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# 2 Guidances to Help Modernize Clinical Trials
- URL: https://www.fdaweb.com/2-guidances-to-help-modernize-clinical-trials/
- Published: 2018-10-15T12:00:00.000Z
- Updated: 2026-09-15T00:38:12.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5142580

As part of its continuing push to modernize clinical trials, FDA 10/15 released two guidance documents to provide greater clarity and recommendation for drug developers. The first is a draft guidance, [Hematologic Malignancies: Regulatory Considerations for Use of Minimal Residual Disease in Development of Drug and Biological Products for Treatment](https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM623333.pdf?ref=fdaweb.com), which assists sponsors planning to use minimal residual disease (MRD) as a biomarker in clinical trials for drugs/biologics to treat specific blood cancers. MRD is a general measure of tumor burden, and depending on the clinical setting, it may reflect a patient’s response to treatment or it may be used as a prognostic tool to assess the risk of future relapse, according to the agency. “As such, it may be considered for use to enrich clinical trial populations, or to guide allocation into specific treatment arms in clinical trials and could be developed as a potential surrogate endpoint,” the guidance says. “With the advent of newer technologies, such as the recently authorized ClonoSEQ assay, a next generation [sequencing](https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm622004.htm?ref=fdaweb.com)\-based test that allows for the detection of MRD at lower levels of disease, MRD assessments may be useful in clinical trials and have the potential to expedite product development.”  

The second is a final guidance, [Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease](https://www.federalregister.gov/documents/2018/10/16/2018-22437/guidance-developing-targeted-therapies-in-low-frequency-molecular-subsets-of-a-disease?ref=fdaweb.com), which deals with treatments that address the underlying molecular changes (e.g., genetic variants) that often cause or contribute to diseases, including uncommon, or rare molecular changes that are present in a small subset of patients. The guidance discusses an approach for drug developers to enroll patients based on rare variants into clinical trials for targeted therapies when reasonable scientific evidence suggests the drug could be effective in patients with these genomic findings. It also discusses the evidence needed to demonstrate effectiveness for a variety of molecular subsets within a particular disease. “This approach could lead to more consistent development and approval of targeted therapies for patients who are likely to benefit from them,” the document says.

  
The agency says that understanding a disease’s molecular basis has paved the way for certain targeted therapies. “For instance, the FDA has already approved a cancer therapy based upon whether the patient’s tumor shows a specific biomarker, rather than based upon the tissue of origin of the tumor — a so-called ‘tissue agnostic’ indication for the drug,” it says. FDA was referring to a 2017 accelerated approval for [Merck’s Keytruda](https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm560040.htm?ref=fdaweb.com). “We think innovative approaches have the potential to increase the likelihood of finding viable treatment options for those with less common mutations. This is especially true when paired with innovative clinical trial approaches, such as those using a master protocol, where the efficacy and safety of a number of drugs can be studied at the same time, each targeting a different genetic subset of a type of cancer.”