Pharmacoepidemiology and Drug Safety最新文献

Purpose: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare autoimmune condition of the peripheral nervous system. The validity of the CIDP diagnosis code in claims data is unclear.

Methods: We conducted a validation study testing the performance of claims-based algorithms in identifying CIDP cases, using electronic health record data from the Mass General Brigham Integrated Health Care System linked with Medicare claims data from 01/01/2008 to 12/31/2020. The algorithms require a record of intravenous immunoglobulin (IVIG) use and International Classification of Diseases 9th/10th Revision (ICD9/10) CIDP codes before (including) the date of IVIG use. The positive predictive values (PPVs) of each claims-based algorithm were calculated against the reference standard for CIDP and chronic immune-mediated acquired neuropathy established through chart review by two board-certified neurologists using a standardized abstraction tool.

Results: The study cohort consisted of 140 patients (59 in the ICD9 and 81 in the ICD10 era). The PPV of the algorithm requiring at least one CIDP diagnosis code before IVIG use was 66.2% (95% confidence interval [CI], 58.0-74.3). The PPV improved to 71.2% (62.7-79.6) when requiring at least two CIDP codes before IVIG use. The PPV for patients with at least one CIDP code who met the European Academy of Neurology/Peripheral Nerve Society 2021 diagnostic criteria was 30.0% (22.1-37.9).

Conclusion: We found that a patient cohort identified using claims-based CIDP diagnoses included a substantial number of patients with other chronic inflammatory acquired neuropathies not formally recognized as CIDP by clinical consensus criteria. Requiring two CIDP codes can improve PPVs.

Purpose: Immune globulin infusion (human) 10% solution (GAMMAGARD LIQUID; GGL), an intravenous immunoglobulin (IVIG), has recently received U.S. approval for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We evaluated thrombotic events, acute kidney injury (AKI), and hemolytic events among patients with CIDP initiating IVIG treatment with GGL, versus a U.S.-approved IVIG comparator for CIDP, in individual and combined cohorts of immunoglobulin (Ig)-naive and Ig-experienced participants.

Methods: This active-comparator, new-user, cohort study of patients with CIDP used the Merative MarketScan Research and Optum Clinformatics Data Mart databases (2008-2019). Outcomes were compared between adults receiving GGL and comparator IVIGs within propensity score-weighted samples using hazard ratios (HRs) and time period-specific risk ratios (RRs) and risk differences (RDs) with 95% confidence intervals (CI). Database-specific results were meta-analyzed and appropriate.

Results: Data from eligible patients in MarketScan (GGL, n = 1441; comparators, n = 2708) and Optum (GGL, n = 644; comparators, n = 1293) were analyzed. Across both databases, HRs, 1-year RRs, and 1-year RDs for thrombotic events did not suggest consistent differences in risk across treatment groups (e.g., MarketScan combined cohort: RR 1.14 [95% CI, 0.50 to 2.55]; Optum combined cohort: 0.60 [0.25 to 1.54]). Similarly, there was no difference in AKI risk between groups (e.g., MarketScan combined cohort: RR 1.25 [95% CI, 0.65 to 2.54]; Optum combined cohort: 0.65 [0.22 to 1.94]). Hemolytic events were rare.

Conclusions: Thrombotic events, AKI, and hemolytic events were rare among patients with CIDP receiving IVIG. There were no consistently different outcome risks between patients receiving GGL versus other IVIGs with US approval for CIDP.

Background: International harmonization of real-world data and evidence (RWD/E) standards is a goal among real-world data/real-world evidence (RWD/E) policy stakeholders. The Duke-Robert J. Margolis Institute for Health Policy developed an online 'International Harmonization of RWE Standards Dashboard' to provide timely updates around these goals.

Methods: Guidance for industry (draft and final) and related literature available online by medical product regulators globally was sought and, where needed, translated into English language using a certified translator. Consultations were then held with practicing experts to identify, collate, and interpret documents. An online Tableau tool was assembled to collate guidance documents and regulatory definitions of the following key terms used among the community to describe fit-for-use RWE in regulatory submissions: relevance, reliability, and quality.

Results: As of February 2025, the United States Food and Drug Administration (FDA) has released the most RWE guidance documents to date (n = 13; 4 draft, 9 final). Four (4) regulators globally (US FDA, EMA, Taiwan FDA, Brazil ANVISA) have directly defined at least two (2) out of the three key terms (reliability, relevance, quality), indicating alignment around the importance of these terms used in the context of RWD/E. Across these terms, we propose areas of definitional alignment: data representativeness and research and regulatory concern (relevance), accuracy in data interpretation and quality and integrity during data accrual (reliability), and data quality assurance across sites and time (quality). We propose areas of definitional misalignment regarding clinical context, data availability and representativeness, and ensuring study sample sizes and/or datasets are adequate to address a given study question.

Conclusions: Our assessment of definitions provided among these four regulators lends us to propose distinct areas for harmonization based on our assessment of where regulators appear to align and highlight opportunities to address misalignment.

Data from sources other than traditional randomized clinical trials are known as real-world data (RWD), and the evidence derived from the review and analysis of RWD is known as real-world evidence (RWE). RWD and RWE are used increasingly throughout the lifecycle of medicinal products to provide evidence about their effectiveness and safety. Recent regulatory guidance about RWE and approvals based on the use of RWE to demonstrate beneficial effects of products have created an urgency to develop generally accepted processes that promote trust in the evidence-generation process. A recent report from a working group of the Council for International Organizations of Medical Science (CIOMS) describes the use of RWE for decision making in the lifecycle of medical products, describes RWD and data sources, discusses key scientific considerations in the generation of RWE, and discusses ethical and governance issues related to the use of RWD. This paper provides a high-level summary of this report. More work remains to be done to globally harmonize practices and guidance for using RWD and RWE for regulatory decision making, thereby maximizing the benefits they can bring to patient care and public health.

Background: Direct Healthcare Professional Communications (DHPCs) are an important risk minimisation measure. Their effect has been shown to be variable and has been measured using different outcomes and study populations. Depending on the content of the message, the optimal outcome to measure a direct effect of the DHPC can differ. This systematic review investigates whether the effects of DHPCs differ according to the use of proximal outcomes and the inclusion of the targeted population.

Methods: EMBASE and MEDLINE were searched for European DHPC effectiveness studies performed up to April 6, 2022, evaluating the impact of DHPCs issued from 2008. Outcomes and their impact were extracted, together with a classification of the message. The outcomes were categorised as knowledge/awareness, self-reported behaviour (prescribing/monitoring), prescribing of medication (including dosage changes), monitoring, or adverse events/other health outcomes, including hospitalisation. The outcomes closest to the message of the DHPC were defined as proximal. Outcomes were coded 1 when effective and 0 if not. If multiple outcomes were reported in a study, a composite outcome was created ranging from 0 to 1. Chi-square or Fisher exact tests were performed.

Results: From 7063 (scientific) publications identified in our literature search, 60 publications evaluating 31 different DHPCs were selected for our review. As publications could study multiple messages with an outcome, from the 60 scientific publications, 103 outcomes were generated for the messages, of which 30 had a high impact on the composite outcome, with the proportion of analyses with a significant association between 0.75 and 1. When taking the target population into account, some messages were studied in more than one population, resulting in 115 outcomes, of which 33 had a high impact, that is, a composite outcome between 0.75 and 1.

Conclusion: Neither the use of proximal outcomes nor the restriction of the analysis to the targeted population significantly influenced the impact observed of the DHPC. These results stress the need for improving drug safety communication.

Purpose: To assess the effect of deregulating the national sales reporting system on Brazilian pharmacoepidemiologic data on antidepressants.

Methods: This was a time series analysis to assess the trends in antidepressant sales in Brazilian drugstores from January 2014 to December 2022 using the Brazilian National Controlled Products Management System (SNGPC) and to predict sales records for 2022 after the deregulation of the mandatory record in December 2021. Antidepressant sales were converted to defined daily doses per 1000 inhabitants per day (DID). The seasonal autoregressive integrated moving average (SARIMA) was used to predict sales records for 2022. All analyses were conducted in Stata v.14.2.

Results: Sales of patients taking antidepressants increased significantly from 2014 (mean: 14.7 DID/month) to 2020 (mean: 33.5 DID/month; β = 0.231; p < 0.001). After the start of the COVID-19 pandemic, the increasing trend continued, but the change was not significant (β = 0.330; p = 0.130). After the deregulation, a sharp decrease was observed (β = -1.032; p < 0.001). The monthly antidepressant sales forecasted for 2022 were 36.5 DID, while the observed value was 2.5 DID.

Conclusion: Deregulation of SNGPC registration significantly decreased the number of antidepressant sales records. This measure affected the availability of pharmacoepidemiological data and research in Brazil.

Purpose: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly prescribed, but their adverse effects may prompt new drug prescription(s), known as prescribing cascades (PCs). We aimed to identify potential ACEI-induced PCs using high-throughput sequence symmetry analysis.

Methods: Using claims data from a national sample of Medicare beneficiaries (2011-2020), we identified new ACEI users aged ≥ 66 years with continuous enrollment ≥ 360 days before and ≥ 180 days after ACEI initiation. We screened for initiation of 446 other (non-antihypertensive) "marker" drug classes within ±90 days of ACEI initiation, generating sequence ratios (SRs) reflecting proportions of ACEI users starting the marker class after versus before ACEI initiation. Adjusted SRs (aSRs) accounted for prescribing trends over time. For significant aSRs, we calculated the naturalistic number needed to harm (NNTH), and significant signals underwent clinical review for plausibility.

Results: We identified 308 579 ACEI initiators (mean age 76.1 ± 7.5 years; 59.6% female; 88.6% with hypertension). Of 446 marker classes evaluated, 81 signals were significant, and 42 (52%) classified as potential PCs after clinical review. The strongest signals ranked by lowest NNTH included corticosteroids (NNTH 313; 95% CI, 262-392) and serotonin type 3 (5-HT₃) antagonists (NNTH 496; 95% CI, 392-689); the strongest signals ranked by highest aSR included sympathomimetics (aSR, 1.97; 95% CI, 1.10-3.53) and other antianemic preparations (aSR, 1.87; 95% CI, 1.31-2.67).

Conclusion: Identified prescribing cascade signals were indicative of known and possibly underrecognized ACEI adverse events in this Medicare cohort. The findings are hypothesis-generating and require further investigation to determine the extent and impact of the identified PCs on health outcomes.