Duke Clinical Research Institute - PowerPoint by DL8RMcQ

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									What Makes a Top 10 Site: An
     ARO Perspective
 Michele Rund RN BS, Senior Lead CRA
   Cardiovascular Phase 1 & 2, DCRI
Objectives



     Describe the characteristics of an effective
      research site
     Understand the regulatory environment
      within and outside your site
     Identify 3 methods to improve data quality at
      your site
Huge topic- needs ongoing learning



  Will focus on characteristics of effective sites
   in three areas
     Protocol, Patient and Coordinator
     Regulatory Environment
     Data Quality
Characteristics of Effective Sites- #1



      An excellent Clinical Research Coordinator
         Educated
         Organized
         Institutionally “savvy”
         Attention to detail
Coordinator Responsibilities


            Day to day trial management
            Trial Implementation
            Primary Contact
            Regulatory Submissions
            Recruitment
               Screening & Enrollment
Coordinator Responsibilities


          Protocol required testing
          Drug/Device accountability
          Data Collection and Submission
          Audit Preparation
Clinical Research Coordinators

   “In almost every field of endeavor,
  there is a small group of individuals
  who are responsible for the success
   of the mission, but get little credit.
   And in our field we all know who I
         am talking about- study
              coordinators.”
       Dr. Bill Berger, CenterWatch, 1997
Education- Regulatory Practice



     Drug/Device Research is heavily regulated
     Education should be ongoing from a variety
      of sources
     Internet Resources
Education- Benefits for CRC and Sponsors


     Prompt and accurate submission of
      regulatory documents can contribute to
      early start of enrollment
     Good relationships with IRB’s can help
      expedite the approval process and ensure
      safeguards for patients
     Institutional knowledge can shorten contract
      execution time
Education- Benefits for CRC




      Learn the process
      Take advantage of opportunities
      Help to improve medical care for patients
       globally
Regulatory Resources
       Internet
          www.ctnbestpractices.com
          FDA www.fda.gov
          OHRP (Office for Human Research
           Protection) www.hhs.gov/ohrp
          NIH Online http://www.nih.gov
           http://ohrp.osophs.dhhs.gov/
          Applied Clinical Trials
             www.actmagazine.com
Characteristic # 2- Protocols that Fit


     Thorough & Thoughtful review of protocols
      is a valuable process for both site & sponsor
     PI’s and sites can provide expert scientific
      and medical input which contributes to
      successful clinical trials
     Type and Phase of Trial
     Assess Protocols from 4 perspectives
Protocols That Fit- Types of Trials

     Phase 1                       Phase 2
        Small, intense                Size varies

        80- 100 participants          Volunteer patients

        Normal, healthy               Early assessment of
         volunteers                     effectiveness
        Study safety profile,         Safety, PK & PD in
         PK & PD                        target population
        Labwork intense!              Labwork intense

        Very fast data                Fast data turnaround
         turnaround
Protocols That Fit- Types of Trials


     Phase 3
        Large patient population
        Duration is longer
        Efficacy and safety
        Need for fast data clean up particularly at the
         end of the study
Protocol Assessment


            Study Design
            Patient Population
            Protocol Requirements
            Scientific Benefits
            Financial Considerations
Protocol Assessment- Scientific
Considerations
     Does the study design support its
      objectives?
     Are the objectives and expected outcomes
      clearly expressed
     Are the data to be collected appropriate for
      determining safety & efficacy of the product
     Are the inclusion/exclusion criteria realistic
      for the disease under investigation?
     Is the protocol compatible with your site’s
      philosophy or goals?
Protocol Assessment- Regulatory
Considerations
     Protocols are required to contain information in 21
      CFR 312.23 (a) (6) (iii) aka the 1572
     Criteria for patient selection (incl/exclu), # of
      patients, design of study, type of control group,
      methods to minimize bias
     For drug studies method of determining dose,
      maximum dose and duration of subject exposure
     Description of observations and measurements to
      fulfill study objectives, clinical procedures,
      laboratory tests, other measure to minimize risk and
      monitor the effects of drug
Protocol Assessment- Ethical
Considerations

      Are the risks minimized?
      Are the risks reasonable in relationship to
       the knowledge or benefits to be gained
      Is subject selection equitable?
      Are there errors or inconsistencies that
       affect the site’s ability to recruit subjects
       ethically?
Protocol Assessment- Feasibility
Considerations
         Previous history with sponsor/CRO
         Subject population
         Protocol fit
         Procedures required
         Staff Resources
         Proposed budget
Characteristic # 3- Excellent Recruitment
and Retention


      Current environment makes recruiting
       patients more difficult
      Common reasons for failure to recruit:
       delayed start-up, inadequate planning,
       insufficient effort and staff, over optimistic
       expectations
Recruitment Planning
     Assess the protocol first!
     Establish realistic estimates of the number
      of subjects and effort required
     Identify back-up/alternative populations
     Conduct feasibility study if needed
     Adequate & Trained staff
     Pre-screening
     Set goals
     Communication
Recruitment Strategies

      Understand your organization and identify
       resources
      Know your target audience
      Know your study
      Develop trial tools/team
         Streamline study and team processes
         Teach so staff is familiar with study
Recruitment Strategies



           Use advertising
              Institutional Resources
                 PR dept.
                 Internet resources
                 publications
Recruitment Strategies


            Health Education
               Community presentations
               Healthfairs

            Paid advertising
               Newspaper
               Radio/TV
               Direct Mail
Recruitment and Retention: Barriers to
Enrollment


            Subject related barriers
            Investigator related barriers
            Protocol related barriers
            “other barriers
Recruitment and Retention: Barriers to
Enrollment

      Subject Related
         Additional demands associated with study
         Dislike uncertainty in medical treatment
         Inconvenient visits/clinic scheduling
         Fear of side effects/risk of the study
         Age, cultural barriers
         Family issues
         Relationship with study staff
Recruitment and Retention: Barriers to
Enrollment- Investigator


      Role differentiation- inability to deal with
       conflicting roles
      Logistical barriers- time, resources, CRC
       turnover, overestimation of population
      Loss of motivation- money, effort, hassle
       factor
Recruitment and Retention: Barriers to
Enrollment- Protocol Related


          Disagreement with the protocol
          Entry criteria too restrictive
          Work load too heavy/complex
          Procedures too costly
Recruitment and Retention: Barriers to
Enrollment- “Other”


         Negative press
         Lengthy approval/contract process
         Poor choice of site by sponsor
         Unrealistic timelines
Retention- The Flip Side of Recruitment


            Key Issues
               Study design
               Personnel
               Facility
               Scheduling/Trial demands
               Technical Issues
               CONSENT
Retention- The Flip Side of Recruitment
      Help participants make informed decisions
       through the consent process
         Use the consent process as a time to
          educate participants
         Make sure CRC is comfortable with study
          and ICF
         Modify ICF to enhance participant
          understanding
         Make the informed consent process an
          informed decision
         Facilitate a participant to invest in the
          process by face to face communication
Retention- The Flip Side of Recruitment
     CRC’s need the time available to provide
      education, support and attention to study
      participants
     PI’s and CRC need to provide supportive
      communication to encourage compliance
     Use technology to streamline
      communication
     Encourage sponsors to communicate study
      milestones with participants
Characteristic # 4- Responsive and
Responsible PI’s

      PI responsibilities are found in 21 CFR 312
        “ensuring that an investigation is conducted
          according to the signed investigator
          statement, the investigational plan, and
          applicable regulation”
         1572 for studies under an IND
         Investigator Agreement for device studies
          (21 CFR 803, 812, 814)
Characteristic # 4- Responsive and
Responsible PI’s

      1572 Commitments
         Conduct the study in accordance with the
          protocol
         Personally conduct or supervise the
          described investigation
         Informs patients, follows requirements for
          informed consent
         Agree to report adverse experiences in
          accordance with 21 CFR 312.64
Characteristic # 4- Responsive and
Responsible PI’s
        Ensure that all associates, colleagues and
         employees assisting in the conduct of the
         study are informed about their obligations in
         meeting the above commitments
        Maintain accurate records, have them
         available for inspection
        Ensure that the IRB complies with 21 CFR
         56, agrees to report promptly, follow the
         approved protocol except to eliminate
         immediate hazards to human subjects
        Comply with all other requirements in 21
         CFR 312
Characteristic # 4- Responsive and
Responsible PI’s
  Duties that cannot be delegated
     Overall responsibility and accountability for
      the study
     1572
     Determining relatedness (causality) of an
      adverse event to an investigational product
Characteristic # 5- Really Good Data




     Clean and accurate data is the ultimate goal
     More queries= less $$$
     Data issues can seriously affect the integrity
      of a study
Characteristic # 5- Really Good Data
    CRA role in monitoring data
       Verify accuracy and authenticity of
        participants and data
       Ensure protocol/regulatory compliance
       Provide feedback to site
       Pivotal contact person
Protocol Compliance- Deviation and
Violations

       A protocol deviation is an unintended or
       unintentional failure to adhere to the pre-
       specified protocol.
      Inclusion/exclusion errors
      Lab timepoints missed/late
      Missed follow up visit due to unforeseen
       circumstances
Protocol Compliance- Protocol Violations


 A protocol violation is a noted and/or intended
   deviation that is not reported to the IRB or the
   sponsor and may adversely affect the
   participant. Reportable to IRB
    Prescribing or administering the wrong
     randomized treatment
    Incorrectly collected or documented data
Good Data- How Your CRA Can HELP

    CRA’s are trained in regulatory requirements
    CRA’s receive extensive training in the
     protocol
    Every CRA has a team of people working
     with them on the study
    A CRA’s job is to…..
CRA
    Provide assurance that the research site
     personnel, including the investigators, are
     conducting the study according to GCP
     guidelines.
    Provide assurance that all applicable
     regulatory requirements are being met by
     the investigator's site.
    Provide assurance that applicable adverse
     events are properly reported to the sponsor.
    Review of site record accuracy regarding
     drug accountability.
    Clinical trial-related activities for the sponsor
The Team Behind the CRA


     Lead CRA & Project Manager can provide
      additional support services to sites
        Regulatory assistance
        Detailed protocol information
        Identification & resolution of data problems
        Resolve Core Lab problems
        Trouble shooting payment problems
Site Metrics

  Site Metrics are important indicators of sites
    past performance in a particular type of trial
     Time from protocol sent to study drug/site
      activation
     Time from protocol sent and /or study drug
      sent to first patient enrolled
     Enrollment rate
     Query rate- time to resolution
Site Metrics




     Number of monitoring trips required versus
      number budgeted
     Time from last patient/last visit to data clean
     Core lab/lab sample adherence
Conclusion

   At its best the site/CRA/ARO relationship is
    collaborative and dynamic which can
    provide
      Meaningful & ethical medical care for
       patients
      High quality and cost effective results for
       clinical trials

								
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