Ethics

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.

CTTI Among the Spotlighted Consortia Focused on Drug Development Challenges

Posted on by Lorri Bingham

The latest issue of Nature Reviews Drug Discovery highlights several consortia that have resulted from the FDA’s Critical Path Initiative, launched nearly a decade ago. CTTI is among these initiatives and was featured in the article, The Clinical Trials Transformation Initiative: innovation through collaboration.

This publication explains the crisis in the clinical trials enterprise and CTTI’s unique role in developing actionable solutions. Several CTTI project are highlighted, including Quality by Design, Central IRB, and Investigational New Drug Safety Reporting. For each of these projects, the authors identify the issue at hand and go on to explain CTTI’s efforts to implement recommendations, noting both the difficulties and imperative of creating cultural and organizational change. The authors also comment on the ability of CTTI’s evidence-based work to inform policy and practices in the interest of public health.

“By creating an environment of trust, we enable the stakeholders — representing all sectors of the enterprise — to think about practical solutions to the identified problems and to develop strategies to effect change.”
– Pamela Tenaerts, Leanne Madre, Patrick Archdeacon, and Robert Califf

Ethicist Dr. Felix Gyi Remembered for his Commitment to Human Subjects Protection

Posted on by Lorri Bingham

We are saddened by the unexpected passing of Dr. Felix A. Khin-Maung-Gyi, executive chairman and founder of Chesapeake Research Review LLC.

Dr. Gyi’s contributions to CTTI and the greater clinical trials community will not be forgotten. As an ethicist specializing in clinical research, he was both well respected and passionate about human subjects protection. In addition to establishing Chesapeake IRB, he also served as a member of CTTI’s Steering Committee and was instrumental in spearheading CTTI’s Central IRB Project as a team lead.

The CTTI staff send our condolences to Dr. Gyi’s family, friends and colleagues.

“Felix Gyi will be remembered at CTTI for his enthusiastic efforts to catalyze our first IRB Project. We will all miss his passion and contribution to the clinical trials community.”

-Pamela Tenaerts, CTTI’s Executive Director

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.

 

CTTI Presents at the SCT 35th Annual Meeting

Posted on by Lorri Bingham

On May 18-21, 2014, the Society for Clinical Trials (SCT) will be hosting the SCT 35th Annual Meeting in Philadelphia, PA. This meeting is intended for a wide range of professionals representing academia, the pharmaceutical and device industries, government agencies and medical groups and centers. We are pleased to announce that CTTI will be present at this conference to share the ideas and lessons generated from several CTTI projects:

  • Team Lead for CTTI’s Central IRB Advancement Project, Cynthia L. Hahn will be presenting in Invited Session 8: Using a Centralized IRB Review Process in the Conduct of Multi-center Trials.
  • CTTI’s Director of Stakeholder Engagement, Bray Patrick-Lake will be presenting in Invited Session 14: NINDS INSPIRE Workshop: Patient Engagement & Patient-Centeredness – A Holistic Approach to Clinical Trial Design & Implementation. Key points for this session are related to CTTI’s Patient Groups & Clinical Trials Project.
  • Bray Patrick-Lake will also be part of a team leading a pre-conference workshop on May 18, 2014. This half-day workshop (Workshop P7) will take place from 1:00 PM – 5:00 PM and will cover the Best Practices and Innovations in Patient and Community Engagement in Clinical Trials. Advance registration and payment are required for pre-meeting workshops. CLICK HERE to complete the registration form for the SCT 35th Annual Meeting.

We look forward to connecting with the presenters and attendees of the SCT 35th Annual Meeting. Together, we can facilitate change in the clinical trials enterprise.

INNOVATION THROUGH COLLABORATION

If you are attending this conference and active on Twitter, here’s what you need to know:

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.