Tufts CSDD: Clinical Trial Startup Process Takes Longer Than 10 Years Ago

March 12, 2018

The process of selecting clinical trial sites and launching studies, beginning with site identification and ending with study start-up completion, takes an average of 31.4 weeks for Phase II and III studies — a full month longer than the average seen 10 years ago, according to a survey conducted by the Tufts Center for the Study of Drug Development.

Between 30 and 40 percent of 590 sponsors and CROs said they were somewhat or completely unsatisfied with their processes for site initiation, according to the study. Respondents reported that 61 percent of total cycle time was associated with study start-up activities such as contract and budget negotiations.

Tufts researchers found the widest variations among respondents in site identification cycle times, indicating “highly inconsistent practices,” the report said. Nearly three in 10 sites were new, with no prior history of working with a sponsor or CRO.

Tufts CSDD senior research fellow Mary Jo Lamberti, who led the analysis, said drugmakers are trying to improve the timeliness of the site initiation process.

Sponsors are investing in technology and working to make contracting and budgeting negotiations — which can be a significant drag on the process — more efficient, Lamberti told CWWeekly.

“It’s happening, but it’s just not happening fast enough,” she said.

Another potential solution, Lamberti said, is pooling data from clinical sites to counter the siloing of data common among drug manufacturers. Sharing information with sites early on to assess study feasibility could enhance the site selection process, according to the Tufts report.

Tufts researchers found that CROs are more efficient than drug sponsors, completing initiation an average of 5.6 weeks faster for repeat sites and 11 weeks faster for first-time sites. This was “very telling because there isn’t a lot of research out there comparing cycle times between sponsors and CROs,” Lamberti said.

CROs make more use of advanced technology solutions for the study initiation process than drug sponsors, according to Tufts researchers, with 47 percent of CROs saying they used clinical trial management systems compared to only 28 percent of sponsors. More than half of sponsors still rely on spreadsheets, compared to just under one-third of CROs.

In addition, 10.9 percent of initiated sites are never activated — a constant figure over the past 20 years, according to Tufts — with sites being managed by CROs being activated more often.

More information can be found at http://csdd.tufts.edu/.

By Zack Budryk

CTTI Investigates Barriers to Conducting Pediatric Antibacterial Clinical Trials

March 12, 2018

Pediatric antibacterial drug trials currently account for less than one percent of all interventional and observational pediatric studies registered on ClinicalTrials.gov between October 2007 and September 2015, or only 82 out of 12,703.

According to a series of surveys conducted by the Clinical Trials Transformation Initiative, three of the four major barriers identified by respondents were related to parental involvement and consent.

They included obtaining consent when there is evident disagreement between two parents, parental concerns about the number of blood draws and invasive procedures required by the study protocol. Many parents are reluctant to give consent when they see no direct benefit for their child in a clinical trial and are happy with current care, one respondent said.

Interviews with parents found that each aspect of a study, from initial explanations to reporting the final result, can affect willingness to provide consent. Establishing trust and empathy, as well as providing clear transparency on any risks and benefits, were key decisionmaking factors, CTTI said, describing how parents’ priorities must be incorporated early into trial design for accrual to be successful.

All survey participants strongly preferred to hear about a clinical trial opportunity first from their child’s own pediatrician or from a doctor caring for them in the hospital — rather than being cold-called by a researcher or a stranger. In addition, being approached too soon or too often can be a detriment, such as during the first few days after birth, in the case of premature newborns in neonatal intensive care.

The remaining barrier related to overly narrow inclusion and exclusion recruitment criteria, including prerequisites disallowing the use of other antibacterial drugs prior to enrollment.

Additionally, finding study coordinators with sufficient experience was a significant challenge, with one respondent recommending long-term staff support to help avoid constantly training new staff for each trial.

CTTI’s study identified several recommendations to help facilitate more studies. For example, pediatric trial networks can facilitate development and eliminate the need for startup with each new trial, as well as help standardize site resources and funding.

Another main factor was the ability to recruit study participants directly from the investigators’ own practice, the surveys found. Having dedicated staff available to enroll patients in inpatient studies with little advance warning, potentially 24 hours a day, was described as a major benefit.

Established referral systems, interdisciplinary collaborations and access to the hospital inpatient database were all listed as crucial for recruitment, and supporting the buy-in of other practitioners for their pediatric patients to enroll.

—by Conor Hale @conorhale

Free Online Transparency Tool Tracks Clinical Trials Reporting Compliance

March 5, 2018

The FDAAA TrialsTracker, an online tool that charts whether individual sponsors report their study results on ClinicalTrials.gov in compliance with federal laws and regulations, launched Feb. 19. The data transparency project was developed by the University of Oxford’s Evidence-Based Medicine DataLab, and is available to the public.

Updated daily, the online tool also calculates the amounts the federal government could fine for noncompliance — although, to date, this number remains at $0, according to the tracker.

“In the absence of formal sanctions from the FDA and others, we argue tools such as ours — providing live data on trial reporting — can improve accountability and performance,” the developers wrote in a prepublished paper outlining the methods and results of the tracker.

“In addition, our service helps sponsors identify their own individual trials that have not yet reported results: we therefore offer positive practical support for sponsors who wish to ensure that all their completed trials have reported,” they wrote. Sponsors can immediately improve their ratings by reporting their results, as opposed to more static, academic publications on clinical trial transparency.

To date, 116 of 131 trials have reported their results, amounting to 88.5 percent in compliance. According to the tracker, the U.S. government could levy fines against the 15 overdue sponsors totaling just north of $1.2 million. The database also allows a search of more than 15,000 currently ongoing clinical trials.

The ClinicalTrials.gov reporting requirements began with 2007’s FDA Amendment Act, and were later expanded by an NIH final rule that came into effect in January 2017, encompassing 42 CFR Part 11. Although sponsors are required to disclose results for applicable clinical trials within one year of their primary completion date — regardless of the product’s approval status — legal deadlines have begun to pass unfulfilled, as of January of this year.

Applicable trials include interventional studies of FDA-regulated products outside of Phase I or device feasibility testing. The studies include at least one U.S.-based site, initiated after Jan. 18, 2017. The FDA may fine sponsors up to $10,000 for each day results are not submitted past the deadline.

The tracker lists a study as due to report results after one year plus 30 days, to allow for reasonable delays in processing by ClinicalTrials.gov. The 30 days also represents the timeline for notification of missing results before being fined, the developers wrote. In addition to the FDAAA tracker, Oxford’s EBM DataLab has built an automated platform to monitor European Union reporting compliance, which is currently undergoing peer review.

The tracker is available here: fdaaa.trialstracker.net/. 

—by Conor Hale @conorhale

Early Chart Reviews Can Provide Steady Flow of Potential Study Subjects, Experts Say

February 26, 2018

Beginning chart reviews before initiating a site can generate a list of prequalified candidates for outreach — and give sponsors the chance to examine the study’s inclusion and exclusion criteria, and their potential to cause enrollment issues, according to experts during two WCG webinars on acceptable methods for sites and sponsors, and best recruitment practices.

Sensors and Wearables Transform Clinical Trials but Challenges Remain, Experts Say

February 19, 2018

With a multitude of sensors, wearables and mobile devices becoming available for use in clinical trials, sponsors should conduct systematic comparisons before designing protocols, according to experts at the annual SCOPE conference, who presented the work they’ve done to demonstrate the value of using digital monitoring in their studies, as well as the obstacles they encountered.

SCOPE 2018: Advances in Big Data, Patient Centricity Could Shift Sponsor, CRO Relationships

February 19, 2018

At the annual SCOPE conference in Orlando, Fla., clinical trials experts agreed that the traditional relationship between contract research organizations (CROs) and sponsors is evolving, alongside accelerated pursuits in big data and patient centricity — with more CROs expected to share in the risks of drug development as more of a partner than a vendor.