Patient safety
Safety data collection
Safety information is collected to monitor and maintain the safety profile of all Lilly medicine. The laws governing the development, manufacturing and marketing of products (drugs or devices) require collection of adverse events.
We collect adverse event reports, which can be reported here, from all over the world and enter the information into a common electronic database to further evaluate the safety and risks of our medicines.
We also monitor the impact of our medicines, including reports of:
- Outcomes of use of a product during pregnancy (maternal and paternal exposure) and breastfeeding
- Lack of drug effect
- Off-label use
- Overdose, abuse and misuse
- Medication error
- Suspected transmission of infectious agents
- Potential adverse events associated with product complaints
Healthcare professionals play a crucial role in adverse event collection and the continuous evaluation of a product's safety profile through:
- Reporting adverse events to regulatory agencies or the manufacturer of the product
- Providing basic information related to the adverse event, such as reporter, patient, adverse event and drug
- Including any relevant information in the reports that might enable a thorough evaluation of the adverse event
- Providing additional information when contacted by the regulatory authority or the manufacturer.
Signal management
The goal of the signal management process is to identify, evaluate and communicate drug safety risks as early as possible. Signal management consists of the following components: signal detection, signal prioritisation, signal evaluation, risk evaluation and risk minimisation (including risk communication).
A safety "signal" is a report or reports of an event with an unknown causal relationship to treatment that is recognised as worthy of further exploration and continued surveillance. Safety signals are evaluated to determine if they represent a drug-related risk, and if so, to better understand the seriousness and frequency of the risk. Safety surveillance leads to the detection and analysis of potential risk factors whose confirmation helps prevent or mitigate risk in the whole or special population.
We actively search for safety signals from numerous relevant sources of safety data by using both qualitative and quantitative methodologies. Once a signal has been detected, it is evaluated to assess the possibility of a causal association between the product and the adverse event. Safety signals are assessed and evaluated by safety teams, using all relevant sources of safety data, based on clinical and medical factors such as the potential public health impact and the strength of the signal.
How is a Causal Link Evaluated?
Safety signals are assessed and evaluated, using all relevant sources of safety data, based on clinical and medical factors such as the potential public health impact and the strength of the signal. While spontaneous adverse event reports are very important for generating hypotheses and signals, there are limitations to such voluntary reporting. We may also solicit the opinion of outside expert consultants or advisory boards to help assess the evidence of possible causality.
Limitations of Spontaneous Adverse Event Reports
- Subjective and imprecise recognition of the clinical entity or the relationship with exposure to a medicinal product
- Underreporting
- Reporting biases, such as the length of time a product has been on the market, the country where the report originates, the reporting environment (e.g., media attention)
- Lack of denominator data, precluding the computation of incidence rate
Because of these limitations, our team assesses a possible causal association based on a comprehensive evaluation from all available data sources rather than spontaneous adverse events alone.
What are Potential vs. Identified Risks?
A risk may be considered "potential" or "identified (established)," depending on the strength of the evidence.
Potential Risk
An adverse event for which there is some basis for suspicion of a causal association with the medication of interest but where this association has not been confirmed is considered a potential risk.
Within the context of Lilly's signal management process, a potential risk represents a safety signal that requires additional evaluation. This may include more extensive follow-up on individual cases or more intensive monitoring activities. We also may further evaluate the potential risks by means of additional studies (clinical trials or observational studies, for example).
Identified (Established) Risk
An identified or established risk is an adverse event for which there is adequate evidence of a causal association with the medicine.
All identified risks are included in the Company's Core Safety Information (CSI). We maintain a CSI document for each marketed product, which contains the minimum relevant safety information that Lilly requires to be included in labeling in all countries where the drug is marketed.
Both identified risks and potential risks that may have prescribing implications (impacting physicians' decisions about treatment or clinical management of a patient) are included in the CSI.
What Is the Link Between the CSI and the Local Label/Prescribing Information?
When safety information is revised or added to the CSI, Lilly communicates these changes to all countries where the product is marketed. These changes are then submitted to the regulatory authority and/or implemented into the local labeling per the applicable regulations/requirements for that country.
Local requirements/regulations in some markets may require the addition of information of national or local interest or needs beyond the information provided in the CSI. There may also be instances when a regulatory authority requests substantial changes to or removal of information in the CSI. We review these requests, and when needed, negotiate the final labeling content with the applicable regulatory authorities.
Risk management activities
For each new medicine we launch, we document the important known and potential risks and how these risks will be further evaluated in a Risk Management Plan. In addition, the Risk Management Plan outlines the risk minimisation activities that will be implemented to optimise the drug's benefit-risk profile and increase patient safety. This document is regularly reviewed and updated as additional safety data becomes available.
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Regulatory reporting
Regulatory authorities worldwide, including the TGA, monitor the benefit-risk balance of marketed medicines, in accordance with each country's local or regional laws and regulations.
Based on these activities, regulatory authorities may take actions such as requesting that drug companies update the information in the product's label or conduct additional risk assessment or minimisation activities. This may include additional research to evaluate a safety risk or communications to healthcare providers/consumers to bring attention to and emphasise the new information included in the updated product label. In some instances, regulatory authorities may decide to directly communicate with the public.
By law, we are required to report safety information to regulatory authorities according to specific timelines. Following approval, we continue to inform health authorities on the safety of our products through the submission of expedited individual case safety reports, periodic aggregate safety reports, clinical study reports, and other relevant communication on safety issues in a timely manner consistent with applicable regulations.
We are also required to promptly communicate with regulatory authorities when we become aware of any new safety information that might influence the evaluation of a product's benefits and risks.
Communicating to healthcare providers and patients
We communicate safety findings for our medicines to regulators, patients and/or healthcare providers—whether favourable or unfavourable to our product. We attempt to provide information appropriate to each audience in an accurate, objective and balanced manner, in order for physicians and patients to make more informed decisions about Lilly medicines.
When safety surveillance activities lead to a change in the benefit-risk balance of a product, this change is communicated to healthcare providers and/or patients through the following:
- Updates to the Investigator Brochure and/or informed consent document for clinical trials
- Revision of labelling (package insert) for marketed products
- Providing safety information to physicians via Dear Healthcare Professional Letters; to patients via Consumer Medicines Information and Instructions for Use; or to the public via press releases
It is important for Lilly, regulators, healthcare providers and patients to work together to ensure that everyone participates in reporting any adverse event that might be attributed to a medicine.