The REporting of A Disproportionality Analysis for DrUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Explanation and Elaboration.

In pharmacovigilance, disproportionality analyses based on individual case safety reports are widely used to detect safety signals. Unfortunately, publishing disproportionality analyses lacks specific guidelines, often leading to incomplete and ambiguous reporting, and carries the risk of incorrect conclusions when data are not placed in the correct context. The REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance (READUS-PV) statement was developed to address this issue by promoting transparent and comprehensive reporting of disproportionality studies. While the statement paper explains in greater detail the procedure followed to develop these guidelines, with this explanation paper we present the 14 items retained for READUS-PV guidelines, together with an in-depth explanation of their rationale and bullet points to illustrate their practical implementation. Our primary objective is to foster the adoption of the READUS-PV guidelines among authors, editors, peer reviewers, and readers of disproportionality analyses. Enhancing transparency, completeness, and accuracy of reporting, as well as proper interpretation of their results, READUS-PV guidelines will ultimately facilitate evidence-based decision making in pharmacovigilance.

The Reporting of a Disproportionality Analysis for Drug Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Development and Statement.

BACKGROUND AND AIM: Disproportionality analyses using reports of suspected adverse drug reactions are the most commonly used quantitative methods for detecting safety signals in pharmacovigilance. However, their methods and results are generally poorly reported in published articles and existing guidelines do not capture the specific features of disproportionality analyses. We here describe the development of a guideline (REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance [READUS-PV]) for reporting the results of disproportionality analyses in articles and abstracts. METHODS: We established a group of 34 international experts from universities, the pharmaceutical industry, and regulatory agencies, with expertise in pharmacovigilance, disproportionality analyses, and assessment of safety signals. We followed a three-step process to develop the checklist: (1) an open-text survey to generate a first list of items; (2) an online Delphi method to select and rephrase the most important items; (3) a final online consensus meeting. RESULTS: Among the panel members, 33 experts responded to round 1 and 30 to round 2 of the Delphi and 25 participated to the consensus meeting. Overall, 60 recommendations for the main body of the manuscript and 13 recommendations for the abstracts were retained by participants after the Delphi method. After merging of some items together and the online consensus meeting, the READUS-PV guidelines comprise a checklist of 32 recommendations, in 14 items, for the reporting of disproportionality analyses in the main body text and four items, comprising 12 recommendations, for abstracts. CONCLUSIONS: The READUS-PV guidelines will support authors, editors, peer-reviewers, and users of disproportionality analyses using individual case safety report databases. Adopting these guidelines will lead to more transparent, comprehensive, and accurate reporting and interpretation of disproportionality analyses, facilitating the integration with other sources of evidence.

Are drug safety measures harmonized? A real-world evidence from three regulatory authorities.

Background: Risk minimization measures (RMMs) are interventions intended to mitigate or prevent the occurrence of adverse reactions associated with medications. Having consistent measures across regulatory bodies (i.e., the Saudi Food and Drug Authority (SFDA), the United States Food and Drug Administration (US FDA), and the European Medicines Agency (EMA)) benefits medication use and safety and ultimately the patient. Objectives: This study aimed to investigate whether there is variability in these published RMMs between the three regulatory bodies. Methods: A specific data collection form was created to extract information from the SFDA's RMM list, US FDA's Risk Evaluation and Mitigation Strategy (REMS) list, and EMA's Risk Management Plan (RMP) list, as of February 2022 all RMMs that were available on the websites were reviewed. Medications with the same trade name were matched across regulators, and unmatched medications were checked for approval status. For medication groups such as NSAIDs in the SFDA's RMM list, they were matched by searching for the groups individually in the regulatory websites. All risks and types of minimizing measures were compared. Results: A total of 317 medications were retrieved from the SFDA's RMM list. The majority of medication classes were immunosuppressants (n = 60), antihypertensive (n = 33), and oncology medication (n = 29). There were only 62 medications with REMS from the US FDA website, a total of 14 medications were approved by the SFDA, and only nine medications were matched with the SFDA's RMM list. Also, there were 828 medications with RMP from the EMA website, a total of 334 has RMM, 128 are approved by the SFDA, and 71 matched with the SFDA's RMM list. Furthermore, seven medications were matched between SFDA, US FDA and EMA. After content review, four medications had similar risks and measures across the regulators and three medications had different risks and measures across the regulators. For the medication groups, a total of 36 groups were in the SFDA's list, 18 groups were matched with the US FDA, and 14 were matched with the EMA. Conclusions: Our study showed substantial differences among the regulatory authorities regarding RMMs. Harmony in published risk measures can have a significant impact on medication safety.

Clinical Characterization of Patients Diagnosed with Prostate Cancer and Undergoing Conservative Management: A PIONEER Analysis Based on Big Data.

BACKGROUND: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. OBJECTIVE: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. DESIGN, SETTING, AND PARTICIPANTS: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. RESULTS AND LIMITATIONS: The most common comorbidities were hypertension (35-73%), obesity (9.2-54%), and type 2 diabetes (11-28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12-25%) and emergency department visits (10-14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. CONCLUSIONS: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. PATIENT SUMMARY: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.

Evaluating the impact of alternative phenotype definitions on incidence rates across a global data network.

Objective: Developing accurate phenotype definitions is critical in obtaining reliable and reproducible background rates in safety research. This study aims to illustrate the differences in background incidence rates by comparing definitions for a given outcome. Materials and Methods: We used 16 data sources to systematically generate and evaluate outcomes for 13 adverse events and their overall background rates. We examined the effect of different modifications (inpatient setting, standardization of code set, and code set changes) to the computable phenotype on background incidence rates. Results: Rate ratios (RRs) of the incidence rates from each computable phenotype definition varied across outcomes, with inpatient restriction showing the highest variation from 1 to 11.93. Standardization of code set RRs ranges from 1 to 1.64, and code set changes range from 1 to 2.52. Discussion: The modification that has the highest impact is requiring inpatient place of service, leading to at least a 2-fold higher incidence rate in the base definition. Standardization showed almost no change when using source code variations. The strength of the effect in the inpatient restriction is highly dependent on the outcome. Changing definitions from broad to narrow showed the most variability by age/gender/database across phenotypes and less than a 2-fold increase in rate compared to the base definition. Conclusion: Characterization of outcomes across a network of databases yields insights into sensitivity and specificity trade-offs when definitions are altered. Outcomes should be thoroughly evaluated prior to use for background rates for their plausibility for use across a global network.

Interferon-λ3 rs12979860 can regulate inflammatory cytokines production in pulmonary fibrosis.

Pulmonary fibrosis (PF) is the last phase of interstitial lung diseases (ILDs), which are a collection of pulmonary illnesses marked by parenchymal remodeling and scarring. Treatment can only halt the functional decline of the lung, raising the necessity of identifying the basic processes implicated in lung fibrogenesis. The Interferon lambda-3 (IFNL3) gene variant, rs12979860, was determined to be related to an elevated risk of fibrosis in different organs, but the mechanism through which it mediates fibrogenesis is not clear. In the current research, we aim to figure out some of the mechanistic pathways by which IFN-λ3 mediates ILDs. 100 healthy controls and 74 ILD patients were genotyped for IFNL3 rs12979860. Then the mRNA expression of IFNL3 and some other proinflammatory mediators was examined according to genotype in the peripheral blood mononuclear cells (PBMCs) of ILDs patients. The IFNL3 rs12979860 genotype distribution of healthy individuals and ILDs patients was shown to be in Hardy-Weinberg equilibrium (HWE) with a minor allele frequency (MAF) of 0.293 and 0.326, respectively. Furthermore, the CC genotype was demonstrated to be linked to enhanced IFNL3 expression. Also, the CC genotype was linked to an increase in the mRNA expression of TLR4 (P = 0.03) and the inflammatory cytokines IL-1ß and TNF-α (P = 0.01 and 0.04, respectively) and had no effect on the NF-kB level (P = 0.3). From these results, we can deduce that IFN-λ3 may mediate tissue fibrosis via increasing the expression of IFN-λ3 itself and other proinflammatory mediators. This stimulates a self-sustaining loop mechanism which includes a reciprocal production of IFN-λ3, TLR4, IL-1ß, and TNF-α leading to persistent inflammation and fibrosis.

The association between drug pricing and drug shortage in Saudi Arabia: a retrospective database analysis.

BACKGROUND: Previous studies have suggested that drug pricing could contribute to drug shortages; however, there is limited quantitative assessment of this potential causal association. This retrospective database analysis aimed to investigate the association between drug prices and drug shortage incidents in Saudi Arabia. METHODS: This was a retrospective database analysis study. Drugs with shortage notifications sent to the Saudi Food and Drug Authority (SFDA) between January 2017 and December 2020 were included. Each drug's foreign-to-Saudi price ratio (FTSPR) was calculated by dividing the mean international price by the Saudi price. Drugs were categorized into three groups based on their FTSPR: Group 1 (FTSPR > 1), Group 2 (FTSPR = 1), and Group 3 (FTSPR < 1). The primary outcome was the ratio of mean counts (mCR) between the three groups, with Group 3 serving as the control group. The analysis was adjusted for the measured confounders using a negative binomial regression model. RESULTS: A total of 900 drugs were included in the study, with 348 in Group 1, 345 in Group 2, and 209 in Group 3. The mean count in Group 1 was higher compared to Group 3 (mCR: 1.88; 95% confidence interval [CI] 1.24 to 2.83), while the mean counts between Group 2 and Group 3 were comparable (mCR: 1.39; 95% CI 0.92 to 2.09). CONCLUSIONS: Our findings indicate an association between drug shortage incidents and higher prices of drugs outside Saudi Arabia. Further studies are needed to explore this causal relationship in different contexts.

The use and safety risk of repurposed drugs for COVID-19 patients: lessons learned utilizing the Food and Drug Administration's Adverse Event Reporting System.

Objectives: This study was designed to assess the disproportionality analyses of adverse drug reactions (ADRs) related to hydroxychloroquine and remdesivir and how ADR reporting fluctuated during the COVID-19 pandemic. Methods: A retrospective observational study was conducted utilizing the Food and Drug Administration's Adverse Event Reporting System (FAERS) data between 2019 and 2021. The study was conducted in two phases. In the first phase, all reports associated with the drugs of interest were evaluated to assess all related adverse drug reactions. In the second phase, specific outcomes of interest (i.e., QT prolongation and renal and hepatic events) were determined to study their association with the drugs of interest. A descriptive analysis was conducted for all adverse reactions related to the drugs being studied. In addition, disproportionality analyses were conducted to compute the reporting odds ratio, the proportional reporting ratio, the information component, and the empirical Bayes geometric mean. All analyses were conducted using RStudio. Results: A total of 9,443 ADR reports related to hydroxychloroquine; 6,160 (71.49) patients were female, and higher percentage of patients of both sexes were over the age of 65 years. QT prolongation (1.48%), pain (1.38%), and arthralgia (1.25%) were most frequently reported ADRs during the COVID-19 pandemic. The association of QT prolongation with use of hydroxychloroquine was statistically significant (ROR 47.28 [95% CI 35.95-62.18]; PRR 42.41 [95% CI 32.25-55.78]; EBGM 16.08; IC 4.95) compared with fluoroquinolone. The outcome was serious medical events in 48.01% of ADR reports; 27.42% required hospitalization and 8.61% resulted in death. Of 6,673 ADR reports related to remdesivir, 3,928 (61.13%) patients were male. During 2020, the top three ADR reports were elevated liver function tests (17.26%), acute kidney injury (5.95%) and death (2.84%). Additionally, 42.71% of ADR reports indicated serious medical events; 19.69% resulted in death and 11.71% indicated hospitalization. The ROR and PRR of hepatic and renal events associated with remdesivir were statistically significant, (4.81 [95% CI 4.46-5.19] and 2.96 [95% CI 2.66-3.29], respectively. Conclusion: Our study showed that several serious ADRs were reported with the use of hydroxychloroquine, which resulted in hospitalization and death. Trends with the use of remdesivir were similar, but to a lesser extent. Therefore, this study showed us that off-label use should be based on thorough evidence-based evaluation.

Serially Combining Epidemiological Designs Does Not Improve Overall Signal Detection in Vaccine Safety Surveillance.

INTRODUCTION: Vaccine safety surveillance commonly includes a serial testing approach with a sensitive method for 'signal generation' and specific method for 'signal validation.' The extent to which serial testing in real-world studies improves or hinders overall performance in terms of sensitivity and specificity remains unknown. METHODS: We assessed the overall performance of serial testing using three administrative claims and one electronic health record database. We compared type I and II errors before and after empirical calibration for historical comparator, self-controlled case series (SCCS), and the serial combination of those designs against six vaccine exposure groups with 93 negative control and 279 imputed positive control outcomes. RESULTS: The historical comparator design mostly had fewer type II errors than SCCS. SCCS had fewer type I errors than the historical comparator. Before empirical calibration, the serial combination increased specificity and decreased sensitivity. Type II errors mostly exceeded 50%. After empirical calibration, type I errors returned to nominal; sensitivity was lowest when the methods were combined. CONCLUSION: While serial combination produced fewer false-positive signals compared with the most specific method, it generated more false-negative signals compared with the most sensitive method. Using a historical comparator design followed by an SCCS analysis yielded decreased sensitivity in evaluating safety signals relative to a one-stage SCCS approach. While the current use of serial testing in vaccine surveillance may provide a practical paradigm for signal identification and triage, single epidemiological designs should be explored as valuable approaches to detecting signals.

Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: reviewed for evidence-based integrity and endorsed by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

BACKGROUND: To develop evidence-based clinical practice guidelines on venous thromboembolism (VTE) prevention in adults with trauma in inpatient settings. METHODS: The Saudi Critical Care Society (SCCS) sponsored guidelines development and included 22 multidisciplinary panel members who completed conflict-of-interest forms. The panel developed and answered structured guidelines questions. For each question, the literature was searched for relevant studies. To summarize treatment effects, meta-analyses were conducted or updated. Quality of evidence was assessed using the Grading Recommendations, Assessment, Development, and Evaluation (GRADE) approach, then the evidence-to-decision (EtD) framework was used to generate recommendations. Recommendations covered the following prioritized domains: timing of pharmacologic VTE prophylaxis initiation in non-operative blunt solid organ injuries; isolated blunt traumatic brain injury (TBI); isolated blunt spine trauma or fracture and/or spinal cord injury (SCI); type and dose of pharmacologic VTE prophylaxis; mechanical VTE prophylaxis; routine duplex ultrasonography (US) surveillance; and inferior vena cava filters (IVCFs). RESULTS: The panel issued 12 clinical practice recommendations-one, a strong recommendation, 10 weak, and one with no recommendation due to insufficient evidence. The panel suggests starting early pharmacologic VTE prophylaxis for non-operative blunt solid organ injuries, isolated blunt TBIs, and SCIs. The panel suggests using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) and suggests either intermediate-high dose LMWH or conventional dosing LMWH. For adults with trauma who are not pharmacologic candidates, the panel strongly recommends using mechanical VTE prophylaxis with intermittent pneumatic compression (IPC). The panel suggests using either combined VTE prophylaxis with mechanical and pharmacologic methods or pharmacologic VTE prophylaxis alone. Additionally, the panel suggests routine bilateral lower extremity US in adults with trauma with elevated risk of VTE who are ineligible for pharmacologic VTE prophylaxis and suggests against the routine placement of prophylactic IVCFs. Because of insufficient evidence, the panel did not issue any recommendation on the use of early pharmacologic VTE prophylaxis in adults with isolated blunt TBI requiring neurosurgical intervention. CONCLUSION: The SCCS guidelines for VTE prevention in adults with trauma were based on the best available evidence and identified areas for further research. The framework may facilitate adaptation of recommendations by national/international guideline policymakers.

Estimating the potential economic impact of the Wasfaty program on costs of antidiabetic treatment: An initiative for the digital transformation of health.

Introduction: The Saudi health care transformation is taking place through the implementation of many initiatives and programs to serve Saudi Vision 2030, which aims to improve health care services by focusing on digitalization and privatization. This study aimed to evaluate the economic impact of implementing the new digital health transformation initiative (Wasfaty service) on the health care budget using diabetes mellitus as an example. Methods: This study presents a cost analysis evaluation following the implementation of the Wasfaty program during the period between 2017 and 2021. The study compared the pre-Wasfaty period and the Wasfaty period in terms of direct medical costs. Data sources were the Ministry of Health for pre-Wasfaty data and the National Unified Procurement Company, which runs the Wasfaty program, for Wasfaty data. The study focuses on diabetic medications for outpatients. This health economic evaluation used the cost per visit, and sensitivity analyses were conducted utilizing the cost per patient according to the prevalence of diabetes mellitus. Results: After implementing the transformation using the Wasfaty service, the estimated annual mean cost savings per visit were USD 109.18 (SAR 409.43), and the cost savings per patient with a prevalence of 11% were USD 13.89 (SAR 52.1). The saving costs were USD 11,750,600 (SAR 44,064,750) for human resources and USD 97,473,469 (SAR 365,525,508) for pharmacies' operation costs without including warehouse expenditures. The savings from the clinical decision support system preventing undesirable medication costs were estimated at USD 9,842,720 (SAR 36,910,201), and savings from the prevention of undesirable adverse events were estimated at USD 137,332,615 (SAR 514,997,308) for a 6% prediction. The total healthcare expenditure savings were USD 258,762,981 to 274,972,971 (SAR 970,361,178 ± 1,031,148,640). Conclusions: Implementing the new digitization and privatization initiatives (i.e., the Wasfaty program) as a result of the transformation in the health care sector had led to a significant reduction in health care expenditures and cost savings with respect to clinical and pharmacy services using diabetes mellitus as an example.

Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: reviewed for evidence-based integrity and endorsed by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine

To develop evidence-based clinical practice guidelines on venous thromboembolism (VTE) prevention in adults with trauma in inpatient settings. The Saudi Critical Care Society (SCCS) sponsored guidelines development and included 22 multidisciplinary panel members who completed conflict-of-interest forms. The panel developed and answered structured guidelines questions. For each question, the literature was searched for relevant studies. To summarize treatment effects, meta-analyses were conducted or updated. Quality of evidence was assessed using the Grading Recommendations, Assessment, Development, and Evaluation (GRADE) approach, then the evidence-to-decision (EtD) framework was used to generate recommendations. Recommendations covered the following prioritized domains: timing of pharmacologic VTE prophylaxis initiation in non-operative blunt solid organ injuries; isolated blunt traumatic brain injury (TBI); isolated blunt spine trauma or fracture and/or spinal cord injury (SCI); type and dose of pharmacologic VTE prophylaxis; mechanical VTE prophylaxis; routine duplex ultrasonography (US) surveillance; and inferior vena cava filters (IVCFs). The panel issued 12 clinical practice recommendations­one, a strong recommendation, 10 weak, and one with no recommendation due to insufficient evidence. The panel suggests starting early pharmacologic VTE prophylaxis for non-operative blunt solid organ injuries, isolated blunt TBIs, and SCIs. The panel suggests using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) and suggests either intermediate­high dose LMWH or conventional dosing LMWH. For adults with trauma who are not pharmacologic candidates, the panel strongly recommends using mechanical VTE prophylaxis with intermittent pneumatic compression (IPC). The panel suggests using either combined VTE prophylaxis with mechanical and pharmacologic methods or pharmacologic VTE prophylaxis alone. Additionally, the panel suggests routine bilateral lower extremity US in adults with trauma with elevated risk of VTE who are ineligible for pharmacologic VTE prophylaxis and suggests against the routine placement of prophylactic IVCFs. Because of insufficient evidence, the panel did not issue any recommendation on the use of early pharmacologic VTE prophylaxis in adults with isolated blunt TBI requiring neurosurgical intervention. The SCCS guidelines for VTE prevention in adults with trauma were based on the best available evidence and identified areas for further research. The framework may facilitate adaptation of recommendations by national/international guideline policymakers.

Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.

Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. Funding: None.

Association between proton pump inhibitors and rhabdomyolysis risk: a post-marketing surveillance using FDA adverse event reporting system (FAERS) database.

Background: This research aims to explore and compare the signals of rhabdomyolysis from the use of Proton pump inhibitors (PPIs) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Rhabdomyolysis and related terms submitted between 2013 and 2021 were retrieved from the FAERS database. The data were analyzed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Empirical Bayes Geometric Mean (EBGM) and the information component (IC). The signals of rhabdomyolysis associated with PPIs use were detected in both 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) utilizers and non-utilizers. Results: A total of 7,963,090 reports were retrieved and analyzed. Fifty-seven reports linked PPIs to rhabdomyolysis out of 3670 reports from other drugs (non-statin included). The association of rhabdomyolysis and PPIs was significant in both statins included, and non-statin-included reports, although with varying degrees of association. The ROR was 2.5 (95% confidence interval [CI] 1.9-3.2) for PPIs in non-statin-included reports and 2 (95% CI: 1.5-2.6) for PPIs in statin-included reports. Conclusion: Significant signals of rhabdomyolysis were associated with PPIs. However, its signals were higher in non-statin-included reports compared to statin-included reports. Plain Language Summary: Plain language summaryProton Pump Inhibitors and rhabdomyolysis risk Background: The FDA created the FDA Adverse Event Reporting System (FAERS) database to support post-marketing surveillance programs. The FAERS is a computerized database with more than nine million adverse event reports, including all reports from 1969 to the present. This research aims to explore and compare the signals of rhabdomyolysis from the use of proton pump inhibitors (PPIs) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.Research design and methods: We retrieved rhabdomyolysis and related terms submitted between 2013 and 2021 from the FAERS database. Then, we analyzed the data that we found. We detected the signals of rhabdomyolysis associated with PPIs use in both statins utilizers and non-utilizers.Results: We retrieved and analyzed a total of 7,963,090 reports. We found 57 reports linked PPIs to rhabdomyolysis out of 3670 reports from other drugs (non-statin included). The association of rhabdomyolysis and PPIs was significant in both statins included, and non-statin-included reports, although with varying degrees of association.Conclusion: Significant signals of rhabdomyolysis were associated with PPIs. However, its signals were higher in non-statin-included reports than in statin-included reports.

Impact of risk communication on patient's safety during the pandemic.

More than 2 years has passed since the pandemic was declared in 2019 due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was later declared to be the pathogen causing coronavirus disease 2019 (COVID-19). During this time, many healthcare systems faced numerous challenges to control the high morbidity and mortality of the disease. Unlike previous pandemics, the actions against this pandemic started quickly on both the global and country levels. These actions were, scientifically, to study the virus as well as transmission process and to develop medications and vaccines against it. Also, we had to protect people from transmission by knowing how best to apply precautionary methods. However, there were some unexpected negative consequences of the pandemic and one of those the World Health Organization (WHO) called 'infodemic'. This term infodemic refers to the manipulation of a population's behavior in the assessment of information (or, more accurately, lack of assessment) related to the use of medications, particularly vaccines. Unfortunately, even with positive development in science, there was limited and often contradictory amount of information on the safety and efficacy profile of drugs and vaccines. Therefore, this made it harder for public health agencies to determine the impact of the incidence of adverse reactions and events associated with interventions such as vaccines. Hence, risk communication needs to be emphasized during any pandemic, as ignoring risk communications to different stakeholders could undermine all well-intended therapeutic interventions. Given this, it is important that the different stakeholders involved (health authorities, societies, healthcare professionals, etc.) assess the different behavioral patterns within their respective populations and propose appropriate strategies to act. Such an approach complement having risk management and communication plans for this and future pandemics. The aim of this article is to explore how information management, risk management, and risk communication during the pandemic can provide valuable lessons for the future. Plain language summary: Impact of risk communication on patient's safety during the pandemic More than 2 years have gone by since the pandemic was declared in 2019 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many challenges have been confronted by the healthcare system during this time to control the high impact of this disease. This pandemic, unlike others that humanity has faced, is characterized by a special feature: today, we have an enormous amount of information only a click away. This situation has been of great benefit to humanity and has allowed the development of science; nevertheless, misinformation (infodemics) has been a major problem, which has revealed the behavior of the population regarding the evaluation of information (or better, lack of assessment) related to the use of medications and particularly of vaccines. Given this, it is important that the different people involved (health authorities, societies, healthcare professionals, etc.) assess the behavior and propose appropriate strategies to act and have plans for this and future pandemics. This article intends to explore from the authors' perspective how information management, risk management, and risk communication during the pandemic can provide valuable lessons for the future.

Recording type 2 diabetes mellitus in a standardised central Saudi database: a retrospective validation study.

OBJECTIVES: This study was conducted to assess the validity of recording (and the original diagnostic practice) of type 2 diabetes mellitus at a hospital whose records were integrated to a centralised database (the standardised common data model (CDM) of the Saudi National Pharmacoepidemiologic Database (NPED)). DESIGN: A retrospective single-centre validation study. SETTINGS: Data of the study participants were extracted from the CDM of the NPED (only records of one tertiary care hospital were integrated at the time of the study) between 1 January 2013 and 1 July 2018. PARTICIPANTS: A random sample of patients with type 2 diabetes mellitus (≥18 years old and with a code of type 2 diabetes mellitus) matched with a control group (patients without diabetes) based on age and sex. OUTCOME MEASURES: The standardised coding of type 2 diabetes in the CDM was validated by comparing the presence of diabetes in the CDM versus the original electronic records at the hospital, the recording in paper-based medical records, and the physician re-assessment of diabetes in the included cases and controls, respectively. Sensitivity, specificity, positive predictive value and negative predictive value were estimated for each pairwise comparison using RStudio V.1.4.1103. RESULTS: A total of 437 random sample of patients with type 2 diabetes mellitus was identified and matched with 437 controls. Only 190 of 437 (43.0%) had paper-based medical records. All estimates were above 90% except for sensitivity and specificity of CDM versus paper-based records (54%; 95% CI 47% to 61% and 68%; 95% CI 62% to 73%, respectively). CONCLUSIONS: This study provided an assessment to the extent of which only type 2 diabetes mellitus code can be used to identify patients with this disease at a Saudi centralised database. A future multi-centre study would help adding more emphasis to the study findings.

Pharmacovigilance regulatory actions by national pharmacovigilance centers in Arab countries following COVID-19 pandemic.

BACKGROUND: Pharmacovigilance (PV) activities were affected by COVID-19. Therefore, several health authorities around the world have issued guidelines and practices to ensure that PV activities are maintained and continued during the pandemic. This study aimed to assess the impact of COVID-19 on the preparedness and performance of national PV systems in 14 Arab countries. RESEARCH DESIGN AND METHODS: This was a cross-sectional study that was conducted between July and October 2020. National PV centers in 18 Arab countries were invited to participate in this study. Descriptive analysis was used to summarize and present the results of this study. RESULTS: Responses were obtained from 14 (77.8%) countries. Adverse events reporting was the main PV activity that was covered by PV guidelines and practices. National guidelines and practices covered other PV activities in 8 (57.14%) of the participating countries. Performance and practices of national PV centers vary considerably among participating countries during the pandemic. CONCLUSION: The findings highlight the differences in preparedness and performance of different national PV centers in participating Arab countries. Improving digital infrastructure among participating countries could serve as a useful tool to minimize the impact of the pandemic on PV activities.

Corrigendum: Vaccine safety surveillance using routinely collected healthcare data-An empirical evaluation of epidemiological designs.

[This corrects the article DOI: 10.3389/fphar.2022.893484.].

Health economic burden of COVID-19 in Saudi Arabia.

Background: The coronavirus disease 2019 (COVID-19) pandemic has added a massive economic burden on health care systems worldwide. Saudi Arabia is one of the numerous countries that have been economically affected by this pandemic. The objective of this study was to provide real-world data on the health economic burden of COVID-19 on the Saudi health sector and assess the direct medical costs associated with the management of COVID-19. Methods: A retrospective cohort study was conducted based on data collected from patients hospitalized with COVID-19 across 10 institutions in eight different regions in Saudi Arabia. The study calculated the direct medical costs of all cases during the study period by using SAS statistical analysis software. These costs included costs directly related to medical services, such as the health care treatment, hospital stays, laboratory investigations, treatment, outcome, and other related care. Results: A total of 5,286 adult patients admitted with COVID-19 during the study period were included in the study. The average age of the patients was 54 years, and the majority were male (79%). Among the COVID-19 patients hospitalized in a general ward, the median hospital length of stay was 5.5 days (mean: 9.18 days), while the ICU stay was 4.2 days (mean: 7.94 days). The total medical costs for general ward and ICU patients were US$ 38,895 and US$ 24,207,296.9, respectively. The total laboratory investigations ranked as the highest-cost services US$ 588,975 followed by treatment US$ 3,886,509.8. Overall, the total cost of all medical services for patients hospitalized with COVID-19 was US$ 51,572,393.4. Conclusion: This national study found that COVID-19 was not only a serious concern for patients but also a serious economic burden on the health care system in Saudi Arabia.

Vaccine Safety Surveillance Using Routinely Collected Healthcare Data-An Empirical Evaluation of Epidemiological Designs.

Background: Routinely collected healthcare data such as administrative claims and electronic health records (EHR) can complement clinical trials and spontaneous reports to detect previously unknown risks of vaccines, but uncertainty remains about the behavior of alternative epidemiologic designs to detect and declare a true risk early. Methods: Using three claims and one EHR database, we evaluate several variants of the case-control, comparative cohort, historical comparator, and self-controlled designs against historical vaccinations using real negative control outcomes (outcomes with no evidence to suggest that they could be caused by the vaccines) and simulated positive control outcomes. Results: Most methods show large type 1 error, often identifying false positive signals. The cohort method appears either positively or negatively biased, depending on the choice of comparator index date. Empirical calibration using effect-size estimates for negative control outcomes can bring type 1 error closer to nominal, often at the cost of increasing type 2 error. After calibration, the self-controlled case series (SCCS) design most rapidly detects small true effect sizes, while the historical comparator performs well for strong effects. Conclusion: When applying any method for vaccine safety surveillance we recommend considering the potential for systematic error, especially due to confounding, which for many designs appears to be substantial. Adjusting for age and sex alone is likely not sufficient to address differences between vaccinated and unvaccinated, and for the cohort method the choice of index date is important for the comparability of the groups. Analysis of negative control outcomes allows both quantification of the systematic error and, if desired, subsequent empirical calibration to restore type 1 error to its nominal value. In order to detect weaker signals, one may have to accept a higher type 1 error.