FDA Finalizes Adaptive Clinical Trial Design Guidance

The FDA has issued a final guidance on adaptive clinical trials, reworking its subsection on Bayesian methods and clarifying the extent of pre-specification required for the rules governing adaptations.

The revised Bayesian subsection explains the agency’s recommendations on applying that approach, including simulations, predictive statistical modeling and borrowing of information from external sources.

In draft guidance comments, Pfizer and other drug companies noted the rising use of Bayesian designs in their feedback to the agency and sought further explanation of the agency’s thought processes on that topic, including the treatment of Type 1 errors and simulations. Overall, 21 comments were received on the draft guidance.

The final guidance also explains the importance of completely specifying the adaptive design’s details before trial launch. In addition, it cross-references advice given in its September draft guidance on complex innovative trial designs.

The guidance focuses on the design, running and data reporting of adaptive clinical trials, studies designed to enable sponsors to react to evidence while it’s being generated in an ongoing study and enact design changes planned in advance. While the guidance mainly deals with trials that support safety and efficacy, it also pertains to early-phase, exploratory and post-market trials, the agency said. The final guidance is largely the same as the agency’s 2018 draft guidance.

“Adaptive designs can provide a variety of advantages over non-adaptive designs. These advantages arise from the fundamental property of clinical trials with an adaptive design: they allow the trial to adjust to information that was not available when the trial began,” the FDA said.

Read the final guidance here: www.fdanews.com/12-02-19-AdaptiveDesigns.pdf.

Senate HELP Committee Advances Hahn’s Nomination to Floor

The Senate committee on Health, Education, Labor and Pensions voted 18-5 on Tuesday to advance Stephen Hahn’s nomination as FDA commissioner to the Senate floor.

Committee Chair Lamar Alexander (R-Tenn.), who voted in Hahn’s favor, called him “exactly the type of nominee that we should want” to lead the agency.

However, ranking member Sen. Patty Murray (D-Wash.), who voted against Hahn’s confirmation, told the committee that she was “just not convinced” that Hahn is the right person for the job.

Sen. Mitt Romney (R-Utah), who ultimately voted for Hahn, expressed a similar sentiment, saying he was voting with “some degree of concern” over Hahn’s position on vaping and e-cigarettes. Despite his concerns, Romney described Hahn as a “solid professional with the right instincts and the right record.”

Five former FDA commissioners previously backed Hahn’s nomination.

Alexander urged the full Senate to confirm Hahn as FDA commissioner “before the end of the year.”

FDA Recaps New Drug Approvals in 2019

The FDA continued to lead the world in new molecular entity approvals in fiscal 2019, according to a senior official in the Office of New Drugs.

The agency approved 45 NMEs in FY 2019, approximately half of which were orphan drugs, said OND’s Deputy Director of Operations Khushboo Sharma. Of those with orphan status, more than half were for oncology or oncologic imaging.

Speaking Tuesday at the FDA/CMS Summit in Arlington, Va., Sharma highlighted some notable approvals this year, including Vertex’s cystic fibrosis treatment Trikafta (elexacaftor/ivacaftor/tezacaftor), the first triple combination therapy for CF patients with the most common gene mutation, and Janssen’s treatment-resistant depression spray Spravato (esketamine), among others.

FDA Issues Draft Guidance for Developing Hemorrhoids Treatments

The FDA has recommended using increased patient input in a new draft guidance on developing corticosteroid hemorrhoid treatments.

The guidance calls on sponsors to select patient-reported outcome (PRO) instruments that will measure what patients say are their most troublesome symptoms. The FDA encouraged sponsors to use existing PRO instruments rather than develop new ones.

Comments on the draft guidance are due by Feb. 7, 2020.

Read the draft guidance here: https://bit.ly/34XEr9x.

FDA Issues Guidance on Bladder Pain Syndrome Trial Designs

Trials for interstitial cystitis and bladder pain syndrome (IC/BPS) should include patients with at least a six-month history of constant bladder pain, according to a new draft guidance issued by the FDA.

The guidance recommends improvement of both bladder pain and urinary tract symptoms as a primary endpoint. The agency also says that using a single primary effectiveness endpoint may be appropriate, for example, if the drug is not expected to improve lower urinary tract symptoms.

Comments on the draft are due by Feb. 3.

Read the draft document here: https://bit.ly/33P9Mty.

Partnership Launches Database for Parkinson’s Disease

The Accelerating Medicines Partnership (AMP) for Parkinson’s disease has launched a portal to help researchers study the biologic data of nearly 4,300 Parkinson’s patients.

The portal will include data on patient samples of cerebrospinal fluid, RNA, plasma, and DNA.

The AMP is a joint effort of the National Institutes of Health and the FDA, industry and nonprofit organizations.

Headlands Research Acquires Six Sites to Improve Diversity

Headlands Research is aiming to increase the number of ethnically diverse subjects that it includes in clinical trials by acquiring six sites across the U.S. and Canada in what it sees as diverse epicenters.

The organization’s recent acquisition includes Centex Studies in Houston and McAllen, Texas, and Lake Charles, Louisiana, Clinical Research Atlanta, with facilities in Stockbridge and Griffin, Georgia, and Okanagan Clinical Trials, which adds a site in Canada, located in Kelowna, British Columbia.

Novartis Acquires the Medicines Company for Heart Treatment

Novartis has acquired the Medicines Company for $9.7 billion for its drug inclisiran for cardiovascular disease, with the transaction slated to be complete by the first quarter of 2020.

Inclisiran is currently in a phase 3 trial with 15,000 participants testing cardiovascular morbidity and mortality benefits.

Pakistan Publishes Its First Clinical Trials Guidelines

The first edition of guidelines for managing clinical trials in Pakistan has been issued by the country’s Drug Regulatory Authority.

The guidelines describe the requirements, procedure for submission, review, evaluation and approval of applications for conducting trials and requirements for bioethics committees to protect human research subjects.

Pakistan is also creating a clinical trial registry that will list all trials that have been approved.

Read the guidelines here: https://bit.ly/2DHKkfd.

EC Updates Q&A Document on Clinical Trial Regulations Overhaul

As the European Commission closes in on overhauling its clinical trial regulations, it has updated a 12-part Q&A document for sponsors and investigators that is aimed at helping explain the new regulations.

The latest update to the Q&A document answers three questions about the details of running a trial in the European Union. The new regulations are slated to take effect early next year.

Read the document here: https://bit.ly/34Qyuvd.

UK Hospitals Connect With AI Learning for Clinical Trials

The first phase of a collaboration between Kings College of London, software companies and hospitals in the UK will allow researchers to draw on a pool of real-world clinical trial data as large as a third of the population of the city of London.

Kings College London Medical Imaging and AI Centre for Value Based Healthcare and two AI research and software companies, NVIDIA and Owkins, are teaming up to build a dataset spanning information from four hospitals. It hopes to add 12 more hospitals soon.

The network will also ensure the protection of patients’ privacy through an AI technique called federated learning, which allows a machine to learn interconnectivity between various entities without requiring them to directly reveal and share sensitive data.