Safety

CTTI Releases New Tools to Help Organizations Implement Central IRBs in Multi-Center Clinical Trials

Posted on by Lorri Bingham

Today the Clinical Trials Transformation Initiative (CTTI) announced new recommendations that support the use of a single institutional review board (IRB) of record for multi-center clinical trials.  Included within the recommendations are tools, such as evaluation checklists, to help sponsors, research institutions and central IRBs implement this model.

In a multi-center clinical trial, full review by each site’s IRB can lead to significant delays in study start-up and may not enhance the protection of research participants.  Since 2010 CTTI has been working to understand and address barriers to using a single IRB of record for multi-center clinical trials in the United States. The project was initiated because some research sites were hesitant to use a central IRB, despite encouragement from the U.S. Food and Drug Administration (FDA) and the U.S. Office of Human Research Protections (OHRP).

“Using a single IRB for multi-site clinical research is an important step in accelerating the translation from discoveries to health benefits. The Clinical and Translational Science Awards (CTSA) program is working toward using a single IRB for multi-site studies. The CTTI Central IRB recommendations will be very helpful in advancing towards this goal,” said Petra Kaufmann, M.D., M.Sc., director of the Division of Clinical Innovation at the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH).

In addition to the evaluation checklists, CTTI has released a Considerations Document and an IRB authorization agreement template, to support communication and contractual relationships between institutions and a central IRB. CTTI has also hosted webinars during which individuals from sponsor and research organizations have presented their experience of adopting a central IRB model as examples that others can follow.

A complete list of recommendations can be found here.

Expert Meeting Summary Available: Multi-stakeholder Perspectives on Improving Informed Consent

Posted on by Lorri Bingham

Key stakeholders in the clinical trials enterprise acknowledge that informed consent documents are too lengthy and difficult for research participants to understand, and the informed consent process is not meeting the needs of the participants; however, there is currently little consensus around what a more effective informed consent model should look like. Actionable recommendations are needed, and CTTI is working to address this unmet need.

In March CTTI convened a multi-stakeholder group of experts and thought leaders from across the clinical trials enterprise to explore more effective informed consent processes. Specifically, the meeting attendees set out to:

  • Discuss previous and current efforts to improve informed consent documents and the informed consent process, including alternatives to the traditional paper informed consent document
  • Identify potential remedies for concisely communicating the required elements of informed consent, including how consenter training affects the informed consent process
  • Propose a more effective process, including informed consent documentation, for ensuring research participants’ understanding of critical informed consent elements
  • Suggest potential strategies and opportunities for pilot testing the informed consent process improvement recommendations

We are pleased to share the summary, as well the presentation materials from this expert meeting. These materials describe the current challenges involved with the consent process and provide an evidence-based foundation for moving forward.

Click here to view all meeting materials.

CTTI’s Tools for Improving Clinical Trial Quality & Efficiency

Posted on by Lorri Bingham

In our pursuit to enhance the implementation of CTTI’s recommendations, we’ve created a new webpage on our site that we’d like to share with you. This page features CTTI’s three most commonly used tools:

  1. The Considerations Document for a Single IRB of Record: Developed by CTTI’s Central IRB Project, this tool supports communication and contractual relationships between institutions and a central IRB to address blurred distinctions between responsibilities for ethics review and other institutional obligations. Primary users for this tool include sponsors, academic institutions, investigators, IRBs that act as a single IRB of record.
  2. The Quality by Design Principles Document: Developed by CTTI’s QbD Project, this tool helps those working in trials to promote proactive, cross-functional discussions and critical thinking at the time of trial development about what is critical to quality for a specific trial, and about the events that might impede or facilitate achieving quality. Primary users for this tool include anyone interested in designing and conducting clinical trials.
  3. The AACT Database: Developed by CTTI’s State of Clinical Trials Project, this tool makes the acquisition and analysis of the aggregate data from ClinicalTrials.gov more user-friendly. Primary users for this tool include researchers interested in analyzing data from clinical trials.

The Tools Page can be accessed on the CTTI site under Briefing Room > Tools. We hope that you find this resource valuable and share with your colleagues in the clinical trials enterprise.

NIH Encourages the Use of Central IRBs in Multi-Site Clinical Trials and CTTI’s Tools Can Assist with Implementation

Posted on by Lorri Bingham

Yesterday, the NIH issued a draft policy encouraging the use of single Institutional Review Boards (IRBs) in all NIH-funded multi-site clinical trials. The rationale behind this new policy was spelled out simply:

When regulations for protection of human subjects were first published, most clinical research was conducted at a single institution. Since then the research landscape has evolved, and many studies are carried out at multiple sites and within large networks. Multi-site studies often are able to recruit more individuals from diverse populations and generate important results in less time. However, working through IRB review at each site can add delay without increasing the ethical protections for the research participants in the study. (NIH Clinical Research Policy)

CTTI’s Central IRB Project came to similar conclusions. One of the key takeaways from this project was that sites could become more comfortable using this streamlined review model if government and commercial sponsors required the use of a single IRB as a condition for participating in a particular multi-center trial. We are pleased to see a policy in accordance with our recommendations, and that CTTI’s work was cited. We are confident that these steps will improve the efficiency of clinical trials in the US.

In their concluding remarks, the NIH points out some of the potential hurdles for adopting their guidance:

Despite enthusiasm for central IRBs, there is confusion about the optimal structure for central IRBs as well as how best to meet regulatory requirements. There are questions about the loci of responsibilities and whether the IRB or institutions will bear the blame if adverse events occur. (NIH Clinical Research Policy)

Serious adverse event reporting of is one of the items discussed in the CTTI-developed guide, known as the Considerations Document. The guide can be used by institutions and central IRBs when negotiating legal and ethical responsibilities for multi-center clinical trial.

Participate in CTTI’s Survey on Data Monitoring Committees

Posted on by Lorri Bingham

We are inviting participants to a survey from the Clinical Trials Transformation Initiative (CTTI) to gather information about the current use and conduct of Data Monitoring Committees (DMCs). We aim to gain a deeper understanding of the purpose and rationale for using DMCs, goals and responsibilities of DMCs and current conduct and communications between stakeholders using this survey and future focus groups. Your input is critical as the survey results will be considered in developing recommendations on best practices for DMC use and conduct.

WHO IS BEING ASKED TO PARTICIPATE
Current and former DMC members; and representatives of research sponsors (government, industry and academic), clinical and academic research organizations (CROs/AROs) and statistical analysis centers who directly interact with DMCs. We encourage you to forward this email to qualified colleagues.

WHAT WE ARE ASKING OF YOU
You will be asked to complete one brief, electronic survey that should take less than 15 minutes to complete. The survey is anonymous; no unique identifier will link you to your responses. In this format, please note that it is therefore necessary that you finish the survey completely before exiting out of your web browser, as the survey will not save partial responses.

PLEASE CLICK ON THIS LINK TO COMPLETE THE ANONYMOUS SURVEY.

YOUR ANSWERS WILL BE TREATED CONFIDENTIALLY
We will not be able to link your personal information such as email address and name with your answers. Your answers will be combined with those from others, and we will report answers only in aggregate.

HOW YOUR INPUT WILL BE USED
The study results will be used by CTTI to develop additional investigational activities, such as focus groups and an expert meeting. Evidence gathered from these activities will support recommendations on best practices for DMC use and conduct, to be published and used to develop toolkits for the various stakeholder groups. For more information, go to https://ctti-clinicaltrials.org/our-work/ethics-and-human-research-protection/data-monitoring-committees/.

WHO WE ARE
CTTI is a public-private partnership, established by the US Food and Drug Administration (FDA) and Duke University, whose membership includes representatives from academic institutions, clinical research organizations, institutional review boards, patient groups, pharmaceutical, biological and device companies, professional societies, US government and other stakeholders within the clinical trials enterprise. CTTI conducts projects in support of its mission to identify and promote practices that will increase the quality and efficiency of clinical trials.

WHO TO CONTACT FOR QUESTIONS
You should direct any questions or concerns regarding your survey participation to CTTI (ctti-dmcproject@duke.edu). For questions or concerns about your rights as a research subject, you can also contact the Duke Institutional Review Board (IRB) at 919-668-5111.

Thank you for your consideration,

The Clinical Trials Transformation Initiative Data Monitoring Committee Project Team Leaders:

Patrick Archdeacon
U.S. Food and Drug Administration, Center for Drug Evaluation and Research

Raymond Bain
Merck Research Laboratories

Karim Calis
U.S. Food and Drug Administration, Center for Drug Evaluation and Research

David DeMets
University of Wisconsin-Madison

Jane Perlmutter
Patient Representative

CTTI’s Announces New IND Safety Advancement Project

Posted on by Lorri Bingham

CTTI’s Executive Committee recently approved the IND Safety Advancement Project. This project is a follow-up to CTTI’s IND Safety Project, which issued recommendations in late 2013. These recommendations are intended to improve clinical trials by helping sponsors to ensure recognition of important safety issues for study drugs and biologics as early as possible during development.

Both of these projects were initiated in response to the FDA’s final rule published on September 29, 2010. This rule established new reporting requirements for serious and unexpected adverse reactions occurring in clinical trials conducted under an investigational new drug application (IND) (CFR 21.312). Although this rule, which was intended to improve the overall quality of safety, was published nearly four years ago, anecdotal reports indicate that implementation problems remain, particularly in oncology clinical trials.

While the original IND Safety Project sought to better understand current practices among sponsors for assessing and communicating the safety of an IND, the advancement project focuses on clarifying motivations and challenges to full implementation of the IND safety reporting rule. The anticipated impact of this new project is an increase in compliance with respect to assessment, communication, review, and management of serious adverse events and serious unexpected safety adverse reports.

Please visit the CTTI website for regular project updates.

CTTI Tackles 3 Issues in Clinical Trials with New Projects

Posted on by Lorri Bingham

At CTTI, we are continuously looking for practices that will increase the quality and efficiency of clinical trials. In 2014, three new topics have been added to our portfolio:

  1. Conducting Trials Using Data Registries: Demographic, disease, and outcome data collected in clinical observational registries often overlap with data gathered for clinical trials. Integrating clinical trials within observational data registries may offer opportunities to avoid duplicative data collection and increase efficiency while decreasing clinical trial costs. Objectives for this project include identifying upfront costs and operational adjustments required to utilize a data registry for a clinical trial, as well as recommending best practices for conducting randomized registry trials.
  2. Data Monitoring Committees (DMCs): As the use of DMCs has increased and evolved over the past 40 years, critical issues have emerged. A few of these issues include differences in DMC roles and responsibilities, which contributes to confusion and unclear expectations, as well as a lack of a clear plan for preparing the next generation of DMC members. Objectives for this project include understanding the current landscape of DMC use and conduct, clarifying the purpose of and rationale for using a DMC, and describing effective communication practices between independent DMCs and other trial stakeholders.
  3. Investigator Turnover: While an enormous amount of time and resources are spent initiating new investigators into the clinical trial process, there continues to be a high turnover rate for investigators. As many as 40% of investigators annually choose not to participate in another FDA-regulated trial. This high rate of attrition impacts site and overall trial performance. Objectives for this project include obtaining a more thorough understanding of the factors that influence investigators’ decisions to leave the clinical research practice, as well as defining the impact of investigator turnover on industry and society.

 

New Publication Addresses Rising Antibiotic Resistance and Clinical Trial Design

Posted on by Lorri Bingham

On June 23, 2014, an article titled Hierarchical nested trial design (HNTD) for demonstrating treatment efficacy of new antibacterial drugs in patient populations with emerging bacterial resistance was published online in Statistics in Medicine. This article describes a novel clinical trial model to determine efficacy of antibacterial drugs in trial populations with emerging antibiotic-resistant bacterial infections.

Authors Mohammad Hugue and colleagues cite the CTTI-hosted Statistical Issues Think Tank where they and other experts were able to exchange ideas that in part lead to the development of the model.

For more information on this meeting, including the list of attendees, agenda, presentations, and background summary, CLICK HERE.

New Publication Points to Need for Aggregate Safety Data Reports in IND Research

Posted on by Lorri Bingham

This week, the journal Therapeutic Innovation & Regulatory Science published a peer-reviewed article, titled Industry Practices for Expedited Reporting to Investigators Conducting Research Under an IND, assessing the range of industry practices for safety monitoring and expedited reporting to U.S.-based investigators of IND research in late 2009.

In a small sample of survey respondents, most of whom represented relatively large pharmaceutical and biological companies, the authors found that these organizations maintain “robust structures, procedures, and staffing to manage large volumes of safety data and to meet specific requirements of expedited reporting to multiple regional and local regulatory authorities. However, their focus at the time of the survey was clearly on notification and assessment of individual case reports of SAEs. In contrast, respondents reported less emphasis on, and greater variation in, aggregate analysis, interpretation, and reporting of safety data. This pattern is consistent across multiple areas of safety data management, including procedures, clinical monitoring, use of external resources, and safety reporting.”

The authors concluded:

“These data suggest that investigators would likely benefit if industry sponsors decreased reporting of individual cases that are not readily interpretable and instead reported meaningful safety information from aggregate analyses.”

This publication resulted from CTTI’s SAE Reporting Project. For more information about this project, CLICK HERE.