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# CDER Officials Plug ‘Master Protocols’ for Precision Medicine
- URL: https://www.fdaweb.com/cder-officials-plug-master-protocols-for-precision-medicine/
- Published: 2017-07-10T12:00:00.000Z
- Updated: 2026-09-14T22:32:59.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5139085

CDER officials are advocating for more use of master protocols for “precision medicine” trials to evaluate targeted therapies. Writing in a 7/6 online *New England Journal of Medicine* [article](http://www.nejm.org/doi/full/10.1056/NEJMra1510062?ref=fdaweb.com), Center director **Janet Woodcock** and Office of Biostatistics director **Lisa LaVange** say the move to such protocols is needed because the “standard approach to generating this evidence — a series of clinical trials, each investigating one or two interventions in a single disease — has become ever more expensive and challenging to execute.”

A master protocol “may involve direct comparisons of competing therapies or be structured to evaluate, in parallel, different therapies relative to their respective controls,” the officials write. “Some take advantage of existing infrastructure to capitalize on similarities among trials, whereas others involve setting up a new trial network specific to the master protocol. All require intensive pretrial discussion among sponsors contributing therapies for evaluation and parties involved in the conduct and governance of the trials to ensure that issues surrounding data use, publication rights, and the timing of regulatory submissions are addressed and resolved before the start of the trial.”

The article examines two recent master protocols — I-SPY 2 and Lung-MAP. I-Spy 2 is an exploratory-phase platform trial designed to investigate new treatments for biomarker-identified subtypes of early-stage breast cancer in the context of neoadjuvant therapy. Under this protocol, various drugs are tested as neoadjuvant treatments, which allows the investigators to determine the primary outcome, a pathological complete response of the tumor at surgery, without having to wait for years, the article says.

Lung-MAP is a phase 2–3 master protocol involving rigorously defined advanced squamous non–small-cell lung cancer. It uses a common biomarker screening platform to classify patients into genetic subgroups and is designed to evaluate each targeted therapy independently of the others, the article says. “Patients qualifying for more than one subgroup are randomly assigned to subgroups in such a way that the groups for biomarkers with lower prevalence receive more patients (i.e., the probability of being assigned to a given subgroup is inversely proportional to biomarker prevalence),” the CDER authors write. “Patients whose biomarker signatures do not fall into any of the defined subgroups are assigned to the no-match subgroup, thus allowing more screened patients to participate. Four targeted therapies and one therapy for the no-match subgroup were identified for evaluation versus the standard of care in five independent substudies, each using a phase 2–3 seamless design with progression-free survival and overall survival, respectively, as end points.”

  
The CDER officials note that master protocols “come in different sizes and shapes but share many commonalities. All require increased planning efforts and coordination to satisfy the objectives of different stakeholders. Innovative design elements help ensure that maximum information is obtained from the research effort, and the infrastructure required for implementation increases data quality and trial efficiencies, as compared with those in stand-alone trials. If designed correctly, master protocols can last many years, even decades, with innovations from the laboratory translating quickly to clinical evaluation. As the targets for new drugs become more and more precise, there is no alternative but to move forward with these coordinated research efforts.”