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Pharmacovigilance in clinical trials

Victoria Nambasa
Manager Pharmacovigilance
National Drug Authority

• Importance of Pharmacovigilance
• Key definitions
• Reporting timelines
• Gaps and opportunities

• The science and activities relating to the detection. 2004) . assessment and prevention of adverse reactions to drugs. What is Pharmacovigilance? • Pharmacovigilance is concerned with the detection. understanding and prevention of adverse effects or any other drug related problem (WHO. assessment.

• The goals of adverse event monitoring – Protect subjects in clinical study – Protect future patients by determining risk benefit and risk factors once a product is marketed – Protect future patients by allowing new drugs to be made available . Why Pharmacovigilance in CT? • Majority of safety information considered prior to market authorization is derived from controlled clinical trial.

 An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding). or disease temporally associated with the use of a medicinal (investigational) product.” 5 . whether or not related to the medicinal (investigational) product. Key Definitions • Adverse Event ICH E6: “An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. symptom.” 21CFR part312.32 (a) “Adverse event means any untoward medical occurrence associated with the use of a drug in humans. whether or not considered drug related.

Definition-2 • An Unexpected Reaction: An adverse reaction. or expected from the characteristics of the drug. the nature or severity of which is not consistent with description on the reference safety information(IB for CT). market authorization. .

Definition -3 • based on patient/event outcome or action criteria usually associated with events that pose a threat to a patient's life or functioning.  results in persistent or significant disability/incapacity  is a congenital anomaly/birth defect. serves as a guide for defining regulatory reporting obligations  results in death.  is a medically important event or reaction .  is life-threatening  requires inpatient hospitalisation or results in  prolongation of existing hospitalisation.

safety.  should inform a subject when medical care is needed for intercurrent illness(es) of which the investigator becomes aware. and well-being of all trial subjects. related to the trial. Special attention should be paid to trials that may include vulnerable subjects • The Investigator  Ensure that adequate medical care is provided to a subject for any adverse events. including clinically significant laboratory values. Who is monitoring? • The IRB/IEC safeguard the rights. .

. Investigator-2 • All SAEs should be reported immediately to the sponsor. Investigator's Brochure) identifies as not needing immediate reporting • Comply with the applicable regulatory requirement (s) related to the reporting of unexpected serious adverse drug reactions to the regulatory authority(ies) and the IRB/ IEC. .g. – except for those SAEs that the protocol or other document (e.

Who is monitoring-3 • The Sponsor: – Monitoring of the site – Expedited reporting of individual reports (CIOMS or MedWatch etc) Narrative Unblinding – Ongoing Safety Evaluation .

the sponsor. Sponsor –site monitoring – Verify that: “Adverse events. concomitant medications and intercurrent illnesses are reported in accordance with the protocol on the CRFs.” – Determining whether all adverse events (AEs) are appropriately reported within the time periods required by GCP. the IRB/IEC. and the applicable regulatory requirement(s). . the protocol.

2005)  Planning Prior to study. For trails involving special groups. Establish medical monitoring plan During the study After completion  Procedures(roles and responsibilities. details of outcome measure is important and how it will be obtained. frameworks for decision making. implementation of risk mitigation measures? .g lab. Ensure protocol includes detailed safety outcome measures if specific safety issues are anticipated e. ECG. Systematic systems for monitoring safety(CIOMS Working Group VI.

Systematic systems for monitoring safety-2 People Project management Data access Milestones .

The purpose of expedited reporting is to make regulators.Reporting requirements for adverse events in clinical trials Expedited reporting. important information on serious reactions. investigators. • The purpose is to ensure the safety of trial subjects and allow rapid reaction should the conduct of the trial need to change . and other appropriate people aware of new.

but the basic premise and definitions are generally applicable • Largely based upon the definitions in ICH-E2A • Data also form the part of the body of evidence used for benefit:risk assessment at Marketing Authorisation Application (MAA). Reporting requirements-2 Most countries have a legislative basis for the expedited reporting of potential Adverse Events/ Drug Reactions (ADRs) • Local requirements can differ substantially. .

depending on the product and any specific safety concerns or other AEs of special interest could also be reported . What is subject to expedited reporting • Individual case safety reports (ICSRs): – Generally require the presence of four valid elements as a minimum – Identifiable patient (usually provided through Clinical Trial IDs) – Identifiable reporter (Investigator) – A suspect drug or drugs – An event Usually only SUSARs. at the request of HAs . However.

etc – In EU also includes events related to the protocol design and procedure.g.. important preclinical findings. . What is subject to expedited reporting-2 Other safety information – Safety information from other observations that could change the benefit: risk evaluation for the product or affect the safety or trial subjects. e. increased frequency of expected events.

Increased frequency or severity. IRBs.. PI reports within 48 hours to the sponsor Sponsor to the RA within 7 days • Other information to be reported expeditiously: – Any change to benefit risk: e.important pre-clinical findings . investigators: also to be notified Uganda. Timelines • SUSAR – Fatal and life threatening: 7 days – All other SUSARS: 15 days – Follow up information: 15 days after receipt – Ethic committees.g.

• Lack of comprehensive Pharmacovigilance plans in protocols. . Gaps existing • Failure to report SAE • Failure to honor reporting timelines • Incomplete or insufficient narratives for reported SAEs.

Thank you .