FDA: Novel Trial Design Meetings

Drug sponsors wishing to take part in the FDA’s pilot meeting program to discuss complex innovative trial designs (CIDs) with agency staff may now file meeting requests.

The CID pilot meeting program is for innovative designs that require simulations and for which Type 1 errors — false positive findings — may not be acceptable. It’s also meant to boost innovation by allowing the FDA to share trial designs considered in the program, including designs for drugs the agency has not yet approved.

In an Aug. 30 Federal Register notice, the agency said meeting requests should include key features of the statistical analysis plan, as well as the simulation plan and components of the study design the sponsor believes are non-disclosable.

Sponsors must meet certain requirements to participate in the pilot meeting program. For example, they must have a pre-IND or IND number for the drug(s) that are part of the design proposal, and the design must aim to demonstrate effectiveness of the drug(s) and support their regulatory approval.

The trial cannot be a first-in-human study, and there must be an adequate amount of clinical information available to inform the proposed design. Additionally, the sponsor must reach an agreement with the agency regarding public release of the trial design information.

The agency said it will select requests based on therapeutic need and innovative features of the trial design, “particularly if the innovation may provide advantages over alternative approaches.”

Read the notice here.

FDA to Replace Guidance on Developing New Pain Drugs

FDA Commissioner Scott Gottlieb last week said the agency plans to scrap its existing guidance on developing new pain drugs and replace it with guidances designed to promote development of new opioid alternatives and improve benefit and risk assessments of new opioid drugs in the works.

“Everything is on the table,” Gottlieb said in announcing the move aimed at driving innovation for fresh options to the potent, addictive pain meds. He noted the initiative will include at least four new guidances.

To broaden the range of opportunities, he said the agency will “recommend the study of one or two populations for innovators who wish to pursue a more limited indication for the treatment of specific kinds of pain.”

One guidance, which Gottlieb said “will be out soon,” will share the agency’s latest thinking on how sponsors can show clinically meaningful reductions in opioid use for acute pain.

Another planned guidance will outline information the agency wants drugmakers to provide to help assess benefits and risks of new opioid pain drugs put into development—and update the framework for evaluating the risks of opioid misuse or abuse.

A separate guidance will describe a development path for extended-release local anesthetics that can serve as potential alternatives to oral opioid use, including trials that can support product approval, proper safety and efficacy evaluation methods and clinical pharmacology.

The agency also plans to issue guidance for sponsors of new non-opioid meds that may offer therapeutic alternatives for chronic pain.

Gottlieb said the agency plans to roll out the new guidances in the next six to 12 months.

Sponsors on BP Effects Guidance

FDA draft guidance on assessing a new drug’s impact on blood pressure does not adequately explain the agency’s thinking on the use of smaller clinical trials and should incorporate a more risk-based approach, according to comments from three leading drug sponsors.

Roche noted the logistical difficulties of smaller trials and said it would be hard to design such studies to detect blood pressure effects in the 2 to 3mm Hg range.

Roche also called for a more risk-based approach to potential drug-induced effects on blood pressure and said ambulatory blood pressure monitoring (ABPM) investigations should be reserved “for cause,” that is, “based on mechanism of action, high-risk population or evidence of a blood pressure effect in early emerging data.”

Merck noted that, in trial populations, there are circumstances where assessing pressor effects in the target disease population could be logistically difficult and performing the assessment in a population “akin to” the target population may be more appropriate. It suggested the final guidance should allow sponsors to consider a patient population similar to the intended target population.

In its comment, Novo Nordisk called on the agency to provide more detail on the use of home blood pressure measurements as an alternative to ABPM, noting the ambulatory approach can present logistical challenges due to the required data analysis and equipment involved.

Read the comments here.