MONITORING IN CLINICAL TRIALS

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MONITORING IN CLINICAL TRIALS

• Valérie Salzman, Pharm D

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Monitoring

• Definition
• The act of overseeing the progress of a clinical
  trial, and of ensuring that it is conducted,
  recorded, and reported in accordance with the
  protocol, SOPs, GCP, and the applicable
  regulatory requirement(s)
• Key player Monitor (or CRA)
• plays a critical role in initiating and
  conducting trials. Acting as the main line of
  communication between the sponsor and the
  investigator
• ICH guideline for GCP 1996

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Monitoring

• History
• the profession appeared late 70s early 80s in
  USA, became distinctive in Europe late 80s
• with concomitant laws
• Qualifications
• no specific level of education is required but
  a monitor should be appropriately trained and
  should have the scientific and/or clinical
  knowledge needed to monitor the trial adequately
  
• ICH guideline for GCP 1996

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Monitoring

• Extent of responsibilities depends on country,
  company, qualifications
• recruiting investigators, initiating and
  conducting the trial, writing/reviewing trial
  documents, training investigators, preparing
  authorization file,...
• Professional skills
• compulsive need for accuracy
• patience, tact, negotiating talent
• addiction for traveling

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Before the trial Feasibility

• Verify that the investigator is able to safely
  and properly conduct the trial
• qualified by education, training, experience
• having sufficient time, qualified and informed
  staff, adequate facilities and equipment
• motivation
• able to demonstrate a potential for recruiting
• absence of competition

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Before the trial study set-up

• Check that regulatory requirements are fulfilled
  (ethical committee approval, authorisation from
  Regulatory Authority)
• Control availability of trial material
• Train the investigators team about the trial
  (technical protocol, case report form,
  therapeutic units)

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On site monitoring the main questions

• Does the patient exist ?
• Has the patient been informed, did he accept to
  take part in the trial ?
• Does the investigator follow the approved
  protocol ?
• Does he report adverse events adequately?
• How are investigational products used ?
• The monitor is the only person able to answer...

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Preparation of the monitoring visit

• Appointment with
• trial related personnel investigator, nurse,
  pharmacist,...
• Mail or fax
• for confirmation
• describing material to prepare medical records,
  returned units, case report forms,
• problems to resolve

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Course of the visit

• Preliminary interview
• how are the patients?
• any serious adverse event ?
• any lost to follow-up ?
• Verifications
• source data verification (versus medical records
  medical history, clinical events, treatments)
• protocol adherence
• medical review and clinical coherence
• Post interview
• clarifications
• resolution of problems
• Data sheet recovery

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Beside this ideal situation...

• To deal with
• availability of people (patient emergency,
  crowded consulting room,)
• installations (place, table, plug,)
• site management (lost or unavailable documents,
  equipment failure)
• To identify and order priorities
• ethics or protocol violations, SAE

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After the monitoring visit

• Visit report including
• main points of the visit
• list of problems to resolve
• Mail
• to list the main problems identified during the
  visit and solutions adopted
• to thank

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Monitoring

• It is the first input for the reliability and
  coherence of the clinical data
• It assures the quality of the data reported in
  terms of efficacy and safety
• It contributes to the quality of the trial and
  prepares adequately the registration file

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What is an e-CRF ?

• Web-based application used
• by investigators to enter patient data
• by all authorised persons to retrieve and review
  individual data
• to post and resolve all queries
• trial portal various web traditional
  functions
• download documents,
• workflows, mails, alerts, reports, charts .

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Main benefits

• Real time access to data
• Interactivity between all actors of the trial
• Concomitant queries with data entry
• Improve adherence to the protocol
• On line access to study documents
• Allow e-mail alert for any event
• Decrease the duration between the last visit of
  the last patient and trial results

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How does it work ?

• Use of a Web portal
• Security
• Secured, authenticated and encrypted connections
• Automatic Log off, detection of intrusions
• 24/7 back up and disaster recovery plan
• Use of electronic signature User
  Identification Password Date
• Site
• Assessment diagnosis of computers lines,
  provisioning (lap-top, ADSL)
• e-support training, 24/7 help desk