need for more rigorous validation of surrogates and confirmatory overall survival data when appropriate,” he said. “Not every trial and every drug approval must wait for overall survival readouts.”

WATCH: What to Know Before Enrolling in a Clinical Trial

One Size Doesn’t Fit All: New FDA Oncology Standards May Affect Patients Differently by Stage

Dr. Raja Flores expresses support for the FDA’s emphasis on overall survival in oncology trials, recognizing its value as a meaningful endpoint. However, he cautions against applying this standard universally. He notes that early-stage cancer patients may not benefit from the same aggressive treatment strategies typically pursued in metastatic cases, and urges a more nuanced, patient-specific approach to trial design and therapeutic evaluation.

“In some early-stage cancers, it can prevent certain treatment options,” he explained. “But in late-stage cancers, getting the cancer treated as quickly as possible and being as aggressive as possible with treatment is essential,” Dr. Flores tells SurvivorNet.

Flores warns that relying too heavily on surrogate endpoints in early-stage cancers could inadvertently reduce survival chances.

“Take lung cancer, for example. If a patient gets a drug before surgery and it doesn’t work, you’ve decreased patient survival by a certain amount,” he said.

“So, it’s important to make sure when something is being passed through the FDA—and you may have a good response rate—you’re not hindering the cure. Overall survival is better than event-free survival.”

Dr. Larry Norton on the Broader Value of Anti-Cancer Therapies

While overall survival remains a cornerstone of cancer research and treatment, Dr. Larry Norton—Medical Director of the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center—believes it’s time to expand the conversation. Anti-cancer drugs, he says, offer benefits that go far beyond extending life.

“We should also remember that anticancer drugs can help patients in other ways too,” Dr. Norton tells SurvivorNet.

He emphasizes that treatments which may not significantly impact survival rates can still play a vital role in improving a patient’s day-to-day experience. By reducing tumor size and alleviating symptoms, these therapies can enhance comfort, mobility, and emotional well-being.

“Shrinking cancers so that they cause fewer symptoms can extend the duration of a patient’s quality of life even if overall survival is not improved,” he explains.

Dr. Norton also points to the potential of combination therapies. Even if individual drugs don’t extend survival on their own, they may work synergistically to produce meaningful outcomes.

“Sometimes medicines that do not extend overall survival by themselves can be combined to provide that impact,” he says. “And cancer shrinkage—partial or complete response—is an endpoint in that direction.”

RELATED: An Evidence-Based Approach to Discussing Clinical Trials With Your Patients 

What to Consider When Clinical Trials Are an Option?

Within the U.S., all new drugs must go through clinical trials before the FDA approves them. Although the rewards of clinical trials can be great, they also come with risks. Talking to your doctor about this before enrolling in a trial is important. Some risks to consider include:

• The risk of harm and/or side effects due to experimental treatments
• Researchers may be unaware of some potential side effects of experimental treatments
• The treatment may not work for you, even if it has worked for others

WATCH: Clinical trials can be life-saving.

Before you enroll in a trial, you must be allowed to read the consent documents thoroughly and to ask any questions you may have. The documents will likely contain the following:

• The purpose of the research
• Any risks and benefits expected from the research
• Information about procedures that may cause discomfort (like frequent blood tests)
• Any alternative procedures the patient might consider instead
• How the patient’s information will be kept private
• How long is the study expected to take
• A form confirming you are participating in research voluntarily
• Whether any compensation or additional medical care is available if some sort of injury occurs
• The patient’s rights (like the right to stop research in the middle of the trial)
• Contacts for any patient questions

Patients are allowed to walk away at any time during the trial. Understanding your rights as a voluntary patient is important before you participate in a clinical trial, and understanding that the treatment may not work is also crucial.

Do Clinical Trials Cost Participants Anything?

Clinical trials may also have no extra cost for the participants, as the study’s sponsor may pay for the treatment and any additional care. Some sponsors even pay for travel to and from appointments or treatment centers. Patients should ask what will be paid for before signing up to be part of a trial.

The ‘Placebo’

During the treatment of an experimental drug in a clinical trial, while some participants receive the real thing, others do not. These participants receive a placebo.

The placebo is “an inactive substance or other intervention that looks the same as and is given the same way as an active drug or treatment being tested. The effects of the active drug or other intervention are compared to the effects of the placebo, as defined by the National Cancer Institute.

In some cancer clinical trials that are “randomized,” patients who enroll are randomly assigned to receive either a placebo or the new experimental drug being studied. If the clinical trial is “double-blinded,” that means that neither the patients nor the doctors running the clinical trial know who’s in which group. This is an important part of a clinical trial design because it safeguards against bias and the possibility of skewed results.

It’s important to know that getting zero treatment isn’t usually the reality of the “placebo arm” anyway.

Instead, when patients with life-threatening cancers enroll in randomized clinical trials, the two groups are often broken into the new, experimental drug and a “control” group that receives the “standard-of-care” treatment.

Treatments considered standard of care are those that experts accept as the go-to treatment for specific cancers. Standard-of-care, in other words, is the most used treatment.

In many cases, it might involve a combination of chemotherapy, surgery, or radiation, but not always.

How to Find a Clinical Trial

If you want to participate in a clinical trial, your first step should be to talk with your doctor. They can address many of your initial questions and help you determine if you would make a good participant.

Another crucial part of clinical trials is finding the right one for you. SurvirorNet has a resource to help with this called the Clinical Trial Finder.

The portal provides resourceful information to more than 100,000 active clinical trials. You can research this tool for yourself or someone else based on a few simple questions about your condition and location.

Learn more about SurvivorNet's rigorous medical review process.

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