Briefs

Gottlieb Calls on Clinical Trial Operators to Find Ways to Enroll More Women

May 21, 2018

Clinical trial sponsors must step up their efforts to address underrepresentation of women among trial subjects, FDA Commissioner Scott Gottlieb said Wednesday during a meeting in White Oak, Maryland, to commemorate National Women’s Health Week. He cited the FDA-led Decadal Review that studied clinical trial efficacy and safety by sex for 34 drugs and five cardiovascular disease indications over a 10-year period from 2005 to 2015. The study analyzed the inclusion and exclusion criteria for five of the trials to get a clearer picture of whether such criteria affected subject enrollment. The results, Gottlieb said, indicated there were minimal gender differences in drug profiles, and that while women were well-represented in trials for hypertension and atrial fibrillation drugs and overrepresented for pulmonary arterial hypertension (PAH) drugs, they were underrepresented in trials for heart failure, acute coronary syndrome and coronary artery disease drugs. “These findings support the need for the FDA to issue a call to action to clinical investigators. In this case, the bottom line was that more work is needed to identify factors leading to under-participation of women in cardiovascular clinical trials in certain areas, notably heart failure, coronary artery disease and acute coronary syndrome,” Gottlieb said. One possible reason for under-enrollment of woman subjects may be of advanced age at disease onset, Gottlieb said, indicating sponsors should look into prevalence-adjusted representation of women in cardiovascular trials across relevant age categories. On the other end of the spectrum, sponsors are often hesitant to expose new or expectant mothers, who tend to be younger women, to experimental drugs, which can be a major barrier to developing drugs for conditions that are prevalent in younger women. To correct this, the FDA is using the Medication Exposure in Pregnancy Risk Evaluation Program to model pregnant women’s responses to drugs at reduced risk, he said. Other agency efforts to remedy gender parity issues include the agency’s Diverse Women in Clinical Trials Initiative consumer awareness campaign and a planned series of webinars on recruitment and retention of women in clinical trials. The agency is also conducting several research initiatives to aid in its regulatory decision-making with regard to sex differences, he said.

CTTI Planning Recommendations on Investigators, Decentralized Trials and Mobile Technologies

May 7, 2018

The Clinical Trials Transformation Initiative is developing several new sets of recommendations relating to clinical trials — on the qualification of investigators, the potential legal and regulatory hurdles to decentralized trials and obstacles to incorporating mobile technology, according to its 2017 annual report. In the report marking the organizations 10th anniversary, CTTI also aims to develop toolkits personalized to stakeholders to help with adoption of its recommendations and says it will share case studies with the clinical research community to show how the resources can be applied to improve processes and outcomes. The initiative issued five new sets of recommendations last year including: developing novel endpoints generated by mobile technology; making registries into reusable platforms for conducting clinical trials; providing for pregnancy testing in clinical trials; strengthening pediatric trials in antibacterial drug development; and strengthening the investigator site community. Read the CTTI annual report here: https://www.ctti-clinicaltrials.org/news/ctti-releases-2017-annual-report-one-decade-impact-one-vision-ahead.

Novartis Announces Real-Time, Self-Reported Data-Based App for Ophthalmic Trials

April 30, 2018

Novartis has launched an ophthalmic digital research app that will allow researchers to monitor disease progression through self-reported patient data. The app, FocalView, collects real-time, voluntarily disclosed data from consenting patients, which will allow Sponsors to adapt clinical trial design to patients’ routines. The goal is to eliminate some of the most common obstacles to trial participation and increase practical understanding of ophthalmic diseases. The company is planning to test the app in a prospective, non-interventional study to determine its use for evaluating visual function such as acuity and contrast sensitivity. “Because patients with eye diseases are often not as mobile, FocalView has the potential to offer tremendous benefit for the ophthalmic community and for researchers looking to develop better treatments for these patients,” said Mark Bullimore, dean of the Southern California College of Optometry, Marshall B. Ketchum University, who served as medical advisor for the creation of the app.

FDA to Launch Pilot Program on Model-Informed Drug Development

April 23, 2018

The FDA announced a new pilot program in which drug sponsors can meet with agency officials to discuss strategies for model-informed drug development (MIDD) to make their clinical trials more efficient and increase the chances of regulatory approval. Under the pilot, each applicant whose proposal is approved will receive two meetings with the relevant agency center to discuss approaches to applying MIDD, which uses quantitative analysis to assess the risk-benefit profile of in-development drug products. “The goal of the early meeting discussions granted under this pilot program is to provide advice on how specific, proposed MIDD approaches can be used in a specific drug development,” the FDA said. The agency plans to accept two to four meeting requests per fiscal quarter from the fourth quarter of 2018 to the fourth quarter of 2022. Because of the limited number of meeting slots, the agency will prioritize requests that focus on dose selection/estimation, clinical trial simulation and predictive or mechanistic safety evaluation. Applicants should be drug or biologic manufacturers with a relevant IND or pre-IND number. The meeting requests should include the product name, application number, chemical name/structure and proposed indications or context of product development. Applicants should also include a brief overview of the purpose and objectives of the potential meeting, proposed MIDD approaches for the product and a list of issues for discussion with the agency. The submission package should also address drug development issues such as dosing, safety predictions or clinical trial design and the proposed MIDD approach. The pilot will be administered jointly by CDER’s Office of Clinical Pharmacology and CBER’s Office of Biostatistics and Epidemiology. Read the Federal Register notice here: www.fdanews.com/04-16-18-Pilot.pdf.

FDA Recommends Early, Pre-Approval Trials in Pediatrics for Systemic Dermatitis Drugs

April 16, 2018

The FDA published a new draft guidance outlining how early Sponsors should incorporate pediatric patients, and relevant age groups, for systemic therapies for atopic dermatitis (AD). The agency previously recommended that Sponsors submit pre-approval data on the use of topical products, but did not recommend pediatric studies of systemic drugs until after adult approval. The new draft guidance recommends Sponsors initiate pediatric studies early in development, typically after obtaining initial evidence from early-phase adult studies. In addition, Sponsors should discuss the specifics of their pediatric programs with the FDA as early as possible, as pediatric study plans are required to be submitted within 60 days after an end-of-Phase II meeting. The FDA said it is important to study all relevant age groups, including children younger than two years of age. A sequential approach may not be needed, except for safety concerns, technical issues or the need for information from older subpopulations to inform further study designs. Juvenile animal toxicity studies should also be considered before enrolling human participants. If approved, Sponsors should provide as much information as possible when labeling in regard to pediatric use. The agency said it is also planning a separate guidance to address the technical aspects of drug development for pediatric patients with AD. The draft guidance is available here: www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm603702.pdf.

FDA Outlines Considerations for Enrolling Pregnant Women in Clinical Trials

April 9, 2018

The FDA published a new draft guidance on the scientific and ethical considerations for including pregnant women in clinical trials, telling sponsors that data are needed to inform safe and effective treatment during pregnancy, and that it is appropriate to enroll pregnant women in certain situations. The agency said it considers it ethically justifiable to include pregnant women in clinical trials when adequate nonclinical studies have been completed, and when the trial holds the prospect of direct benefit to the women and/or the fetus that cannot be obtained by any other means. In the postmarket setting, an established safety database in nonpregnant women should be available, and inclusion should be allowed when efficacy cannot be extrapolated or safety cannot be assessed through other study methods.

Veeva and Six CROs Form New Industry Data Standards Group

April 2, 2018

Veeva Systems and six large contract research organizations formed a new technology standards group focused on improving trial collaboration with sponsors. The group — dubbed Align Clinical CRO — includes ICON, Medpace, Pharmaceutical Product Development, PRA Health Sciences, Syneos Health and UBC. “There is tremendous potential to enhance clinical trial execution with common technology standards that benefit the entire industry,” said Henry Levy, president of Align Clinical CRO, which aims to reduce operational costs and run trials faster. “By creating a vehicle for CROs to collaborate and share actionable insight with sponsors, we can improve operational delivery and streamline the increasingly complex trial process,” said Syneos Health CIO Rachel Stahler. The group expects to first deliver a pre-competitive operational data exchange standard, to facilitate information sharing between sponsors and CROs, including definitions related to trial operations, key metrics and milestones. The standard will be posted for public review and input before adoption, the group said. “This is the first time CROs are coming together to make this commitment to transform clinical trials across our industry, and we are excited to be part of this effort,” said Michael Brooks, executive vice president of product registration at PRA Health Sciences. “This shows our mutual commitment to make the drug development process more efficient and to help bring needed therapies to market more quickly.”

House Republicans Pass Right-to-Try Bill

March 26, 2018

The House passed its version of federal right-to-try legislation, sending it for reconsideration by the Senate, which passed a similar bill last August. The bill, H.R. 5247, had failed to garner enough votes on the floor last week to fast-track the bill under suspension of the House rules. Republicans that favor the legislation said they believe terminally ill patients, that have exhausted all other treatment options, should be able to try unproven therapies as a last resort. “For those patients caught between the traditional drug approval delays, a clinical trial process for which they do not qualify, and limited time, this right-to-try establishes the freedom for patients to try therapies in situations where the benefits far outweigh the risks,” said bill sponsor Rep. Brian Fitzpatrick (R-Pa.). Most Democrats opposed the bill, arguing that it would hinder the FDA’s oversight of investigational treatments — and contending that patients already have a program through which they can request access to experimental treatments. In addition, four former FDA commissioners — Robert Califf, Margaret Hamburg, Mark McClellan and Andrew von Eschenbach — as well as over 80 patient advocacy organizations opposed the bill because it would remove agency protections from the process.

IBM Watson Helps Increase Cancer Trial Enrollment

March 19, 2018

In the span of nearly a year, Mayo Clinic’s use of IBM’s Watson computing system for matching patients to clinical trials helped increase enrollment by an average of 80 percent in studies of systemic therapies for breast cancer. Over 11 months, the time needed to screen an individual patient for clinical trial matches also fell when compared to traditional manual methods, they said in a joint press release. In July 2016, Mayo began using the system with a team of screening clinical research coordinators in its ambulatory practice for patients with breast cancer. “This has enabled all patients to be screened for all available clinical trial opportunities,” said Mayo oncologist Tufia Haddad, physician leader for the Watson matching project. The two organizations also plan to expand training and use of the system, including using Watson in additional cancer types, as well as other aspects of cancer therapy, such as surgery, radiation and supportive care. Currently, the system is trained to support clinical trial matching for breast, lung and gastrointestinal cancers.