Signal Management in Pharmacovigilance: Key Techniques and Best Practices

Signal management in pharmacovigilance is a critical aspect of ensuring drug safety and protecting public health. Its primary aim is to detect, prioritize, and evaluate potential safety signals related to medications, allowing for a better understanding of the benefits and risks associated with their use. By effectively managing these signals, healthcare professionals and regulatory authorities can implement appropriate measures to mitigate adverse drug events and optimize patient outcomes.

The process of signal management in pharmacovigilance entails ongoing monitoring of various data sources, such as spontaneous reporting databases, clinical trial data, and published literature, to identify potential safety concerns. These signals are then assessed using robust methodologies to determine their significance and validity. In recent years, technological advancements have facilitated more efficient signal detection and assessment, enabling quicker responses to emerging drug safety concerns.

Key Takeaways

• Signal management is crucial in ensuring drug safety and optimizing patient outcomes.
• The process involves continuous monitoring of various data sources to identify potential safety concerns.
• Technological advancements have significantly improved the efficiency of signal detection and assessment.

Fundamentals of Pharmacovigilance

Scope and Importance

Pharmacovigilance (PV) can be defined as the science and activities related to the detection, assessment, understanding, and prevention of adverse drug reactions or any other drug-related problems. The primary objective of pharmacovigilance is to ensure the safety and well-being of patients. As such, it plays a crucial role in monitoring the safety of pharmaceutical products, both before and after they enter the market.

In addition to promoting patient safety, the importance of pharmacovigilance lies in identifying signals that could lead to potential safety concerns. A well-functioning PV system is capable of detecting such signals early on, allowing healthcare professionals and regulatory authorities to take appropriate measures to mitigate potential risks.

Historical Context

The historical context of pharmacovigilance can be traced back to the infamous thalidomide disaster in the late 1950s and early 1960s. Thalidomide, a drug initially prescribed for pregnant women suffering from morning sickness, led to the birth of thousands of children with severe congenital abnormalities. This tragedy underlined the pressing need for systematic monitoring of drug safety and marked the beginning of modern pharmacovigilance.

Following the thalidomide incident, several regulations were put in place to strengthen drug safety monitoring and assessment processes. Over the years, the field of pharmacovigilance has evolved significantly, incorporating various methodologies and innovative technologies to improve the identification and analysis of safety signals.

Today, pharmacovigilance consists of three interlocking core disciplines:

1. Case management: This discipline is responsible for collecting, processing, and assessing individual case safety reports (ICSRs).
2. Signal management: This discipline focuses on the identification, evaluation, and monitoring of safety signals, allowing for timely identification of potential safety concerns.
3. Benefit-risk management: This discipline takes into account both the benefits and risks associated with a drug to determine its overall safety profile and inform regulatory decision-making.

In summary, the fundamentals of pharmacovigilance revolve around the continuous monitoring of drug safety, aimed at ensuring patient well-being and promoting public health. The field has grown and evolved significantly over the past few decades, marked by the emergence of innovative methodologies and advancements in technology. The historical context and the three interlocking core disciplines serve as key components of a robust PV system, all with the shared goal of protecting patients and enhancing the safe use of medicines.

Regulatory Framework

Global Regulatory Bodies

The regulatory landscape of pharmacovigilance is governed by various global regulatory bodies to ensure the safety and efficacy of medicinal products. Some key international regulators include the European Medicines Agency (EMA) and the Pharmacovigilance Risk Assessment Committee (PRAC). These organizations work together to establish guidelines for the process of signal management in pharmacovigilance.

In addition to the EMA and PRAC, other global regulatory authorities, such as the US Food and Drug Administration (FDA) and the World Health Organization (WHO), also contribute to the development of regulatory standards and guidelines for pharmacovigilance.

Regulatory Guidelines

A crucial aspect of signal management in pharmacovigilance is adhering to the regulatory guidelines issued by these various authorities. The EMA, for instance, has established a set of guidelines known as Good Pharmacovigilance Practices (GVP) that outline the best practices for signal management.

Some key guidelines and resources in pharmacovigilance include:

• EMA GVP Module IX: This guideline focuses specifically on signal management, detailing procedures such as signal detection, signal validation, signal analysis and prioritization, and signal assessment.
• EudraVigilance: The EMA operates the EudraVigilance database, a central hub for collecting, monitoring, and analyzing information on suspected adverse reactions to medical products. This system helps regulators identify potential safety signals and inform relevant regulatory actions.

When it comes to signal management in pharmacovigilance, the collaboration between various regulatory authorities is essential in developing and maintaining a standardized approach that ensures the safety of medical products and promotes public health.

Pharmacovigilance Systems

Pharmacovigilance systems are essential for the identification of safety signals and management of safety information related to the use of medicines. The primary goal of these systems is to gather and analyze data from spontaneous reporting systems and electronic health records, enabling the timely assessment and detection of potential adverse events.

Spontaneous Reporting Systems

Spontaneous Reporting Systems (SRS) are a cornerstone of pharmacovigilance. They rely on healthcare professionals, patients, and manufacturers to voluntarily report suspected adverse events. These reports are consolidated into Individual Case Safety Reports (ICSRs), which provide valuable data for detecting safety signals and monitoring the overall safety of medicines. The SRS allows for the collection of a large number of unfiltered adverse event reports, making it a useful tool in identifying previously unknown or rare issues.

There are, however, limitations to the spontaneous reporting system, such as under-reporting and missing or limited information. Nonetheless, it remains a crucial component in the ongoing evaluation of a drug’s safety profile.

Electronic Health Records

Electronic Health Records (EHRs) are an increasingly important source of data for pharmacovigilance. They offer a wealth of information, such as patient demographics, medical history, medication data, and clinical outcomes. The analysis of EHRs can help identify safety signals and trends early on, enabling proactive measures to manage potential risks.

EHRs have several advantages over spontaneous reporting systems, including:

• Availability of a large amount of patient data, allowing for more accurate assessments of prevalence and incidence rates of adverse events
• The ability to access and analyze longitudinal patient data, which can help identify temporal associations between drug exposure and adverse events
• Improved data quality, as EHRs often contain detailed and structured information on medication use and clinical outcomes

However, EHRs also have their own set of challenges, such as data privacy concerns, interoperability issues, and potential biases arising from differences in electronic record-keeping practices.

Overall, the effective use of both spontaneous reporting systems and electronic health records is essential for maintaining a comprehensive and up-to-date pharmacovigilance system. By integrating the data from these sources, safety signals can be detected, and appropriate risk management measures can be implemented, ultimately improving the safety and well-being of patients.

Signal Management Process

Signal Detection

Signal detection in pharmacovigilance is the initial step of the signal management process. It involves identifying potential safety signals of new, rare, or serious adverse events related to a medical product. Various methods can be used for signal detection, such as data mining in safety databases, using a combination of quantitative algorithms and qualitative assessment. Quantitative methods include statistical approaches, while qualitative methods involve expert review of individual case safety reports and literature sources 1.

Signal Validation

Once a potential signal is detected, it needs to be validated. Signal validation involves confirming that the detected signal is not a random occurrence or caused by confounding factors. It is essential to determine the strength and consistency of the association between the medical product and the adverse event. This process may require reviewing additional data sources, such as clinical trials, observational studies, and product usage patterns.

Signal Confirmation

Signal confirmation occurs after validation and involves further investigation to establish a causal relationship between the drug and the adverse event. It may require gathering more data from different sources, such as post-marketing surveillance, clinical trials, and epidemiological studies. Signal confirmation is crucial to determine if regulatory or risk minimization actions need to be taken for the medical product 2.

Signal Analysis

The signal analysis phase involves assessing the clinical significance and public health impact of the signal. It includes evaluating factors such as the severity of the adverse event, the frequency and duration of exposure to the medical product, and the affected population’s characteristics. It also requires comparing the medical product’s risks and benefits to determine the net effect on patient safety.

Prioritization and Assessment

The prioritization and assessment phase aims to define which signals are most critical and require immediate action. This process involves ranking signals based on their potential impact on patient safety, public health, and product usage. Factors to consider include the severity of the adverse event, the strength of the association, and the size of the affected population. Regulatory bodies and marketing authorization holders need to collaborate in prioritizing signals and determining appropriate risk management activities 3.

Risk Minimization and Communication

The final step in the signal management process involves implementing measures to minimize risks associated with the medical product and communicating the findings to healthcare professionals and the public. Risk minimization measures may include label changes, dosage adjustments, or contraindications. Communication strategies can involve sharing safety information through regulatory communications, safety alerts, and educational materials targeting healthcare providers and patients.

By following these steps in the signal management process, pharmacovigilance professionals can ensure that medical products maintain a positive benefit-risk balance and contribute to safe and effective patient care.

Data Sources and Methodologies

In the field of pharmacovigilance, ensuring the safety of drugs and evaluating their safety profile is of utmost importance. Several data sources and methodologies are employed to monitor adverse events and drug interactions. This section discusses the various data sources, such as clinical trials, post-marketing surveillance, and data-monitoring committees.

Clinical Trials

Clinical trials play a crucial role in the initial assessment of a drug’s safety profile. These studies involve controlled and monitored experiments on volunteers or patients to evaluate the efficacy and safety of new drugs. During clinical trials, investigators closely monitor participants to identify any adverse events that may arise from the drug being studied.

Data from clinical trials is further analyzed by researchers to determine the potential risks and benefits of the drug. This collected information is an essential foundation for identifying any drug safety concerns before the product is introduced into the market.

Post-Marketing Surveillance

Post-marketing surveillance encompasses the monitoring of drugs after they have been approved and are available on the market. This type of monitoring helps identify any previously unknown adverse events or drug interactions that might occur in the general population, which may not have been apparent during clinical trials due to the limited sample size and controlled conditions.

A variety of data sources are used in post-marketing surveillance, including electronic health records, spontaneous reports, prescription event monitoring, and large automated data resources. Additionally, scientific literature is thoroughly analyzed to identify any potential safety signals, which may lead to further investigation.

Data-Monitoring Committees

Data-monitoring committees, also known as independent data monitoring committees, are a group of external experts responsible for evaluating the safety, efficacy, and validity of data generated during clinical trials. These committees play a vital role in ensuring that clinical trials are conducted ethically and accordance with the study protocol.

The data-monitoring committees periodically review unblinded data from ongoing clinical trials, focusing on factors such as adverse events, efficacy, and trial conduct. If any safety concerns arise, the committee may recommend changes to the trial design or, in extreme cases, halt the study.

In conclusion, various data sources and methodologies are employed in pharmacovigilance to ensure the safety and efficacy of drugs throughout their lifecycle. The information gathered from these different sources and methodologies helps researchers identify potential adverse events and drug interactions, ultimately allowing for safer and more effective treatments to be provided to patients.

Evaluating Drug Safety

Causality Assessment

One of the key elements in pharmacovigilance signal management is the causality assessment. This process helps to establish a causal relationship between the use of a drug and the occurrence of adverse effects or illness. In this assessment, a variety of factors, such as the patient’s medical history, the timing of the drug administration, and the plausibility of the reaction are considered to determine if the drug is responsible for the observed adverse event.

A systematic approach to causality assessment includes:

• Collection of relevant patient and drug information
• Evaluation of alternative causes for the adverse event
• Analysis of the temporal relationship between drug exposure and the event

These steps provide a solid foundation to establish a link between the drug and the adverse effects, helping to identify potential safety concerns.

Benefit–Risk Balance

When assessing a drug’s safety, it is crucial to consider not only its potential risks but also its benefits. A comprehensive benefit–risk balance analysis evaluates the overall impact of the drug on patient health, encompassing both its therapeutic effects and possible adverse outcomes. This evaluation is important in determining the drug’s suitability for approval or continued marketing.

A practical approach to the benefit-risk balance involves:

• Careful consideration of the drug’s therapeutic efficacy
• Identification and quantification of known adverse effects
• Comparisons with alternative treatment options, considering both benefits and risks

An effective benefit-risk management process aims to maximize the drug’s benefits while minimizing its risks. It is important to continuously evaluate and update this balance as new information emerges throughout the drug’s lifecycle, leading to improved informed decisions about the drug’s usage.

In summary, evaluating drug safety involves assessing the causal relationship between drug use and adverse effects, as well as considering the overall benefit-risk balance. This comprehensive approach ensures that drugs provide the best possible therapeutic outcomes while minimizing potential risks for patients.

Technological Advancements

Machine Learning Applications

In recent years, machine learning has emerged as a powerful tool for enhancing pharmacovigilance systems. Machine learning algorithms can rapidly analyze large volumes of data, identifying patterns and associations that might be missed by manual assessment. One study highlights the potential of machine learning in detecting signals automatically, helping to reduce the burden on pharmacovigilance professionals and improving overall signal management efficiency.

Machine learning applications in pharmacovigilance often involve the use of data mining techniques. These techniques parse through massive datasets to uncover relationships and connections in pharmacovigilance data, leading to more accurate and timely signal detection, assessment, and response.

Disproportionality Analysis

Disproportionality analysis is a widely used statistical method for identifying potential safety signals in pharmacovigilance data. It compares the reporting frequency of specific drug-event pairs to an expected baseline, highlighting those that deviate significantly from the norm.

Advanced technologies, such as machine learning and data mining, have the potential to augment current disproportionality analysis methods, making them even more effective in spotting potential safety issues. This can lead to better risk management and improved patient safety.

Narrative Review

Narrative review is another important aspect of signal management in pharmacovigilance. It refers to the systematic and structured evaluation of both clinical and non-clinical information contained within adverse event reports, helping to identify potential safety signals and assess their credibility and significance.

Traditionally, narrative review has relied heavily on manual assessment by trained professionals. However, recent advancements in information technology and pharmacovigilance techniques have made it possible to automate many aspects of the narrative review process. With the aid of machine learning algorithms and other advanced technologies, pharmacovigilance professionals can now more quickly and accurately assess reported events, leading to a more efficient and effective signal management process.

Roles and Responsibilities

Signal management in pharmacovigilance involves various entities working together to ensure the safety of pharmaceutical products. This section will focus on the roles and responsibilities of pharmacovigilance professionals, drug manufacturers, and regulatory bodies.

Pharmacovigilance Professionals

Pharmacovigilance professionals play a crucial role in the process of signal management. Their responsibilities include:

1. Case management: They are responsible for monitoring, assessing, and reporting adverse drug reactions (ADRs) to contribute to the safety profile of a drug.
2. Signal detection: They detect signals by collectively reviewing cases and using data mining techniques to identify potential safety concerns.
3. Signal validation: They evaluate and confirm the identified signals to establish their relevance and accuracy, often involving subject-matter experts or expert panels.
4. Signal analysis and prioritization: They assess the signals in terms of frequency, seriousness, and potential impact, and prioritize them for further investigation.

These professionals work in close collaboration with drug manufacturers and regulatory bodies to ensure the effective management of safety signals throughout the product life cycle 1.

Drug Manufacturers

Drug manufacturers have a key role in monitoring and managing the safety of their products. Their main responsibilities are:

1. Establishing and maintaining a comprehensive pharmacovigilance system to ensure ongoing signal management activities.
2. Reporting ADRs and safety signals in a timely manner to regulatory authorities.
3. Implementing risk management plans (RMPs) designed to identify, characterize, and minimize potential risks associated with their products 2.
4. Regularly updating product information, such as labels and package inserts, to communicate new safety information to healthcare professionals and patients.
5. Continuous assessment of the product’s benefit-risk profile throughout its lifecycle.

Addressing and mitigating safety concerns can require collaboration with pharmacovigilance professionals, subject-matter experts, and regulatory bodies.

Regulatory Bodies

Regulatory bodies, such as the FDA and EMA, hold a significant role in signal management in pharmacovigilance. Their primary responsibilities include:

1. Reviewing and assessing safety data submitted by drug manufacturers, pharmacovigilance professionals, and other stakeholders.
2. Establishing and enforcing guidelines and requirements for pharmacovigilance processes, such as EMA’s GVP Module IX on Signal Management.
3. Taking appropriate regulatory actions, such as issuing safety warnings, updating product information, or withdrawing the product from the market, based on the assessment of safety signals.
4. Collaborating with other regulatory bodies and international organizations in sharing safety-related information and harmonizing pharmacovigilance practices.

In conclusion, signal management in pharmacovigilance is a collaborative effort involving pharmacovigilance professionals, drug manufacturers, and regulatory bodies, each with distinct roles and responsibilities. These entities work together to ensure that pharmaceutical products remain safe, and to promptly address any emerging safety concerns.

Risk Management and Post-Authorization Safety

Risk Management Plans

Risk Management Plan (RMP) is a critical component in pharmacovigilance and is designed to ensure the safe and effective use of medicinal products. RMPs are developed by pharmaceutical companies and submitted to regulatory authorities to outline the steps they plan to take in identifying, evaluating, and, if possible, minimizing the risks associated with a product. These plans are updated throughout a medicine’s lifecycle as new information becomes available. It includes information on ongoing safety monitoring as well as any post-authorization (source).

An RMP addresses several aspects, including risk identification, risk assessment, and risk minimization. This involves:

• Identifying and characterizing the safety profile of a product
• Evaluating the benefits and risks, considering the target population
• Proposing appropriate actions and measures to minimize these risks

Additionally, RMPs comprise several elements, such as routine pharmacovigilance, the post-authorization safety studies (source), and risk communication strategies.

Ongoing Monitoring

Ongoing monitoring in pharmacovigilance is vital for assessing the safety profile of medicinal products continuously, ensuring that any new safety concerns are promptly identified and addressed. One critical tool for ongoing monitoring is the use of statistical signal detection within large datasets, such as the EudraVigilance database (source). This technique employs algorithms to detect potential safety signals, which can then be investigated further.

Another method of ongoing monitoring is through Post-Authorization Safety Studies (PASS). These studies are conducted to evaluate the risks and benefits of a product following its authorization, allowing for a more comprehensive understanding of its safety profile while in use. Regulatory authorities, such as the Pharmacovigilance Risk Assessment Committee, often request these studies as part of the medicine’s risk management (source).

Effective ongoing monitoring also includes Governance and Implementation aspects. This encompasses the establishment of oversight structures and processes to ensure regulatory compliance and the execution of risk evaluation and mitigation strategies (source). Furthermore, ongoing communication between pharmaceutical companies, regulatory authorities, and healthcare providers is crucial in maintaining the safety and efficacy of medicinal products.

Overall, the interplay between Risk Management Plans and ongoing monitoring is essential in pharmacovigilance for safeguarding the health and well-being of patients. These processes allow for the early detection and management of potential safety signals, ultimately promoting the responsible use of medicinal products.

Communication and Information Dissemination

Effective signal management in pharmacovigilance heavily relies on clear communication and information dissemination to ensure that everyone involved in pharmaceutical drug development, marketing, and use stays informed about potential adverse drug effects.

Product Information

Two critical sources of information for pharmaceuticals are the Summary of Product Characteristics (SmPC) and the package leaflet. The SmPC includes essential data on the pharmaceutical, such as dosage, contraindications, warnings, and possible adverse events, to guide health professionals. The package leaflet, on the other hand, provides valuable information in an easily understandable format for patients. This document contains essential cautions, usage instructions, and potential side effects.

Regular updates to the SmPC and package leaflet are vital as pharmacovigilance signal management processes uncover new safety concerns or updates related to a drug. This proactive approach allows healthcare professionals and patients to remain informed and make appropriate decisions for treatment.

Patient and Healthcare Provider Communication

In addition to providing product information, pharmacovigilance communication channels need to establish a dialogue between patients, healthcare providers, drug manufacturers, and regulatory authorities. One method of enabling this communication is through informed consent, particularly in clinical trials. Participants need to be educated about the potential benefits and risks associated with the trial drug to make informed decisions.

Advocacy groups and patient organizations play a vital role in raising awareness about drug safety issues and ensuring that patient concerns are heard. These groups can help disseminate information that emerges from signal management processes in pharmacovigilance to a broader audience, enhancing transparency and trust in the pharmaceutical sector.

In conclusion, effective communication and information dissemination are essential components of good pharmacovigilance practices. Ensuring accurate, timely, and accessible information about drug safety allows all stakeholders to make well-informed decisions about treatment options, ultimately leading to better patient outcomes and improved public health.

Documentation and Reporting

Documentation Practices

Proper documentation is essential in the field of pharmacovigilance to ensure that any potential risks or adverse events associated with the use of pharmaceutical products are accurately and systematically recorded. The primary focus of documentation should be on suspected adverse reactions, medication errors, and drug-drug interactions. To maintain transparency and integrity, the data collected must be easily accessible, clear, and consistent across the entire organization.

One recommended documentation practice is the utilization of standardized reporting templates. These templates can help maintain consistency in the reporting process, improve data quality, and decrease the potential for errors in data interpretation. Additionally, it’s crucial to organize and store all relevant documents in a secure, comprehensive database to ensure that information is retrievable for future use. This way, the pharmacovigilance team can easily analyze and evaluate the available information regarding potential safety signals¹.

Submission of ICSRs

The Individual Case Safety Report (ICSR) is a crucial component of pharmacovigilance. It captures detailed information about suspected adverse reactions, medication errors, and drug-drug interactions associated with specific pharmaceutical products. Submission of ICSRs plays a vital role in maintaining the safety of these products and protecting public health².

When it comes to submitting ICSRs, a few crucial steps must be followed:

1. Identification of the event: The pharmacovigilance team must identify if the reported event qualifies as an adverse reaction, medication error, or drug-drug interaction.
2. Assessment and evaluation: The team should assess the available evidence and determine the severity and potential impact of the reported event.
3. Completion of the ICSR form: Based on the assessment, the team must complete a standardized ICSR form that includes all relevant data, such as patient demographics, medical history, and details about the pharmaceutical product involved³.
4. Submission to relevant authorities: The completed ICSR must be submitted to the appropriate health authorities within the specified reporting timeframe.

Regular and accurate submission of ICSRs helps health authorities monitor the safety profiles of pharmaceutical products, detect potential safety signals, and take appropriate action to mitigate risks associated with the use of these products⁴.

Footnotes

1. Signal Management in Pharmacovigilance: A review of activities and case studies ↩
2. Pharmacovigilance: An overview ↩
3. Practical applications of regulatory requirements for signal detection and communications in pharmacovigilance ↩
4. Signal detection and their assessment in pharmacovigilance ↩

Frequently Asked Questions

What are the steps involved in the signal assessment process in pharmacovigilance?

The signal assessment process in pharmacovigilance is a critical component of maintaining drug safety. The process typically involves several steps, such as signal detection, data collection, validation and evaluation of signals, and risk management. Initial signals may be identified through various sources, including spontaneous reports, literature, and databases. Once a potential safety concern arises, the information is reviewed, validated, and evaluated for potential risks and benefits. Lastly, appropriate risk management measures are implemented to ensure the safe use of drugs.

How do qualitative and quantitative methods differ in pharmacovigilance signal detection?

Qualitative methods in pharmacovigilance signal detection primarily rely on the evaluation of individual case safety reports, expert judgment, and pattern recognition. In contrast, quantitative methods use statistical analyses, including disproportionality analysis and data mining techniques, to identify potential safety signals. Both qualitative and quantitative approaches are essential in pharmacovigilance, as each has its strengths and limitations, with an emphasis on complementing each other to ensure a comprehensive assessment of drug safety signals.

What is the role of causality assessment in pharmacovigilance signal detection?

Causality assessment plays a crucial role in pharmacovigilance signal detection by determining the likelihood that a specific drug or active ingredient is responsible for an adverse event. This process helps differentiate between true safety concerns associated with a drug and those that can be attributed to other factors or coincidences. Proper causality assessment ensures that potential safety signals are not overlooked and helps prioritize resources for further evaluation and risk management.

Why is risk management essential in the context of pharmacovigilance?

Risk management is a crucial aspect of pharmacovigilance, as it serves to minimize the potential harm associated with pharmaceutical products while maximizing their therapeutic benefits. By identifying safety concerns through signal detection, pharmacovigilance professionals develop strategies and interventions to mitigate and manage these risks. Effective risk management helps protect public health, maintain patient trust, and preserve the reputation of pharmaceutical companies.

What career opportunities exist in the field of signal detection and management within pharmacovigilance?

There are various career pathways in the field of signal detection and management within pharmacovigilance, including roles such as safety data analysts, pharmacovigilance scientists, drug safety officers, and risk management specialists. These professionals work in pharmaceutical companies, contract research organizations, regulatory agencies, and international health organizations. Advanced educational degrees in pharmacy, medicine, life sciences, or related fields, coupled with relevant experience and certifications, are typically required for these positions.

How does signal intelligence enhance the practices of pharmacovigilance?

Signal intelligence, the systematic gathering and analysis of information related to drug safety signals, significantly enhances pharmacovigilance practices by facilitating the early detection of potential issues, supporting evidence-based decision making, and improving risk management strategies. It promotes proactive identification of risks, fosters collaboration between different stakeholders, and allows for quick, effective communication and intervention when necessary. This ultimately supports safer medication usage and contributes to improved public health outcomes.