Antibacterial Drug Development

Topics Included: Data Collecting and Reporting, Ensuring Quality, Innovative Trials, Patient Engagement, Regulatory Submissions + Approvals, Safety

Overview

Increasing bacterial resistance coupled with decreasing research on new antibacterial drugs is creating a crisis that could disproportionately impact our most vulnerable populations, including children and the seriously ill.  

CTTI has created approaches for streamlining antibacterial drug development that will help you design clinical trials that better assess the efficacy and safety of new antibacterial drugs and inform clinical trial planning, recruitment, enrollment, and feasibility. Use CTTI’s recommendations and resources to help combat this complex public health concern.

Projects

ABDD HABP/VABP STUDIES

Learn about CTTI’s prospective, multi-center, observational study of the risk factors for HABP/VABP.

ABDD PEDS TRIALS

Design pediatric antibacterial trials that ensure adequate enrollment, decrease the burden on sites and families, and increase engagement with healthcare providers.

ABDD STREAMLINING HABP/VABP TRIALS

Streamline protocol elements and data collection in HABP/VABP trials to increase enrollment, reduce trial complexity, and optimize operational efficiency.

ABDD UNMET NEED

Read about CTTI’s research findings on patient and physician perspectives and considerations as it relates to using antibacterial drugs developed through streamlined development processes.

Resources

Safety

Antibacterial Drug Development

Increasing bacterial resistance coupled with decreasing research on new antibacterial drugs is creating a crisis that could disproportionately impact our most vulnerable populations, including children and the seriously ill. CTTI...

Ensuring Quality | Recommendations

CTTI Recommendations: Effective and Efficient Monitoring as a Component of Quality Assurance in the Conduct of Clinical Trials

Build quality into the scientific and operational design and conduct of clinical trials. View and download CTTI's recommendations.

Ensuring Quality | Recommendations

CTTI Recommendations: Quality by Design

“Quality” in clinical trials is defined as the absence of errors that matter to decision making—that is, errors which have a meaningful impact on the safety of trial participants or...

Patient Engagement | CTTI News

CTTI Holds Meeting to Discuss Engaging Stakeholders in Trial Design

The Clinical Trials Transformation Initiative (CTTI) held a multi-stakeholder Expert Meeting on April 4 to discuss high-value approaches and situation-specific considerations for meaningful engagement of internal and external stakeholders in clinical trial...

Patient Engagement | Expert Meetings

Engaging Stakeholders in Trial Design Expert Meeting

April 4, 2023 CTTI Project: Engaging All Stakeholders in Clinical Trial Design Meeting Objectives: Review two clinical trial 'models' where stakeholder engagement was well-executed Discuss and explore opportunities, barriers, and...

Patient Engagement | CTTI News

New CTTI Project Aims to Engage All Stakeholders in Clinical Trial Design

Engaging patients and all stakeholders from the earliest stages of trial design is increasingly recognized as fundamental to planning and conducting high quality clinical trials. Yet important gaps remain, including...

Patient Engagement

Collaborative Engagement in Clinical Trial Design

Engaging the broad range of stakeholders from the earliest stages of trial design is increasingly recognized as fundamental to planning and conducting high quality clinical trials.

Ensuring Quality

QUALITY BY DESIGN (QbD) TOOLKIT

SHARE TO: Overview This Quality by Design Toolkit is a compilation of documents, templates, guidelines, and videos that will help you put QbD into practice within in your organization. Whether...

Ensuring Quality | CTTI News

New Case Studies Reveal Real-World Experience with Quality by Design (QbD)

Organizations are gaining experience using CTTI’s Quality by Design (QbD) recommendations to design and conduct better clinical trials. CTTI today announced four new QbD case studies, adding to its robust QbD toolkit. Three...

Regulatory Submissions + Approvals

Antibacterial Drug Development Streamlining HABP/VABP Trials

Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) occur in seriously ill, hospitalized patients, where resistance to antibiotics is rising. This makes clinical trials of antibiotics in this population not only urgent...

Formats

Stage of Trial

CTTI Recommendations: Effective and Efficient Monitoring as a Component of Quality Assurance in the Conduct of Clinical Trials

Published Date: March 24, 2025

Topics Included: Ensuring Quality

Share to:

download recommendations

CTTI encourages the use of all materials listed on this site. Click here to view our citation policy.

Primary Recommendations

Build quality into the scientific and operational design and conduct of clinical trials

Focus on what matters most

  • “Quality” is defined as the absence of errors that matter (i.e., errors that have
    a meaningful impact on patient safety or interpretation of results)
  • Determine what matters for a specific trial

Develop a quality management plan

  • Initiate plan in parallel with protocol development
  • Focus on areas of highest risk for generating errors that matter
  • Seek regulatory review of plan

Assess performance in important parameters

  • Prospectively measure error rates of important parameters
  • Tailor monitoring approach (e.g., site visits, central, statistical) to the trial
    design and key quality objectives

Improve training and procedures

  • Based on measured parameters

Report findings of quality management approach

  • Include issues found, actions taken, impact on analysis and interpretation of
    results
  • Incorporate into regulatory submissions and publications
  • Encourage inclusion in International Committee of Medical Journal Editors
    requirements

Ancillary Recommendations

Share knowledge and experience

  • Collaborate among academia, industry, and regulators to share
    methodologies and data

Encourage appropriate regulatory guidance

  • Emphasize key principles of quality trials (i.e., human subjects protection,
    reliable results, protocol adherence)
  • Encourage risk-focused oversight of trials

Promote education and awareness

  • Focus on those involved in design, implementation, analysis,
    interpretation, regulation, inspection, and publication of clinical trials
  • Include users of results (e.g., health care providers, doctors, patients)

Seek international adoption and harmonization

  • Facilitate global adoption of proposed changes

References

Landray MJ, Grandinetti C, Kramer JM, et al. Clinical Trials: Rethinking How We
Ensure Quality. Drug Information Journal November 2012; 46:657-660.

Morrison BW, Cochran CJ, White JG, et al. Monitoring the quality of conduct of
clinical trials: a survey of current practices. Clinical Trials June 2011; 8(3):342-9.

CTTI Recommendations: Quality by Design

Published Date: March 24, 2025

Topics Included: Ensuring Quality

Share to:

download recommendations

CTTI encourages the use of all materials listed on this site. Click here to view our citation policy.

Recommendations

“Quality” in clinical trials is defined as the absence of errors that matter to
decision making—that is, errors which have a meaningful impact on the safety of
trial participants or credibility of the results (and thereby the care of future
patients).

CTTI recommends that quality be built into the scientific and operational design
and conduct of clinical trials (“quality by design”) as follows:

  1. Create a culture that values and rewards critical thinking and open
    dialogue about quality, and that goes beyond sole reliance on tools and
    checklists.

    Encourage proactive dialogue about what is critical to quality for a particular
    trial or development program and, when needed, the development of
    innovative methods for ensuring quality. Discourage overreliance on
    checklists and inflexible “one size fits all” approaches that undermine creation
    of specific strategies and actions intended to effectively and efficiently support
    quality in a given study. Verify that quality and performance measures are
    aligned with incentives driving a culture that rewards critical thinking. For
    example, rewarding study teams who minimize the time to first patient
    enrolled may serve as a disincentive to devoting time to identifying and
    preventing errors that matter through trial design.
  2. Focus effort on activities that are essential to the credibility of the study
    outcomes.

    Rigorously evaluate study design to verify that planned activities and data
    collection are essential. Streamline trial design wherever feasible. Similarly,
    deploy resources to identify and prevent or control errors that matter in the
    study; in other words, determine those study activities that are essential to
    ensure the safety of trial participants and the credibility of key study results.
    Consider whether nonessential activities may be eliminated from the study to
    simplify conduct, improve trial efficiency, and target resources to most critical
    areas.
  3. Involve the broad range of stakeholders in protocol development and
    discussions around study quality.

    Engaging all stakeholders with study development is an important feature of
    quality by design. The process of building quality into the study plan may be
    informed not only by the sponsor organization but also by participation of
    those directly involved in successful completion of the study such as clinical investigators, study coordinators and other site staff, and patients. Clinical
    investigators and potential trial participants have valuable insights into the
    feasibility of enrolling patients who meet proposed eligibility criteria, whether
    scheduled study visits and procedures may be overly burdensome and lead
    to early dropouts, and the general relevance of study endpoints to the
    targeted patient population. When a study has novel features in elements
    considered critical to quality (e.g., defining patient populations, procedures, or
    endpoints), early engagement with regulators should also be considered.
  4. Prospectively identify and periodically review the critical to quality
    factors.

    The CTTI Quality by Design Principles Document and Toolkit can be used to
    identify those aspects in each study that are critical to generating reliable data
    and providing appropriate protections for research participants (“critical to
    quality factors”), and to develop strategies and actions to effectively and
    efficiently support quality in these critical areas. For example, in a
    cardiovascular major morbidity outcomes trial, strategies to ensure that the
    survival status of all trial participants is captured would be critical, but source
    verifying participants’ temperature readings obtained as a part of vital sign
    assessments at routine study visits is unlikely to be considered critical to the
    successful outcome of the study. In addition, because new or unanticipated
    issues may arise once the study has begun, it is important to periodically
    review critical to quality factors to determine whether adjustments to risk
    control mechanisms are needed.

 

CTTI Holds Meeting to Discuss Engaging Stakeholders in Trial Design

The Clinical Trials Transformation Initiative (CTTI) held a multi-stakeholder Expert Meeting on April 4 to discuss high-value approaches and situation-specific considerations for meaningful engagement of internal and external stakeholders in clinical trial design and implementation. Engaging all stakeholders during the earliest stages of study development is an important feature of quality by design (QbD). Aligned with CTTI’s QbD approach, the Engaging Stakeholders in Trial Design Project team is developing an engagement roadmap and recommendations to enable clinical trial designers to meaningfully and effectively engage all stakeholders across the trial design process. The project team is also collating resources surrounding the engagement of stakeholders to increase the efficiency of trial design to benefit patients faster. 

Experts from academia, clinical research organizations, patient advocacy groups, regulatory agencies, and the pharmaceutical industry discussed the challenges and opportunities, key strategies, and metrics for assessing holistic stakeholder engagement across the continuum of clinical trials. The following key themes were emphasized during the meeting: 

  • It is important to engage key stakeholders – including patients, site staff, and regulatory agencies – very early in the design of clinical trials. When planning study timelines, identify all internal and external stakeholders and the appropriate time and approach to solicit their input. 
  • Stakeholder engagement should be an iterative process throughout the life cycle of clinical trials. Internal and external stakeholders should be engaged, as appropriate, from the beginning of clinical trial design through the dissemination of results. 
  • Bring stakeholders and functional groups together to identify gaps between teams and brainstorm solutions to increase the quality and efficiency of trials. Effective communication and collaboration across all stakeholder groups is crucial to create a community around designing high-quality studies that meet the needs of patients and that generate reliable evidence with fewer amendments.  
  • Advanced methodologies and tools, such as artificial intelligence and machine learning, can help study designers develop innovative, high-quality trials and streamline processes. With databases of real-world and clinical trial data, artificial intelligence and machine learning can be used to inform the design of trials, explore potential treatments for patient subgroups, assess feasibility of enrollment, and identify sites. 
  • A collection of resources for designing clinical trials, including recommendations on how and when to meaningfully engage all stakeholders, is needed to help study designers plan innovative clinical trials more efficiently and in alignment with regulatory guidance. 

Engaging Stakeholders in Trial Design Expert Meeting

Meeting Objectives:

  • Review two clinical trial ‘models’ where stakeholder engagement was well-executed 
  • Discuss and explore opportunities, barriers, and best practices for study designers to engage all stakeholders in trial design 
  • Identify situation-specific considerations for ensuring engagement is appropriately equitable, effective, and feasible 

Meeting Materials:

  • Welcome Remarks and Opening Comments 
    • Introduction to the Clinical Trials Transformation Initiative (CTTI) 
    • Engaging Stakeholders in Trial Design Project Overview 
    • Meeting Objectives 
  • Session 1: Models for Success 
    • Review of two well-executed trials 
    • Key milestones and interactions that supported success 
    • Discussion: What does a well-engaged trial look like? 
      • Methods and milestones 
      • Roadblocks to engagement 
  • Session 2: Challenges and Opportunities 
    • Panel discussion: opportunities, barriers, and best practices for engaging all stakeholders in trial design 
      • Building the value proposition of engaging stakeholders in trial design 
      • Timing of stakeholder engagement 
      • Operationalizing stakeholder feedback 
      • Simplifying the process  
      • Measuring the impact 
  • Session 3: Break Out Sessions 
    • Timing of stakeholder engagement 
    • Simplifying the stakeholder engagement process 
    • Measuring the impact of stakeholder engagement in the design of clinical trials 

The views and opinions expressed in these presentations are those of the individual presenter and should not be attributed to the Clinical Trials Transformation Initiative, or any organization with which the presenter is employed or affiliated. 

New CTTI Project Aims to Engage All Stakeholders in Clinical Trial Design

Engaging patients and all stakeholders from the earliest stages of trial design is increasingly recognized as fundamental to planning and conducting high quality clinical trials. Yet important gaps remain, including a lack of comprehensive resources for engaging all stakeholders and a unifying framework, especially one tied to regulatory guidance.

To address these gaps, CTTI is starting work on a new project that will result in an engagement roadmap, multi-stakeholder recommendations, and supporting resources for effectively and efficiently engaging all stakeholders in the design of clinical trials. This project aims to identify:

  • Specific opportunities and high-value approaches/methods/tools for study designers to engage with internal and external stakeholders across the clinical trial design and planning process.
  • Situation-specific considerations for ensuring engagement is appropriately equitable, effective, and feasible.

In carrying out this work, CTTI will conduct iterative design and evidence gathering activities, including a landscape scan, user-testing and formal research aimed at reaching consensus across stakeholders on suggested engagement, and one or more multi-stakeholder expert meetings to review and synthesize findings.

By taking a multifaceted approach, CTTI will create resources that will enable clinical trial designers to collectively and coherently use various existing methods to engage all stakeholders across the trial design process – leading to more efficient, higher quality research in alignment with CTTI’s vision for clinical trials by 2030.

Collaborative Engagement in Clinical Trial Design

Topics Included: Ensuring Quality, Patient Engagement

Engaging all collaborative partners from the earliest stages of trial design is increasingly recognized as fundamental to planning and conducting high quality clinical trials. CTTI’s project, Collaborative Engagement in Clinical Trial Design, will create an engagement roadmap with supporting resources that will enable clinical trial designers to efficiently and effectively engage all partners across the trial design process, in alignment with CTTI’s vision for clinical trials by 2030.

Resources

Safety

Antibacterial Drug Development

Increasing bacterial resistance coupled with decreasing research on new antibacterial drugs is creating a crisis that could disproportionately impact our most vulnerable populations, including children and the seriously ill. CTTI...

Ensuring Quality | Recommendations

CTTI Recommendations: Effective and Efficient Monitoring as a Component of Quality Assurance in the Conduct of Clinical Trials

Build quality into the scientific and operational design and conduct of clinical trials. View and download CTTI's recommendations.

Ensuring Quality | Recommendations

CTTI Recommendations: Quality by Design

“Quality” in clinical trials is defined as the absence of errors that matter to decision making—that is, errors which have a meaningful impact on the safety of trial participants or...

Patient Engagement | CTTI News

CTTI Holds Meeting to Discuss Engaging Stakeholders in Trial Design

The Clinical Trials Transformation Initiative (CTTI) held a multi-stakeholder Expert Meeting on April 4 to discuss high-value approaches and situation-specific considerations for meaningful engagement of internal and external stakeholders in clinical trial...

Patient Engagement | Expert Meetings

Engaging Stakeholders in Trial Design Expert Meeting

April 4, 2023 CTTI Project: Engaging All Stakeholders in Clinical Trial Design Meeting Objectives: Review two clinical trial 'models' where stakeholder engagement was well-executed Discuss and explore opportunities, barriers, and...

Patient Engagement | CTTI News

New CTTI Project Aims to Engage All Stakeholders in Clinical Trial Design

Engaging patients and all stakeholders from the earliest stages of trial design is increasingly recognized as fundamental to planning and conducting high quality clinical trials. Yet important gaps remain, including...

Patient Engagement

Collaborative Engagement in Clinical Trial Design

Engaging the broad range of stakeholders from the earliest stages of trial design is increasingly recognized as fundamental to planning and conducting high quality clinical trials.

Ensuring Quality

QUALITY BY DESIGN (QbD) TOOLKIT

SHARE TO: Overview This Quality by Design Toolkit is a compilation of documents, templates, guidelines, and videos that will help you put QbD into practice within in your organization. Whether...

Ensuring Quality | CTTI News

New Case Studies Reveal Real-World Experience with Quality by Design (QbD)

Organizations are gaining experience using CTTI’s Quality by Design (QbD) recommendations to design and conduct better clinical trials. CTTI today announced four new QbD case studies, adding to its robust QbD toolkit. Three...

Regulatory Submissions + Approvals

Antibacterial Drug Development Streamlining HABP/VABP Trials

Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) occur in seriously ill, hospitalized patients, where resistance to antibiotics is rising. This makes clinical trials of antibiotics in this population not only urgent...

Formats

Stage of Trial

QUALITY BY DESIGN (QbD) TOOLKIT

Overview

This Quality by Design Toolkit is a compilation of documents, templates, guidelines, and videos that will help you put QbD into practice within in your organization. Whether you are first learning about QbD (Learn About QbD), want to disseminate these concepts within your organization (Teach Others About QbD), or are ready to implement QbD into your clinical trial (Adopt QbD), this Toolkit has resources for you. Refer back to the Toolkit often and find new resources to support you in translating QbD from principles to practice.

 

New Case Studies Reveal Real-World Experience with Quality by Design (QbD)

Organizations are gaining experience using CTTI’s Quality by Design (QbD) recommendations to design and conduct better clinical trials. CTTI today announced four new QbD case studies, adding to its robust QbD toolkit. Three of the case studies are also now featured in CTTI’s recently-announced Building Better Clinical Trials: A Case Study Exchange resource.

The case studies provide an in-depth look at real-word implementation of QbD principles by:

  • Alexion, a biopharmaceutical company focused on developing medicines for rare diseases, applied QbD principles early in study design to build a streamlined, simple protocol for a global Phase III trial on a tight timeline.
  • An investigator at the Duke Clinical Research Institute applied QbD principles to thoughtfully and strategically design a 1,000 patient, multicenter trial that can be largely executed remotely.
  • The Medicines Company (now part of Novartis), a small pharma company that applied QbD principles with two collaborators to plan a 5-year trial that is already seeing faster-than-expected recruitment.
  • University of Oxford’s Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) followed a QbD approach in planning and conducting a streamlined, mail-based trial that enrolled over 15,000 participants.

QbD is not a checklist, rather it is a common sense approach in which stakeholders consider: (1) what aspects of a trial are critical to generating reliable data and providing appropriate protection of research participants (“critical to quality” factors); and, (2) what strategies and actions will effectively and efficiently support quality in these critical areas.

These new case studies not only describe the critical-to-quality factors for each trial, and how they were addressed, but also provide tangible strategies and examples for how other organizations can implement such an approach.

This news comes on the heels of CTTI announcing:

  • New resources for the adoption of a QbD approach – including a QbD Maturity Model, Metrics Framework, Implementation Guide, and Documentation Tool – at the end of 2020; and
  • Building Better Clinical Trials: A Case Study Exchange, announced in March 2021; three of the case studies announced today will be included in this resource.

Want to be featured on Building Better Clinical Trials: A Case Study Exchange?

If you are part of an organization that has used any of CTTI’s recommendations or tools and would like to be featured on the site, we may be able to include your story.

By sharing your experience, you can showcase your organization’s success while providing helpful information that will benefit other organizations and facilitate collaboration and knowledge sharing across the research community.

Please reach out to Karisa Merrill to learn more.

Antibacterial Drug Development Streamlining HABP/VABP Trials

Topics Included: Data Collecting and Reporting, Ensuring Quality, Innovative Trials, Regulatory Submissions + Approvals

Program: Antibacterial Drug Development

Related Projects: Antibacterial Drug Development HABP/VABP Studies, Antibacterial Drug Development Peds Trials, Antibacterial Drug Development Unmet Need

Overview

Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) occur in seriously ill, hospitalized patients, where resistance to antibiotics is rising. This makes clinical trials of antibiotics in this population not only urgent but also especially challenging.

Use CTTI’s recommendations to streamline protocol elements and data collection in HABP/VABP trials to increase enrollment, reduce trial complexity, and optimize operational efficiency and, ultimately, help combat the current public health crisis in antibiotic development. 

Resources

Safety

Antibacterial Drug Development

Increasing bacterial resistance coupled with decreasing research on new antibacterial drugs is creating a crisis that could disproportionately impact our most vulnerable populations, including children and the seriously ill. CTTI...

Ensuring Quality | Recommendations

CTTI Recommendations: Effective and Efficient Monitoring as a Component of Quality Assurance in the Conduct of Clinical Trials

Build quality into the scientific and operational design and conduct of clinical trials. View and download CTTI's recommendations.

Ensuring Quality | Recommendations

CTTI Recommendations: Quality by Design

“Quality” in clinical trials is defined as the absence of errors that matter to decision making—that is, errors which have a meaningful impact on the safety of trial participants or...

Patient Engagement | CTTI News

CTTI Holds Meeting to Discuss Engaging Stakeholders in Trial Design

The Clinical Trials Transformation Initiative (CTTI) held a multi-stakeholder Expert Meeting on April 4 to discuss high-value approaches and situation-specific considerations for meaningful engagement of internal and external stakeholders in clinical trial...

Patient Engagement | Expert Meetings

Engaging Stakeholders in Trial Design Expert Meeting

April 4, 2023 CTTI Project: Engaging All Stakeholders in Clinical Trial Design Meeting Objectives: Review two clinical trial 'models' where stakeholder engagement was well-executed Discuss and explore opportunities, barriers, and...

Patient Engagement | CTTI News

New CTTI Project Aims to Engage All Stakeholders in Clinical Trial Design

Engaging patients and all stakeholders from the earliest stages of trial design is increasingly recognized as fundamental to planning and conducting high quality clinical trials. Yet important gaps remain, including...

Patient Engagement

Collaborative Engagement in Clinical Trial Design

Engaging the broad range of stakeholders from the earliest stages of trial design is increasingly recognized as fundamental to planning and conducting high quality clinical trials.

Ensuring Quality

QUALITY BY DESIGN (QbD) TOOLKIT

SHARE TO: Overview This Quality by Design Toolkit is a compilation of documents, templates, guidelines, and videos that will help you put QbD into practice within in your organization. Whether...

Ensuring Quality | CTTI News

New Case Studies Reveal Real-World Experience with Quality by Design (QbD)

Organizations are gaining experience using CTTI’s Quality by Design (QbD) recommendations to design and conduct better clinical trials. CTTI today announced four new QbD case studies, adding to its robust QbD toolkit. Three...

Regulatory Submissions + Approvals

Antibacterial Drug Development Streamlining HABP/VABP Trials

Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) occur in seriously ill, hospitalized patients, where resistance to antibiotics is rising. This makes clinical trials of antibiotics in this population not only urgent...

Formats

Stage of Trial