Briefs

Study: Clinical Trials for Psoriasis Drugs Don’t Match Real-World Outcomes

June 25, 2018

Clinical trials for psoriasis drugs fail to reflect their real-world safety and efficacy, according to the findings from an observational study by a team of U.K. researchers reported in JAMA Dermatology. The researchers studied what proportion of patients with psoriasis who were taking a biologic and were on the British Association of Dermatologists Biologics Intervention Register (BADBIR) would have been eligible for the pivotal licensing trials of biologics for psoriasis. In their study of 7136 patients, those identified as ineligible for clinical trials had lower effectiveness and higher rates of serious adverse events while receiving biologic therapy in the first 12 months compared with patients identified as eligible. The findings aligned with a 2012 study that found a disparity between real-world data and clinical trials for dermatological drugs. The new study suggests that clinical trial protocols and the reasoning behind them need more transparency, according to the authors who say sponsors should consider alternative prelicensing study designs or postmarket studies set at the time of licensing. Read the full article here: https://jamanetwork.com/journals/jamadermatology/article-abstract/2674865.

NEJM Retracts Five Studies, Revises A Sixth, After Trial Sampling Errors Discovered

June 18, 2018

The New England Journal of Medicine has retracted five separate papers and reissued a sixth with corrections, nearly a year after an anesthesiologist raised public questions about whether the volunteers in each of the studies had truly been randomly assigned to different treatments. British anesthesiologist, JB Carlisle, built a computer model that helped him analyze sampling in clinical trials. After examining nearly 5,100 trials, he claimed that two percent of them had used nonrandom sampling when researchers claimed the opposite. Carlisle flagged studies in eight journals, 11 of them having been published in the New England Journal. On June 13, the Journal announced that it was retracting five of those studies. A sixth — a 2013 study on the benefits of the Mediterranean diet — was retracted but republished after researchers “reanalyzed” their data.

Effective Date for Medical Device Clinical Trials Rules Included in HHS Regulatory Agenda

June 11, 2018

HHS will publish its semi-annual regulatory agenda on Monday, and it includes a February 21, 2019, effective date for a new rule that will require that data from medical device studies conducted outside the U.S. be gathered in accordance with good clinical practices, including review and approval from an independent ethics committee and well-documented informed consent. The agency’s final rule applies to data intended to support IDE applications, 510(k) submissions, and de novo classification requests, as well as applications for premarket approval, product development protocols and humanitarian device exemptions. It also applies to bench and in vitro diagnostic studies of de-identified specimens. The new mandates would replace the current pre-market approval regulations that require clinical studies to conform to the Declaration of Helsinki or the law of the country where the research is conducted, whichever carries greater protection for human subjects, the FDA said. The rule does not apply to all clinical investigations performed overseas, but only sets criteria for FDA acceptance of data used to support device marketing applications or submissions.

Trump Signs Right-to-Try Into Law

June 4, 2018

President Trump on Wednesday signed into law the Right-to-Try Act establishing a pathway for terminally ill patients to use non-FDA-approved drugs, calling the legislation “great for the people” and a “fundamental freedom,” but it was a castoff remark he made about lower drug prices that had everyone talking. Referring to the legislation, Trump thanked HHS Secretary Alex Azar and FDA Commissioner Scott Gottlieb at the signing ceremony and also credited Gottlieb for his efforts to shorten the development and approval process. “You have a lot of things in the wings that frankly if you moved them up, a lot of people would have a great shot,” he said, adding that “hundreds of thousands of lives” would be saved by the new legislation. The law allows terminally ill patients who have exhausted all other options to try experimental treatments that have not yet received FDA approval. Eligible treatments must have completed a Phase I trial, be in the process of active development, and be the subject of an NDA, BLA or IND. The new law has its critics among industry and patient advocacy groups with reservations about its potential impact on patient safety. The Association of Clinical Research Organizations came out strongly against the bill’s passage, calling the legislation “deeply flawed.” ACRO argued the bill does not go far enough to protect patients and “compromises the clinical trial process [and] undermines the FDA’s authority to assess safety and effectiveness.” After several iterations, the version of the bill that finally passed is “devoid of all patient protections” and “does not set a standard for informed consent, has a much broader definition of eligibility and contains vastly weaker reporting requirements,” according to the National Organization for Rare Disorders. “Thus, not only will this legislation be ineffective, as all Right to Try laws are, it will also present a danger to the many patients we represent.” In a statement following the signing ceremony, Gottlieb said the FDA recognizes “the important balance between making sure patients have the assurances Congress intends, while enabling timely access to promising treatments in these devastating circumstances.” He said the agency will “implement this new law consistent with these longstanding values.” During the ceremony, Trump also made a side remark that unnamed major drugmakers would announce “voluntary massive drops in prices” in “two weeks” adding that “for the first time ever in this country, there will be a major drop in the cost of prescription drugs.” At the White House daily press briefing Wednesday, Press Secretary Sarah Sanders said the White House could not provide further details, “but we do expect some specific policy pieces to come out on that soon.” Industry groups appeared puzzled as to what the president was referencing, although the Association for Accessible Medicines responded to the remark in a tweet, saying it looks forward to continue working to reduce prices and out-of-pocket costs. PhRMA declined to comment and BIO did not respond to a comment request.

Elligo Acquires Patient Identification Platform from ePatientFinder

May 29, 2018

Elligo Health Research announced Thursday that it was buying ePatientFinder’s technology platform, a move that Elligo officials said will “streamline patient identification and feasibility through automation using electronic health record data.” ePatientFinder has claimed its Clinical Trial Exchange was the “first and only” technology platform that linked up doctors, clinicians, sponsors and EHR providers. The platform is the largest of its kind and Elligo sees is acquisition as “a strategic opportunity … to expand our technology and network growth capabilities,” the company said in a news release. The deal comes just two months after Elligo announced that it had raised $16 million from venture capitalists to continue its goals of reaching the 97 percent of physicians who don’t regularly participate in clinical trials. Terms of the deal were not disclosed.

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.