02 June 23
Literature Search in Pharmacovigilance and Automation
IntroductionA key concern for all pharma companies is to keep a keen eye on publications that may mention their product and its effect on the public's health and safety. These publications can be extremely varied in volume, which would command a need for careful review of literature articles (numerous documents) received via several different sources. This review needs to take place stringently and deliberately to identify the safety concerns of a specific medicinal product. An individual screening literature articles based on their area of interest has to be very vigilant while reviewing the literature articles, even within a stipulated timeline.
In the landscape of Pharmacovigilance (PV) or drug safety, the literature search process is tightly regulated. The literature searches are conducted weekly or twice a week, depending on the number of molecules (active ingredients) for which the searches are carried out. Many pharma companies decide to conduct such searches at different frequencies due to the large volumes of publications across several languages. The European Medicines Agency (EMA) conducts such searches on behalf of multiple license holders for some active ingredients to avoid duplication, and literature articles can be downloaded from the EMA website under MLM (Medical Literature Monitoring), and for the rest, respective drug license holders should conduct literature reviews on a regular basis.
Literature screening as an integral part of safety assessmentsEven while the most recent technology-based automation can be implemented in a variety of PV activities, today we'll talk about its application to literature screening activity. The medical literature screening and monitoring process for identifying the safety and efficacy of a particular active ingredient, the literature search process, has been described briefly in Good Pharmacovigilance Practice (GVP) Module VI (Appendix 2), which clarifies that the MAHs are expected to establish consistent screening as an important part of regular drug safety operations. The purpose of the screening and assessment process is to identify valid Individual Case Safety Reports (ICSRs) related to suspected adverse reactions (ADRs) and other safety related issues.
The emphasis is also given to special situations such as drug exposure during pregnancy or lactation, off-label use, abuse, overdose, medication errors, occupational exposure with or without suspected ADRs, lack of therapeutic efficacy, therapy non-responder, treatment failure, drug ineffectiveness, spread of an infectious agent through a medicinal product or device, etc.
Literature sources represent about 3% of reports in the US FDA database. Regulators have taken action based on a review of literature reports; piperazine and the association of nitrosamines and cancer is an example.
Literature searchThe literature hits (articles received after a regular search) are screened to identify adverse drug reactions or any special situations relevant to the therapeutic area or any other safety related issues. The first and most basic activity in literature screening is to read entire article to identify reported ADRs, causal association with drug products and relevant articles related to aggregate reports such as Periodic Safety Update Reports (PSURs) and Periodic Benefit Risk Evaluation Reports (PBRERs) and others. The literature articles also serve as a source of safety concern and/or signal as well as it serves as an evidence (reference) of any safety issue.
The literature search should be conducted at least once every week in international medical and scientific journals. MAH can use well-known databases such as Medline, Embase, and PubMed, etc. that cover the majority of scientific and medical journals. MAH has to screen information about the abstracts from meetings, and draught manuscripts, which are required to be reviewed and assessed from time to time. Additionally, MAH is required to review the local literature search that has been published in regional journals.
The companies who have applied for marketing authorization have to initiate the literature search upon applying for a MAH. As soon as the application is sent for approval, literature searches for the molecule that is sent for approval should begin. This is to ensure the identification of safety signals or emerging safety issues with medicinal product.
Steps involved in the screening processAs part of the screening process, MAHs are expected to:
- Identify and understand which publication reference databases are most relevant (e.g., PubMed, Embase, etc.).
- To conduct a periodic literature search, search on these databases to receive hits for literature search.
- Maintain and always have an updated list of all the "active substances" for which the company holds marketing authorization or applied for.
- To design an appropriate literature string (using various Boolean operators) to feed into the database so that the desired output can be received in terms of hits.
- From the received hits, read each one of them to identify against the need.
- Record the results.
- Perform peer review of the initial screening.
- To identify the ICSR, potential ICSR, aggregate report relevant hit and/or any safety issue reported.
Complex and time-consuming Process: The complex and most tedious work in PV is screening search results for adverse events from medical literature. Sometimes, pharma companies may receive a huge volume of literature hits that challenge personnel to conduct searches precisely in a time-bound manner. One may receive literature searches as a mixture of duplicates as well as fresh literature hits, thereby making sorting out the previously received articles tedious.
in the volumes: As the research surrounding new indications and safety signals continues, the volume of literature continues to grow. As a result, the screening process becomes challenging. Sudden spikes in the number of references and weekly variations: due to the constant publication of articles in relation to clinical trials in conference proceedings and journals, there have been sudden spikes in the number of references and weekly variations.
Duplicate references: Search strategies for diverse drugs (sometimes combination products) are highly likely to produce duplicate references.
Regular maintenance and management of search strategies: It is a process which consumes a lot of efforts in terms of maintaining the up to date literature search against the product list string and manage database search systems regularly.
Building an ideal search strategy: A consistent approach for creating a comprehensive search strategy has not yet been defined.
Search strategy amendments and record keeping (literature strings): Identification and keeping a record of key words, terms, and phrases is time-consuming.
Increases cost of literature review: Dealing with duplicate references can add up to 30% to the cost of literature review. As well as peer review of initial screened literature also consume high efforts resulting in to increased cost to company.
AutomationAutomation has played a significant role in scientific literature screening for pharmacovigilance. Automation in literature screening helps identify ADRs and safety signals for a associated medicinal product. Automation has emerged as a promising solution to challenges, offering a faster, more accurate, and cost-effective approach to literature screening. Several automated tools and technologies are currently available for scientific literature screening in pharmacovigilance. High-end technology like Artificial Intelligence (AI) powered solutions help for active safety surveillance. Various technologies are used for literature search automation, like Natural Language Processing (NLP) and machine learning (ML) algorithms to automatically scan and classify articles based on predefined criteria. These facilitates comprehension of the relationship between drug and event during literature screening and quickly discovers ADRs from a wide range of input data.
One example of automation in scientific literature screening is the use of text mining algorithms to identify and extract relevant information from scientific articles. This can include information such as drug names, adverse events, patient characteristics, and other relevant data. The extracted information can then be analyzed and used to generate safety signals and adverse event reports.
Automation considerably assists in the reviewing process of scientific literature and effectively screens the article channel from a single interface. It radically decreases review time by automatically eliminating repeated information. Automation can help improve the literature monitoring process in the following ways:
- Reduces administrative burden using automatic import of articles, which results in reduced manual input, thus eliminating human error.
- Decrease the duplication.
- Expedites the entire process.
- Increased oversight of literature monitoring and internal KPIs.
- Inspection readiness of end-to-end processes, audit trails, and instant reports thus minimizes the risk of inspection findings
AAutomation can improve the efficiency of literature monitoring by highlighting key drug safety concepts. It can also help reduce the workload by carrying out a bulk review where multiple references can be identified as non-relevant. It assists reviewers and helps them manage risk as a priority. It expedites the reporting process and enhances quality.
As the regulatory landscape of PV keeps evolving, MAHs will need to adapt and overcome process challenges from time to time and should be highly updated all the time to be compliant. Enabling effective PV requires a strong literature screening process. Choose a solution that can diligently address the current and anticipated need for literature screening.
Advantages of automation:Acquire speed: Automating the search and review processes would allow a major reduction in manual effort and time spent on manual monitoring.
Induce flexibility: Adaptable workflows can be customized based on need of specific safety information.
Cost-effective approach: Delivering efficient and effective results of literature search by reducing the time and resources required which turn the table for companies as cost effective model by eliminating the manual efforts.
Provide security: This would enable your team to have a record of the user who has checked for adverse events. This would also help to monitor all document activity, from identification to reporting time.
Improved accuracy and consistency of screening process.
Implementing an automated literature search process is a crucial step to helping pharma companies grow. This would help them to establish efficiency, accuracy, security, and speed for your reporting timelines.
Implementing effective workflows for literature monitoring begins with establishing a strong knowledge of compliance requirements and tight reporting deadlines. One should be able to identify key word requirements, terminologies, and search criteria to optimize search results and ensure accuracy. Additionally, integrating literature monitoring into your existing PV program will centralize the process into one holistic solution, facilitating consistency and accuracy in your reporting.
ConclusionRegardless of the volume of literature and labor-intensive process, literature monitoring is an essential responsibility for MAHs because it serves as the primary source for the safety evaluation of pharmaceutical products. Automation is the answer and the new range of possibilities for businesses. The protean approach in terms of technology adaptation that we follow at Fidelity Health Services offers automated literature screening services as per the needs of the company as their preferred PV partner.