Medical and scientific literature is a valuable source of safety information that helps in monitoring benefit-risk profiles and emerging safety issues of medicinal products. Literature screening is conducted to ascertain abstracts and articles that provide crucial information on serious and non-serious Individual Case Safety Reports (ICSR) reports and risk-benefit assessment of a drug.
The scientific literature is screened to identify individual adverse drug reactions or any special situations relevant to the therapeutic area. The literature is targeted to identify records such as ICSRs of adverse reactions, and aggregate reports-PSURs, PBRER and DSUR. The literature is also a source for the eventual follow-up and identification of a safety signal which is a new adverse event that has not occurred or seen before for a particular drug.
Marketing authorization holders (MAHs) are required to monitor and maintain awareness of possible suspected Adverse Drug Reactions (ADRs). The other important safety information to be monitored by MAHs are the class effects, off-label use, misuse and potential drug interactions at least once every week through a systemic literature review of widely used reference databases such as Medline, Embase etc. Reports of suspected adverse reactions from medical literature, including relevant published abstracts from meetings and draft manuscripts are anticipated to be reviewed and assessed from time to time.
Marketing authorization applicants are expected to conduct literature search before obtaining the marketing authorization. As the application is sent for approval, literature searches should begin to ensure the identification of any safety signals or emerging safety issues that could impact the benefit-risk ratio of the medicinal product.
Literature screening – An integral part of safety assessments
The medical literature has been designated in line with the provisions set out in GVP Module VI that clarifies that regulators expect consistent screening to be an integral part of day-to-day drug safety operations and is based on the use of literature databases such as Embase.
The purpose of the screening and assessment process is to identify valid ICSRs related to
- Suspected adverse reactions originating from spontaneous reports in humans
- Special situations such as the use of a medicinal product during pregnancy or lactation or in the elderly population, off-label use, abuse, overdose, medication errors, and occupational exposure with suspected adverse reactions.
- Lack of therapeutic efficacy: suspected adverse reactions related to quality defects in medicinal products
- To understand spread of an infectious agent through a medicinal product.
Outline of steps involved in the Screening Process
An important aspect of pharmacovigilance, literature screening is more than just a drug safety regulatory requirement. It provides insights into safety issues like drug interactions to identify patient safety risks and preparation of critical reports that may have to be sent to regulatory bodies. This is incredibly time-consuming and labour-intensive work, with the risk of inefficiencies such as duplications. It requires judicious processing of records as it puts market authorization holders (MAH) at risk of non-compliance and regulatory fines. As part of the screening process, MAHs are expected to:
- Identify and understand which publication reference databases are most relevant to each medicinal product (E.g. PubMed, Embase etc.).
- Systematically monitor these databases for publications worldwide not frequently but at least once a week.
- Intrinsically monitor all the “active substances” for which the organisations hold Marketing Authorisations.
- Monitor articles published locally in each territory where the product is marketed
- An initial review of the records should be performed based on title, keywords, citations and the available abstract.
- Records, which could qualify for ICSR reporting, are moved to an inclusion group and which do not qualify for ICSR reporting, are archived in an exclusion group with the exclusion criteria recorded.
- These records are further screened for any duplications as several reference databases are used to ensure wider journal coverage.
- The results obtained are routed to the appropriate departments within the company to comprehend and comply with the time deadlines that apply to Individual Case Safety Reports Literature Screening.
- Analyse and elaborate about any “new and significant safety findings” in the medicinal product’s PSUR (Periodic safety update report).
- Immediately notify regulators of new safety information obtained from screening.
Challenges associated with Literature Screening
Growing regulatory scrutiny from regulatory bodies resulting in increased compliance requirements is placing additional pressure on sponsors. Additionally, the screening process itself is complex leading to multiple challenges which the marketing authorization applicants (MAAs) must navigate carefully.
- Growing volumes of literature – As the research surrounding new indications and safety signals, the volume of literature continues to grow. As a result, the screening process becomes challenging for the MAAs.
- Unexpected spikes in the number of references and weekly variations – Due to constant publications of articles in relation to clinical trials in conference proceedings and journals.
- Duplicate references – Search strategies for diverse drugs and data migration are highly likely to produce duplicate references.
- Regular maintenance and management of search strategy – It is a tedious process to maintain 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 -record keeping – Identification and keeping a record of key words, terms and phrases is time-consuming.
- Output formats vary widely making it hard to reuse data downstream.
- Increases cost of Literature review – Dealing with duplicate references can add up to 30% the cost of literature review.
Role of automation in improving literature monitoring process
Automation in literature screening helps identify both new and important ICSRs of Adverse Reactions and periodic safety update reports (PSUR) of a relevant medicinal product. The use of Natural Language Processing (NLP) aids in understanding the relationship between sentences during literature screening and quickly identifies ADEs from an extensive range of sources such as Embase and PubMed.
Automation considerably assists in the reviewing process of scientific literature and effectively screens the article channel from a single browser interface. It radically decreases review time by automatically eliminating repeated information. Automation can help improvise 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
- Decreases duplication of articles
- A clear day zero which ensures consistency, reduces risk and saves time
- (International Standards Organization (ISO) Individual Case Safety Report (ICSR) standard) E2B R3 XML output for more efficient integration with downstream applications
- Expedites identification/ submission of serious ICSRs to case processing by using AI / Machine Learning (ML)
- Demonstrates, mechanizes and tracks quality control
- Increases oversight of outsourcing partners and internal KPIs
- Inspection readiness of end-to-end process, audit trail, instant reports thus minimizing the risk of inspection findings
- All software used in PV is part of the quality management system –validation is necessary
Machine learning (ML) 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. ML model assists reviewers and helps them manage risk as a priority. It expedites the reporting process and augments quality.
As the regulatory landscape of pharmacovigilance keeps evolving, MAHs will require to adapt and overcome process challenges from time to time. Enabling effective PV requires a strong literature screening process. Biopharma organizations will require expert assistance and advanced solutions that can guide them with a compliant and efficient approach. Choose a solution that can diligently address the current and anticipated regulatory guidelines for literature screening.
Techsol’s Compier Literature Screening Solution Overview
Identifying adverse events from medical literature is one of the key and most complex tasks in pharmacovigilance (PV). The huge volume of data available makes it difficult to conduct searches precisely, and only five percent of references retrieved are relevant. Literature screening has an extra layer of complexity, added by the issue of duplication of articles. On the other hand, regulatory authorities demand high levels of quality management, which is required to operate and meet the demanding standards.
Literature screening is one of the highly focused areas of PV at Techsol. We help companies identify all kinds of elements needed to screen literature articles using NLP (natural language processing). Our advanced NLP technology helps understand relationships in sentences in literature from a screening point of view. With this technology, we can help companies reduce 60% of manual effort and provide increased compliance which will directly influence the cross-savings for the companies.
Our service is structured to deliver quality outcomes for your pharmacovigilance system and is acutely focused on the recurrent review and quality check of literature references. Leveraging our global Compier Literature screening service delivers costs benefits through our scale of operation, and allows you to focus on other areas of your core business.