Electronic health records to facilitate clinical research

Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research

Pharmacovigilance in Developing Countries: Drivers and Barriers

The Pharmacovigilance is crucial for patient safety and improving healthcare quality, particularly in developing countries where the burden of disease is high. This study examines the drivers and barriers to implementing effective pharmacovigilance systems in these countries. Increased availability and use of medicines and the globalization of the pharmaceutical industry have led to an increase in the number of adverse drug reactions and a need for harmonized pharmacovigilance regulations and reporting standards. Developing countries have made significant progress in establishing regulatory frameworks, and international organizations have provided technical assistance and resources. The use of technology, such as mobile phone applications, has made it easier to report adverse drug reactions and monitor drug safety in developing countries. However, several barriers hinder the success of pharmacovigilance systems in developing countries. These include the lack of resources, limited awareness and education, and limited access to information, making it challenging for healthcare professionals and regulatory authorities to monitor drug safety. Fragmented healthcare systems and cultural and social barriers, such as stigma associated with reporting ADRs, further compound the issue. It is essential to address these barriers to promote the successful implementation of pharmacovigilance systems in developing countries. Doing so will improve patient safety, reduce the burden of disease, and enhance healthcare quality. Future research should focus on developing strategies to overcome these barriers and promote the effective implementation of pharmacovigilance systems in developing countries

Hospital doctors' views and concerns about pharmacovigilance

Purpose: The aim of the study was to evaluate the opinions and concerns of hospital doctors about adverse drug reactions (ADRs) and pharmacovigilance. Methods: A qualitative study was undertaken using focus groups in sessions on pharmacovigilance activities conducted in thirteen clinical services of a tertiary university hospital. A total of 296 physicians participated in these sessions by giving their opinions or expressing their doubts about ADR and pharmacovigilance activities which were recorded by different observers and subsequently analysed. Results: Doctors remarked on: a) the importance, concern, frequency and specific types of ADRs that were observed in clinical practice; b) problems of clinical decision making related to the suspected ADRs; c) methods for improving detection and reporting ADRs; d) monitoring of specific ADRs or ADRs caused by specific drugs; e) and measures to prevent and minimize the risk of ADRs. Physicians expressed doubts related to: a) the basic concepts of ADRs; b) the methods of ADR identification and evaluation; c) the objectives and procedures of pharmacovigilance programmes; d) and the impact of pharmacovigilance activities. Conclusions: Hospital doctors believe that ADRs are a matter for concern in their daily clinical practice, and monitoring ADRs as well as measures for preventing the risk of ADRs are needed. Nevertheless, doctors have doubts about what an ADR is, the accuracy of diagnostic methods, the development of pharmacovigilance activities and their impact on clinical practice. Pharmacovigilance should be better explained through a continuous feedback and close relationship with hospital doctors

Information technology in pharmacovigilance: Benefits, challenges, and future directions from industry perspectives

Risk assessment during clinical product development needs to be conducted in a thorough and rigorous manner. However, it is impossible to identify all safety concerns during controlled clinical trials. Once a product is marketed, there is generally a large increase in the number of patients exposed, including those with comorbid conditions and those being treated with concomitant medications. Therefore, postmarketing safety data collection and clinical risk assessment based on observational data are critical for evaluating and characterizing a product’s risk profile and for making informed decisions on risk minimization. Information science promises to deliver effective e-clinical or e-health solutions to realize several core benefits: time savings, high quality, cost reductions, and increased efficiencies with safer and more efficacious medicines. The development and use of standard-based pharmacovigilance system with integration connection to electronic medical records, electronic health records, and clinical data management system holds promise as a tool for enabling early drug safety detections, data mining, results interpretation, assisting in safety decision making, and clinical collaborations among clinical partners or different functional groups. The availability of a publicly accessible global safety database updated on a frequent basis would further enhance detection and communication about safety issues. Due to recent high-profile drug safety problems, the pharmaceutical industry is faced with greater regulatory enforcement and increased accountability demands for the protection and welfare of patients. This changing climate requires biopharmaceutical companies to take a more proactive approach in dealing with drug safety and pharmacovigilance

Implementing a centralised pharmacovigilance service in a non-commercial setting in the United Kingdom

The implementation of a pharmacovigilance service compliant with the legal and regulatory responsibilities of clinical trial sponsors presents particular challenges for sponsors in a non-commercial setting. In this paper we examine these challenges in detail. We identify and discuss the key steps in the development of a pharmacovigilance service within a public health service and university setting in the United Kingdom. We describe how we have established a central Pharmacovigilance Office with dedicated staff and resources within our organisation. This office is supported by an electronic pharmacovigilance reporting infrastructure developed to facilitate the receipt and processing of safety information, the onward reporting in compliance with legislation and the provision of sponsor institution oversight of clinical trial participant safety. An education and training programme has also been set up to ensure that all relevant staff in the organisation are fully aware of the pharmacovigilance service and are appropriately trained in its use. We discuss possible alternatives to this approach and why we consider our solution to be the most appropriate to ensure that a non-commercial sponsor organisation and investigators are operating in a fully compliant way

Medication Risk Management: A Subjective Review of Present Scenario

Historically, the FDA has interpreted the requirement that a drug must be “safe” to mean that the benefits of a drug outweigh its risks. The determination was made on a “categorical” basis, where the totality of risks was weighted against the totality of benefits when considered for the purposes outlined in the drug product’s labeling. If a drug did not meet this criterion, it was not approved or its label was rewritten to narrow the conditions for use. This logic was endemic in the FDA for most of the 20th century. On average, two to four drugs over each 5-year period were withdrawn from the marketplace after post-marketing surveillance data uncovered new risks. Similarly, on occasion, the FDA would require some special “tool” or intervention to improve a product’s safety profile. Harm associated with medication remains the second most common type of incident in hospitals, as reported by the Clinical Excellence Commission. Health services actively review medication safety. The vast majority of medication errors result in no injury.  A minor injury may result, for example, in a patient needing an increased level of monitoring.  Even if incidents result in minor injury, managers and staff still take any errors very seriously, reviewing the actions around the incident and making improvements as a result. FDA’s new concepts for risk management amount to a “cultural shift” in the logic of drug approval and the FDA’s role. The key events that led to this change can be traced to a series of reports that highlighted the need for improved medical safety. In 1999, the IOM released a report entitled, “To Err is Human.” This report reviewed the nature and cause of medication errors, estimating that up to 98,000 people died each year due to these errors. In their assessment the IOM included both adverse drug reactions and human errors in drug administration. The report captured the attention of news reporters and the government. Headlines proclaimed alarm at the larger number of fatalities caused by medical errors. Consequently, there was a government-wide initiative started to develop methods and institute procedures to reduce medical errors. Statements made by FDA officials regarding some of these withdrawals suggested that the FDA no longer believed that passive oversight and re-labeling drugs with new warnings was sufficient. Furthermore, the FDA no longer believed that it was sufficient to identify safe conditions of use in the label and that healthcare professionals and patients had to comply with advocated directions of use for the drug to remain on the market

Using the Literature to Identify Confounders

Prior work in causal modeling has focused primarily on learning graph structures and parameters to model data generating processes from observational or experimental data, while the focus of the literature-based discovery paradigm was to identify novel therapeutic hypotheses in publicly available knowledge. The critical contribution of this dissertation is to refashion the literature-based discovery paradigm as a means to populate causal models with relevant covariates to abet causal inference. In particular, this dissertation describes a generalizable framework for mapping from causal propositions in the literature to subgraphs populated by instantiated variables that reflect observational data. The observational data are those derived from electronic health records. The purpose of causal inference is to detect adverse drug event signals. The Principle of the Common Cause is exploited as a heuristic for a defeasible practical logic. The fundamental intuition is that improbable co-occurrences can be “explained away” with reference to a common cause, or confounder. Semantic constraints in literature-based discovery can be leveraged to identify such covariates. Further, the asymmetric semantic constraints of causal propositions map directly to the topology of causal graphs as directed edges. The hypothesis is that causal models conditioned on sets of such covariates will improve upon the performance of purely statistical techniques for detecting adverse drug event signals. By improving upon previous work in purely EHR-based pharmacovigilance, these results establish the utility of this scalable approach to automated causal inference

Evaluating the Safety Profile of Non-Active Implantable Medical Devices Compared with Medicines

Recent safety issues involving non-active implantable medical devices (NAIMDs) have highlighted the need for better pre-market and post-market evaluation. Some stakeholders have argued that certain features of medicine safety evaluation should also be applied to medical devices. Our objectives were to compare the current processes and methodologies for the assessment of NAIMD safety profiles with those for medicines, identify potential gaps, and make recommendations for the adoption of new methodologies for the ongoing benefit–risk monitoring of these devices throughout their entire life cycle. A literature review served to examine the current tools for the safety evaluation of NAIMDs and those for medicines. We searched MEDLINE using these two categories. We supplemented this search with Google searches using the same key terms used in the MEDLINE search. Using a comparative approach, we summarized the new product design, development cycle (preclinical and clinical phases), and post-market phases for NAIMDs and drugs. We also evaluated and compared the respective processes to integrate and assess safety data during the life cycle of the products, including signal detection, signal management, and subsequent potential regulatory actions. The search identified a gap in NAIMD safety signal generation: no global program exists that collects and analyzes adverse events and product quality issues. Data sources in real-world settings, such as electronic health records, need to be effectively identified and explored as additional sources of safety information, particularly in some areas such as the EU and USA where there are plans to implement the unique device identifier (UDI). The UDI and other initiatives will enable more robust follow-up and assessment of long-term patient outcomes. The safety evaluation system for NAIMDs differs in many ways from those for drugs, but both systems face analogous challenges with respect to monitoring real-world usage. Certain features of the drug safety evaluation process could, if adopted and adapted for NAIMDs, lead to better and more systematic evaluations of the latter