Critical Information Gap: Most Cancer Drug Uncertainties Missing from Journals and Guidelines

New research reveals patients and doctors aren't getting the full picture on treatment limitations

Bottom Line: Recent landmark research published in JAMA reveals a troubling transparency gap in cancer drug approvals. Nearly 80% of cancer drugs approved by the FDA from 2019-2022 had clinical uncertainties that were rarely communicated to doctors through journal publications or clinical guidelines—potentially leaving patients uninformed about important treatment limitations.

The Research Findings

A comprehensive study led by researchers at the London School of Economics examined 52 cancer drugs approved by the FDA between 2019 and 2022. The results paint a concerning picture of information transparency:

Key Statistics:

  • 79% of cancer drugs (38 out of 48) had clinical trial uncertainties highlighted in the FDA's Benefit-Risk Framework
  • Journal publications reported only 22% (21/94) of the uncertainties identified by FDA reviewers
  • Clinical guidelines reported only 23% (22/94) of these uncertainties
  • More than half of publications (53%) and 47% of guidelines reported none of the identified uncertainties

What Are These "Uncertainties"?

The uncertainties identified by FDA reviewers included critical issues such as:

  • Long-term benefits and harms (most common category)
  • Single-arm trial design limitations
  • Benefit-risk balance concerns
  • Generalizability to real-world patients
  • Unvalidated endpoints
  • Limited data integrity

These uncertainties often arise from issues related to trial design, conduct, analysis, or reporting—such as unvalidated end points, limited long-term data, or approval based on a single trial.

Why This Matters for Prostate Cancer Patients

This research has particular relevance for prostate cancer patients, as the findings come during a period of significant activity in prostate cancer drug development:

Recent Prostate Cancer Approvals:

  • In June 2025, the FDA approved darolutamide (Nubeqa) for metastatic castration-sensitive prostate cancer, showing a 46% reduction in progression risk
  • March 2025 saw the approval of Gozellix (TLX007-CDx), a next-generation PSMA-PET imaging agent for prostate cancer detection
  • The FDA also expanded the indication for Pluvicto (lutetium Lu 177 vipivotide tetraxetan) for PSMA-positive metastatic castration-resistant prostate cancer

The Broader Context: FDA's New Direction

The transparency concerns come as the FDA is taking steps to raise standards for cancer drug approvals. Recent draft guidance emphasizes overall survival as the "gold standard" endpoint, with the FDA recommending companies prioritize overall survival as a primary endpoint where feasible. This guidance follows the return of CBER Head Vinay Prasad, who has previously argued that using surrogate endpoints trades speed for therapeutic uncertainties.

The Communication Challenge

The study authors found that more than 75% of cancer drugs are approved through expedited regulatory programs, the use of which often leaves clinical uncertainties about drug efficacy and safety. While the FDA describes these uncertainties in detail in its benefit-risk assessments, these documents are not widely read by clinicians. Instead, clinicians often rely on journal publications and guidelines.

Additional research published in Health Affairs found that FDA reviewers identified 213 clinical trial uncertainties with new cancer drugs from 2019-2022, with 50% considered important to approval decisions. However, drug labels reported information on only 26% of all uncertainties and 48% of important uncertainties.

What Patients Should Know

  1. Ask Specific Questions: When discussing new treatments, ask your oncologist about:
    • Whether the drug was approved through an expedited pathway
    • What uncertainties exist about long-term benefits and risks
    • How the clinical trial population compared to your situation
  2. Understand Trial Design: Single-arm trials (where everyone gets the experimental treatment) provide less certainty than randomized controlled trials.
  3. Consider the Evidence Level: The study found that drugs with more uncertainties had lower evidence ratings in clinical guidelines.

Recommendations for Improvement

The researchers recommend several steps to address these transparency gaps:

  • Make FDA assessments more accessible: The FDA should make its benefit-risk assessments more accessible and user-friendly
  • Improve reporting standards: Reporting guidelines should consistently require disclosure of key clinical trial uncertainties
  • Better guideline development: Guideline developers should systematically incorporate FDA assessments into their recommendations

Moving Forward

As prostate cancer patients navigate an increasingly complex landscape of treatment options, this research underscores the importance of thorough discussions with healthcare providers about both the benefits and limitations of new therapies. While expedited approvals can bring promising treatments to patients sooner, understanding the associated uncertainties is crucial for informed decision-making.

Sources and Formal Citations

  1. Cherla, A., Wagner, A.K., Wouters, O.J., et al. Reporting of Clinical Trial Uncertainties With New Cancer Drugs in Journal Publications and Clinical Guidelines. JAMA. Published online September 3, 2025. doi:10.1001/jama.2025.13917. Available at: jamanetwork.com
  2. Cherla, A., Woloshin, S., Wagner, A.K., et al. New Cancer Drug Approvals: Less Than Half Of Important Clinical Trial Uncertainties Reported By The FDA To Clinicians, 2019-22. Health Affairs. 2025 Jul;44(7):830-838. doi:10.1377/hlthaff.2024.01134. Available at: https://www.healthaffairs.org/doi/10.1377/hlthaff.2024.01134
  3. U.S. Food and Drug Administration. FDA approves darolutamide for metastatic castration-sensitive prostate cancer. June 3, 2025. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer
  4. Bayer United States. U.S. FDA Approves NUBEQA® (darolutamide) to Treat Patients with Metastatic Castration-Sensitive Prostate Cancer. June 3, 2025. Available at: https://www.bayer.com/en/us/news-stories/metastatic-castration-sensitive-prostate-cancer
  5. FDA Looks To Raise Survival Bar for Cancer Drug Approvals in New Draft Guidance. BioSpace. August 2025. Available at: https://www.biospace.com/fda/fda-looks-to-raise-survival-bar-for-cancer-drug-approvals-in-new-draft-guidance
  6. Dive Into March 2025 FDA Approvals Across Cancer Subtypes. CURE Today. April 2, 2025. Available at: https://www.curetoday.com/view/dive-into-march-2025-fda-approvals-across-cancer-subtypes
  7. Many Uncertainties With New Cancer Drugs Don't Make it to FDA Label, Study Finds. AJMC Evidence-Based Oncology. August 2025. Available at: https://www.ajmc.com/view/many-uncertainties-with-new-cancer-drugs-don-t-make-it-to-fda-label-study-finds
  8. Oncology Drugs Granted FDA Designations in August 2025. Oncology News Central. September 3, 2025. Available at: https://www.oncologynewscentral.com/drugs/info/oncology-drugs-granted-fda-designations-in-august-2025
  9. FDA Approvals in Oncology: April-June 2025. AACR Blog. July 2, 2025. Available at: https://www.aacr.org/blog/2025/07/01/fda-approvals-in-oncology-april-june-2025/
  10. Oncology Drugs Fast-Tracked by the FDA in January 2025. Oncology News Central. February 4, 2025. Available at: https://www.oncologynewscentral.com/drug/oncology-drugs-fast-tracked-by-the-fda-in-january-2025
  11. Reporting of Clinical Trial Uncertainties With New Cancer Drugs in Journal Publications and Clinical Guidelines | Oncology | JAMA | JAMA Network

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