Ensuring Quality
CTTI Webinar Highlights the Importance & Benefits of Quality by Design
A recent CTTI webinar brought together stakeholders from across the clinical trials enterprise for an overview of Quality by Design (QbD), existing CTTI resources, and how QbD is being implemented in the real world.
QbD is defined as the absence of “errors that matter”—or, those errors that could jeopardize the ability to 1) protect patients during the trial, and 2) obtain reliable results and meaningful information from the trial. CTTI started working on QbD in 2011, with a focus on addressing ineffective clinical trial monitoring. It was determined that monitoring should be viewed as only one component of an overall quality framework. From there, CTTI went on to develop a broad set of evidence-based recommendations and resources to help drive adoption of QbD.
During the webinar, CTTI walked stakeholders through its QbD Toolkit, which is split into three sections that allow users to:
- Learn about QbD;
- Introduce QbD to their organizations via workshops and printable resources; and
- Adopt QbD within their organizations.
CTTI also reviewed other available resources, such as the QbD Principles document, a key tool for QbD implementation.
Jean Mulinde, a senior policy advisor for the FDA, then spoke about why quality is important to clinical trials.
“QbD should be implemented at the clinical trial level and may be one component of an organization’s overarching quality management system,” Mulinde said. “Implementing QbD serves to focus the protocol and all of the operational plans necessary to implement the protocol on critical processes and data from the outset of a trial.”
Representatives from both academic and private organizations also shared their successes in QbD implementation. Hamid Moradi, a faculty member and researcher at University of California-Irvine, said that his organization hosted a CTTI-led QbD workshop to increase buy-in, which received a positive response from attendees. Moradi also discussed the QbD working group established at UC Irvine.
“This team will be a resource to investigators to help them better design and conduct their trials using QbD principles,” he said.
Currently, CTTI is working on additional QbD resources to support implementation, which it aims to announce within the next year.
CTTI Article Finds that Patients and IRBs are Amenable to Early Enrollment Strategy
A CTTI article recently published in JAMA Network Open shows that an early enrollment strategy for research on healthcare-associated pneumonia is acceptable to patients, investigators, and institutional review boards (IRBs). This strategy has the potential to speed enrollment in trials for critical new antibiotic therapies by allowing patients to be approached and consented to before being diagnosed with pneumonia.
Through its ABDD HABP/VABP Studies work, CTTI conducted qualitative interviews with 52 stakeholders—including patients at risk for pneumonia, caregivers, study investigators and coordinators, and IRB representatives—as part of formative research to assess the acceptability of the approach.
The study found that patients and caregivers had no concerns about patients being approached early and having their records monitored before they developed pneumonia. They believed that patients would be able to understand consent information before diagnosis, and shared their preferences for opt-out procedures.
IRB representatives were also supportive of an early enrollment strategy, and investigators and study coordinators indicated that the approach would not be burdensome.
New CTTI Recommendations Offer Path Forward for Decentralized Clinical Trials
CTTI released new recommendations on overcoming the legal, regulatory, and practical hurdles for planning and conducting decentralized clinical trials (DCTs) today during the DPharm: Disruptive Innovations to Advance Clinical Trials conference in Boston, Mass.
DCTs, which are run through telemedicine and mobile health care providers, offer several potential advantages, such as faster recruitment, improved retention, greater control and convenience for participants, and increased participant diversity. CTTI’s evidence-based and practical recommendations address barriers—including varying state medical licensing laws and issues with the drug supply chain of custody—that could be hindering the widespread use of DCTs.
The recommendations also offer guidance on effective DCT protocol design, investigator delegation and oversight, use of mobile health care providers, and safety monitoring. A key concept within the recommendations is that DCTs do not have to be fully decentralized, but can incorporate various procedures and activities that are common in traditional studies.
This is the third set of recommendations from CTTI’s Mobile Clinical Trials Program for FDA-regulated trials, which aims to drive the adoption of mobile technologies in an effort to improve the efficiency and quality of clinical trials. In 2017, CTTI announced recommendations for developing novel endpoints generated by mobile technologies and, in July, it unveiled new solutions for using mobile technologies for data capture in clinical trials. Recommendations addressing patient and investigator engagement regarding the use of mobile technologies in clinical trials will be released in early 2019.
CTTI Article Outlines Recommendations for Pregnancy Testing in Clinical Trials
Most clinical trials exclude pregnant women in order to minimize risk to the embryo or fetus. However, there are currently no specific guidelines for how pregnancy testing should be conducted for female trial participants of reproductive potential, nor how risks should be clearly communicated with them.
In a recent article in PLOS ONE, CTTI shares recommendations developed by experts in academia, industry, and regulatory agencies on pregnancy testing in clinical research. They include the following:
- The study protocol should clearly state the rationale for pregnancy testing and the plan for handling positive and indeterminate tests.
- Investigators should assess the balance of the advantages and burdens of the pregnancy testing plan, as well as and evaluate participant burdens regarding the likelihood of false-negative and false-positive results.
- Participant-administered home pregnancy testing should be avoided in clinical trials.
- The consent process should describe what is known about the study intervention’s potential risk to an embryo or fetus and the limitations and consequences of pregnancy testing.
CTTI also developed an online tool to estimate the potential outcomes of different pregnancy testing strategies in the proposed trial population. Together, these resources aim to help research sponsors, investigators, and institutional review boards create and review pregnancy testing plans, in an effort to conduct safer, more efficient clinical trials.
CTTI Study Shows More Efforts Are Needed to Stimulate Pediatric Antibacterial and Antifungal Drug Trials
In an article recently published in Pediatrics, CTTI researchers assess the impact of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) on pediatric antibacterial and antifungal drug trials.
The study, which evaluated pediatric trials conducted between 2007 and 2017, found that nearly two-thirds of pediatric antibacterial and antifungal drug trials were conducted under BPCA or PREA. These trials were more likely to collect pharmacokinetic data and report results than non-BPCA/PREA trials.
However, the overall number of pediatric antibacterial and antifungal drug trials was low, representing less than 1 percent of pediatric trials overall. These trials also rarely enrolled infants up to 30 days old.
The findings show that, while federal legislation is likely having an impact on pediatric antibacterial and antifungal drug trials, more efforts are needed to stimulate these trials and improve the reporting of results.
This study was conducted as part of CTTI’s ABDD Peds Trials Project, which focuses on creating efficient, evidence-based processes to accelerate the development of safe and effective pediatric antibacterial drugs.
CTTI Article Explores Facilitators and Barriers Perceived by Investigators to Successful Pediatric Antibacterial Drug Trials
Growing rates of antibiotic resistance have made the development of new antibacterial therapies an urgent public health need. This is especially true for the pediatric population, where it may take up to 10 years for clinical trials to determine safety and dosing information.
A CTTI article recently published in Contemporary Clinical Trials Communications shares findings from a survey of 73 investigators to determine facilitators and barriers to the successful conduct of much-needed pediatric antibacterial drug trials. The survey was conducted as part of CTTI’s Peds Trials work.
As outlined in the article, almost all investigators identified two factors as very important facilitators: having strong site staff and adequate funding. Other facilitating factors were related to staff expertise. Investigators rated parent concerns and obtaining consent as the most critical barriers. Other barriers included concerns about the number of blood draws and other invasive procedures, as well as having overly narrow eligibility criteria.
The survey findings suggest three areas in which to focus efforts to help facilitate ongoing pediatric antibacterial drug development:
- Improving engagement with parents of children who may be eligible to enroll in a pediatric antibacterial drug trial.
- Broadening inclusion criteria to allow more participants to enroll.
- Ensuring adequate staffing and establishing sustainable financial strategies, such as funding pediatric trial networks.
These results were used to develop CTTI’s actionable recommendations for facilitating and improving antibacterial drug trials in the pediatric population.
CTTI Charts New Pathways for Pediatric Antibacterial Drug Development
In an article recently published in the Journal of the Pediatric Infectious Disease Society (JPIDS), CTTI researchers lay out a roadmap for addressing an urgent public health issue: pediatric antibacterial drug development.
Antibacterial drugs are critically important for treating infectious diseases, but growing rates of antimicrobial resistance have made the development of new antibacterial therapies a priority for researchers and physicians. The problem is especially acute in pediatrics, because even when new drugs are developed for adults, it may be up to 10 years before the pediatric clinical trials needed to provide vital information about safety, effectiveness, and dosing in children are completed. The result of these delays is a chronic shortage of information to guide the use of new therapies in pediatric populations.
The JPIDS article, which was distilled from the results of CTTI research and expert stakeholder meetings, identifies five key areas for action aimed at overcoming barriers to conducting timely and efficient trials of new antibacterial drugs in children, including:
- Improving planning for pediatric drug development
- Streamlining processes for protocol development and trial design
- Refining approaches to seeking and obtaining informed consent
- Engaging with healthcare providers
- Emphasizing the rapid incorporation of new information into product labeling
The article reflects recommendations from CTTI’s Pediatric Antibacterial Drug Development Project, which focuses on creating efficient, evidence-based processes for developing, testing, and using antibacterial therapies in children. The “Peds Trials” Project itself is part of the larger CTTI Antibacterial Drug Development Program.
By fostering collaborative approaches that involve all stakeholders, CTTI hopes to accelerate the development of safe and effective pediatric antibacterial drugs—and to equip physicians and other healthcare professionals with the information they need to make the best possible decisions for the health of the children under their care.