FDA Cautions on Use of ‘Bayesian’ Statistics in Complex Trials

September 30, 2019

Sponors of trials using complex innovative designs (CID) should carefully consider the statistical approaches they will use and discuss them with the FDA, a new draft guidance issued last week says.

The benefits and risks of using novel statistical approaches — especially Bayesian analysis — in CID trials must be weighed carefully.

“The use of Bayesian methods can increase the chance of erroneous conclusions,” the agency says, adding that discussions between sponsors and the agency are “critical to the FDA’s evaluation of Bayesian proposals.”

It also warns about leveraging outcome data from the phase 2 to the phase 3 stage by making projections about outcomes, noting that “borrowing the prior data could increase the chance of a false conclusion of effectiveness.”

Comments on the draft guidance are due Dec. 23.

Read the draft guidance here:

ALS Guidance Embraces Regulatory Flexibility to Speed Treatments

Sponsors of treatments for amyotrophic lateral sclerosis (ALS) will benefit from increased FDA regulatory flexibility, according to final guidance released last week.

The agency recognizes that scientific progress has been “particularly lagging” for complex neurological diseases such as ALS, said acting FDA Commissioner Ned Sharpless in a joint comment with Center for Drug Evaluation and Research Director Janet Woodcock. “[W]e stand ready to use the expedited development and approval programs available to help bring new treatments for ALS to patients as quickly as possible.”

The agency suggests decentralizing trials and broadening inclusion criteria to include as many different types of subjects as possible in trials. It also encourages the use of novel technologies for conducting ALS trials, such as wearables and biosensors.

Read the final guidance here:

Patient Advisors Can Expedite Device Trials, FDA Says

The FDA is urging sponsors of medical device trials to involve patient advisors in the design and conduct of their trials, according to a draft guidance released last week.

The guidance defines the term “patient advisors” as “individuals who have experience living with a disease or condition” but who are not study participants themselves.

Companies can work with patient advisors to improve informed consent, follow-up visits, endpoints and patient-reported outcomes. Input from patient advisors also can reduce protocol violations and revisions, and streamline data collection, resulting in better data, the agency says.

The FDA’s goal in issuing this guidance is to help sponsors find ways to combat the challenges and misperceptions involved in patient engagement, including the perception that the agency does not allow patient engagement in the design and conduct of clinical investigations, and patient perceptions that their input is not valued.

Because patient advisors primarily serve in a consulting or advisory capacity, the guidance says, the FDA does not consider these types of activities to “constitute research or an activity subject to FDA’s regulations” and so don’t require IRB approval.

Comments for the draft guidance close Nov. 25.

Read the draft guidance here:

Mass General Develops New Trial Design for ALS

The Sean M. Healy Center for ALS at Massachusetts General Hospital will launch the first clinical trial platform for amyotrophic lateral sclerosis (ALS).

The innovative platform trial, a partnership with biotech company Prilenia, aims to accelerate the development of effective treatments by evaluating three drugs at the same time.

Prilenia’s ALS drug Pridopidine will be the first treatment tested. Two additional compounds will be added to the trial at a later date.

Conflict of Interest Oversight Lacking at NIH, IG Says

The National Institutes of Health does not supervise its grantees’ financial conflicts of interest closely enough, especially when it comes to involvement with foreign entities, according to recent inspector general reports.

While the HHS Office of Inspector General (IG) commended NIH for establishing a database of financial conflict of interest (FCOI) reports, it noted that there is no quality assurance procedure for reviewing the reports before awarding grants. Only 3 percent of NIH’s 2018 grants — totaling $1 billion — went to investigators with FCOI statements on file.

In addition, HHS regulations do not require FCOI statements to identify whether conflicts involve an entity outside the U.S., leaving NIH-funded research open to potential foreign influence, the IG says.

The agency watchdog also took issue with NIH’s oversight of its grantees’ FCOI policies. Of the 1,875 institutions receiving NIH grants in 2018, 1,013 did not post the required FCOI policy on their websites.

The IG reports make several recommendations for improving NIH handling of conflicts of interest, including making periodic quality assurance reviews of its online system, enhancing its FCOI monitoring program to ensure that institutions resolve identified deficiencies and reviewing all grantee websites to ensure that FCOI policies are publicly accessible.

NIH also should “use information regarding foreign affiliations and support that it collects during the pre-award reporting process to decide whether to revise its FCOI review process to address concerns regarding foreign threats,” the IG says.

NIH concurred with all IG recommendations but noted that the institutions that failed to post their FCOI policies in 2018 represent only 4 percent of its grants that year.

Read the IG reports here:

University of Maryland Receives NIH Grant for Flu Vaccine Research

The University of Maryland Center for Vaccine Development and Global Health (CVD) will receive an NIH grant of up to $200 million to develop a universal flu vaccine.

In the first stage of the seven-year grant, the center will use $2.5 million for clinical testing aimed at improving seasonal influenza vaccines and conducting challenge studies for the National Institute for Allergy and Infectious Diseases’ Collaborative Influenza Vaccine Innovation Center (CIVICs) program.

Bayer Joins AI Data Management Collaboration

Bayer has joined the Life Sciences Cloud Coalition, which uses Accenture Life Sciences’ artificial intelligence platform for clinical data collection and management.

Accenture’s Intient platform uses a cloud-based technology developed by Oracle to collect internal and external clinical data in a single data management system.

The coalition, which enables collaboration among biopharmaceutical companies, also includes Pfizer, Eli Lilly, Merck, Novo Nordisk and GlaxoSmithKline.

Elligo Partners with Canadian Walmart Clinics

Elligo Health Research is partnering with Jack Nathan Health in Canada to provide clinical research as a care option for its Walmart clinics.

The partnership expands on Elligo’s research network, with an added $20 million in funding to connect physicians and their patients to clinical trials. The partnership will draw on the two million patients the Walmart clinics see annually.

WCG KMR Opens New Trial Cost Benchmark Study

Enrollment in the WCG KMR 2019 Clinical Trial Cost Study is now open to pharma companies.

WCG KMR collects data validated directly with clients to ensure integrity in the results. Findings from the study will be presented to senior leadership teams of participating organizations.

To apply to participate in the study, click here: