Professional Documents
Culture Documents
UK Trial Managers Network EU directive workshop 18 November 2004 Clinical Trials Unit
Continuously assessing the risks and benefits of medicines, taking action if necessary to improve their safe use
adding information to the SPC, restricting use of a drug, withdrawing a drug
Pharmacovigilance regulations
Medicines for Human Use Clinical Trials Regulations 2004 - legal requirements EU directive and detailed guidance required harmonisation of laws- some flexibility Internationally accepted principles of good clinical/trial practice, data management, reporting E3, E6, E8, E2A
Pharmacovigilance responsibilities
Timely collection of data: recording and notification Appropriate assessments (data completeness, seriousness, relatedness, expectedness) Expedited and periodic reporting
Pharmacovigilance in practice
All protocols must have a PV section Risk to patients varies in the range of clinical trials. Extent of recording and notification of adverse events may vary depending on knowledge of the risks and benefits of drugs under study and aims of the trial. Responsibilities and systems to deal with recording, assessment and reporting must be clearly stated. Time frames for notification, assessment and reporting are critical As are SOPs
Important definitions
SAE: Serious Adverse event not the same as clinically severe headache can be severe but not serious CVA can be serious but not severe Adverse events and adverse reactions Expected and unexpected adverse reactions SUSAR: serious unexpected suspected adverse reaction SAR: serious adverse reaction
Data recording
Ask about occurrence of adverse events in all trial arms at each visit Information recorded in patients notes and/or CRFs (routine or AE forms) Ensure that frequency of follow up is appropriate for level of surveillance required
none in a trial of timing of antibiotic therapy 3-6 monthly in a trial of commonly used drug monthly in a trial of a new drug
Clinicians
less administrative work by trials staff may not be consistently interpreted
Collect none
Blinded trials
Try to protect blinding as much as possible, important to the integrity of the trial For placebo controlled trial, investigator can assess causality as if patient was on active treatment Trial centre can assess expectedness Only need to unblind those assessed as possible SUSARs for expedited reporting Ideally, unblinding performed by individuals not directly involved in trial e.g. a trial manager of another trial
Expedited reporting(II)
Strict time frames
Fatal or life threatening SUSAR: Not later than 7 days after sponsor had information that the case fulfilled the criteria, any follow up information within a further 8 days All other SUSARs not later than 15 days after receiving information that the case fulfilled the criteria
Reporting to investigators
SUSARs occurring in the UK and international SUSARs in an international trial need to be reported to investigators Time frame and format of reports is not specified, state in protocol gain approval from main REC Expedited, monthly, annually are up for discussion. copies of SAE form, copy of MHRA report
Summary
Overall there is a desire to reach a pragmatic solution It is do-able Define roles, responsibilities and time frames in protocol and SOPs
if agreed by ethics and MHRA in CTA application you are ok