In comments on the agency’s expedited programs draft guidance, PhRMA and BIO say a decision about the relevant standard of care is needed earlier in the development process; groups call for more flexibility on accelerated approval than is suggested in the guidance and identify several issues involving breakthrough therapies that need more clarity.

In its desktop reference guidance on the four expedited regulatory pathways, FDA broadens its view of when an investigational drug fills an “unmet medical need” and guides sponsors through the use of intermediate clinical endpoints as a basis for accelerated approval.

FDA officials are enthusiastic about broad, multi-agent cancer trials built on the I-SPY model. For sponsors, the trials mean less control over the development path and ultimate value proposition for the therapy—but may have important benefits on defending high prices for truly effective new therapies.