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Use of Real-World Data and Real-World Evidence in Rare Disease Drug Development: A Statistical Perspective.
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-04-01 Epub Date: 2025-02-14 DOI: 10.1002/cpt.3576
Jie Chen, Susan Gruber, Hana Lee, Haitao Chu, Shiowjen Lee, Haijun Tian, Yan Wang, Weili He, Thomas Jemielita, Yang Song, Roy Tamura, Lu Tian, Yihua Zhao, Yong Chen, Mark van der Laan, Lei Nie

Real-world data (RWD) and real-world evidence (RWE) have been increasingly used in medical product development and regulatory decision-making, especially for rare diseases. After outlining the challenges and possible strategies to address the challenges in rare disease drug development (see the accompanying paper), the Real-World Evidence (RWE) Scientific Working Group of the American Statistical Association Biopharmaceutical Section reviews the roles of RWD and RWE in clinical trials for drugs treating rare diseases. This paper summarizes relevant guidance documents and frameworks by selected regulatory agencies and the current practice on the use of RWD and RWE in natural history studies and the design, conduct, and analysis of rare disease clinical trials. A targeted learning roadmap for rare disease trials is described, followed by case studies on the use of RWD and RWE to support a natural history study and marketing applications in various settings.

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引用次数: 0
Risk of Hypoglycemia Associated With Concomitant Use of Insulin Secretagogues and ACE Inhibitors in Adults With Type 2 Diabetes: A Systematic Review. 成人2型糖尿病患者同时使用胰岛素分泌剂和ACE抑制剂与低血糖风险相关:一项系统综述
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-04-01 Epub Date: 2024-12-13 DOI: 10.1002/cpt.3530
Patricia Y Chu, Emma K Edmondson, James H Flory, Jing Huang, Sean Hennessy

Insulin secretagogues and angiotensin-converting enzyme inhibitors (ACEIs) are commonly co-prescribed for patients with type 2 diabetes (T2D). Case reports suggesting that co-administration of insulin secretagogues with ACEIs is associated with an increased risk of serious hypoglycemia have led to warnings regarding a drug-drug interaction in widely used drug compendia. However, subsequent studies have had inconsistent results. We performed a systematic review to evaluate the evidence that concomitant use of ACEIs and insulin secretagogues increases the risk of serious hypoglycemia. MEDLINE/PubMed and Embase were searched from inception to July 2023 for studies evaluating adults with T2D treated with insulin secretagogues, such as sulfonylureas or meglitinides, and exposed to an ACEI. The primary outcome was serious hypoglycemia. A literature search yielded 472 papers, of which five met the inclusion criteria. The heterogeneity of the studies precluded meta-analysis. Two studies using multiple methods to address bias found no association between hypoglycemia and concomitant use of ACEI and insulin secretagogues. Three studies found potential associations, but only one was statistically significant; these studies were at serious or critical risk of bias due to potential confounding from lack of adjustment for renal dysfunction. The higher quality studies found no association between the concomitant use of insulin secretagogues with ACEI and hypoglycemia. Drug compendia and electronic health records should consider updating and removing alerts warning of a drug-drug interaction between insulin secretagogues as a class and ACEIs.

胰岛素分泌剂和血管紧张素转换酶抑制剂(ACEIs)通常是2型糖尿病(T2D)患者的合用处方。病例报告表明,胰岛素促分泌剂与乙酰胆碱抑制剂联合使用与严重低血糖的风险增加有关,这导致了广泛使用的药物纲要中关于药物相互作用的警告。然而,随后的研究得出了不一致的结果。我们进行了一项系统回顾,以评估ACEIs和胰岛素分泌剂同时使用会增加严重低血糖风险的证据。MEDLINE/PubMed和Embase从成立到2023年7月检索了评估胰岛素分泌剂(如磺脲类或美格列内酯)治疗成人T2D并暴露于ACEI的研究。主要结局是严重低血糖。文献检索得到472篇论文,其中5篇符合纳入标准。研究的异质性妨碍了meta分析。两项采用多种方法解决偏倚的研究发现,低血糖与同时使用ACEI和胰岛素分泌剂之间没有关联。三项研究发现了潜在的关联,但只有一项具有统计学意义;由于缺乏对肾功能障碍的调整,这些研究存在严重或严重的偏倚风险。高质量的研究发现胰岛素促分泌剂与ACEI合用与低血糖之间没有关联。药物纲要和电子健康记录应考虑更新和删除警告,警告胰岛素分泌剂作为一类与acei之间的药物-药物相互作用。
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引用次数: 0
Investigational Use of Real-World Data as a Hybrid Control in Pancreatic Ductal Adenocarcinoma From the Randomized Phase Ib/II MORPHEUS Trial. 随机Ib/II期MORPHEUS试验中使用真实世界数据作为胰腺导管腺癌混合对照的研究
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-04-01 Epub Date: 2024-12-20 DOI: 10.1002/cpt.3528
Andrew H Ko, Do-Youn Oh, Janet Lau, Shivani K Mhatre, Bo Ci, Robson Machado, Shi Li, Michael T Bretscher, Irmarie Reyes-Rivera, Jiawen Zhu, Xiaosong Zhang, Jilpa Patel, Matthew A Psioda, Mariano Ponz-Sarvise

Enrolling adequate numbers of patients into the control arm of randomized controlled trials (RCTs) often presents barriers. There is interest in leveraging real-world data (RWD) from electronic health records (EHRs) to construct external control (EC) arms to supplement RCT control arms and form hybrid control (HC) arms. This investigation showed the use of an HC arm in second-line metastatic pancreatic ductal adenocarcinoma (PDAC). The RCT experimental arm (atezolizumab + PEGylated recombinant human hyaluronidase (Atezo + PEGPH20)) was compared with an HC arm consisting of patients treated with modified FOLFOX6 or gemcitabine/nab-paclitaxel from the MORPHEUS PDAC internal control arm supplemented with data from a nationwide EHR-derived de-identified database as the EC arm. The EC arm was constructed by applying key inclusion/exclusion criteria from the MORPHEUS PDAC trial to patients from the real-world cohort. Baseline variables were balanced using propensity score matching and covariate adjustment. Three analysis approaches-Cox model with pooled-control data, Cox model with control arm-specific frailty, and Bayesian analysis using a commensurate prior-were assessed. Overall survival was similar between the treatment arms. The direction and magnitude of hazard ratios (HRs) from the multiple HC analyses (HRs ranged from 1.02 to 1.06) were comparable with the reported trial HR (HR 0.91; 95% CI: 0.56, 1.49). This analysis demonstrates the feasibility and applicability of leveraging RWD in clinical trial design to supplement clinical trial control arms.

将足够数量的患者纳入随机对照试验(RCTs)的对照组通常存在障碍。人们对利用来自电子健康记录(EHRs)的真实世界数据(RWD)来构建外部控制(EC)臂来补充RCT控制臂并形成混合控制(HC)臂很感兴趣。本研究显示HC臂在二线转移性胰腺导管腺癌(PDAC)中的应用。RCT实验组(atezolizumab +聚乙二醇化重组人透明质酸酶(Atezo + PEGPH20))与HC组进行比较,HC组由来自MORPHEUS PDAC内部对照组的改良FOLFOX6或吉西他滨/nab-紫杉醇治疗的患者组成,并辅以来自全国ehr衍生的去识别数据库的数据作为EC组。EC组是通过将MORPHEUS PDAC试验的关键纳入/排除标准应用于来自现实世界队列的患者而构建的。使用倾向评分匹配和协变量调整平衡基线变量。评估了三种分析方法-合并对照数据的Cox模型,对照臂特异性脆弱性的Cox模型和使用相应先验的贝叶斯分析。治疗组之间的总生存率相似。多重HC分析得出的风险比(HR)的方向和大小(HR范围为1.02 ~ 1.06)与报道的试验HR (HR 0.91;95% ci: 0.56, 1.49)。这一分析证明了在临床试验设计中利用RWD补充临床试验对照组的可行性和适用性。
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引用次数: 0
Population-Based Validation Results From the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) Study.
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-04-01 Epub Date: 2025-02-11 DOI: 10.1002/cpt.3583
Rishi J Desai, Vijay R Varma, Mufaddal Mahesri, Su Been Lee, Ariel Freedman, Tobias Gerhard, Jodi Segal, Seanna Vine, Mary Beth E Ritchey, Daniel B Horton, Madhav Thambisetty

We evaluated whether drugs approved for other indications that also target metabolic drivers of Alzheimer's disease and related dementia (ADRD) pathogenesis are associated with delayed onset of ADRD. Using routinely collected healthcare data from two population-based data sources from the US (Medicare) and UK (CPRD), we conducted active comparator, new-user cohort studies. Four alternate analytic and design specifications were implemented: (1) an as-treated follow-up approach, (2) an as-started follow-up approach incorporating a 6-month induction period, (3) incorporating a 6-month symptom to diagnosis period to account for misclassification of ADRD onset, and (4) identifying ADRD through symptomatic prescriptions and diagnosis codes. Of the 10 drug pairs evaluated, hydrochlorothiazide vs. dihydropyridine CCBs showed meaningful reductions in 3 out of 4 analyses that addressed specific biases including informative censoring, reverse causality, and outcome misclassification (pooled hazard ratios [95% confidence intervals] across Medicare and CPRD: 0.81 [0.75-0.88] in Analysis 1, 0.98 [0.92-1.06] in Analysis 2, 0.83 [0.75-0.91] in Analysis 3, 0.75 [0.65-0.85] in Analysis 4). Amiloride vs. triamterene, although less precise, also suggested a potential reduction in risk in 3 out of 4 analyses (0.86 [0.66-1.11] in Analysis 1, 0.98 [0.79-1.23] in Analysis 2, 0.74 [0.54-1.00] in Analysis 3, 0.61 [0.36-1.05] in Analysis 4). Other analyses suggested likely no major differences in risk (probenecid, salbutamol, montelukast, propranolol/carvedilol, and anastrozole) or had limited precision precluding a definitive conclusion (semaglutide, ciloztozol, levetiracetam). Future replication studies should be considered to validate our findings.

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引用次数: 0
A Systematic Review of the Costs of Drug-Associated Acute Kidney Injury and Potential Cost Savings With Nephrotoxin Stewardship Prevention Strategies. 药物相关急性肾损伤的成本及肾毒素管理预防策略的潜在成本节约系统回顾。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-04-01 Epub Date: 2024-11-13 DOI: 10.1002/cpt.3493
Britney A Stottlemyer, Tiffany Tran, Kangho Suh, Sandra L Kane-Gill

There is a scarcity of information related to the financial impact of acute kidney injury (AKI), and even more so the economics of drug-associated AKI (D-AKI). Our goal was to provide a comprehensive summary of the economic burden of D-AKI by evaluating the costs of D-AKI compared to not developing AKI and cost savings associated with nephrotoxin stewardship approaches. Following the PRISMA guidelines, a literature search was conducted using PubMed to identify articles from database inception through November 2023. The main outcomes included AKI incidence, resource use, and cost of nephrotoxin stewardship programs/D-AKI event or no event. Key findings were summarized based on whether the study compared the cost of D-AKI vs. no AKI or identified potential cost savings associated with a nephrotoxin stewardship method to prevent D-AKI or worsening D-AKI. All costs were adjusted to USD2023. Twenty-five studies met the inclusion criteria. Eight studies compared the cost of D-AKI to no AKI. Total admission costs of patients who developed D-AKI ranged from $47,696 to $173,569. Nineteen studies implemented nephrotoxin stewardship with 12 substituting a less nephrotoxic drug; five using therapeutic drug monitoring and two altering drug dosing to limit exposure. Overall, these prevention strategies ranged from $5,171 to $364,973 in total medical cost savings and $17 to $942 in total cost savings per patient-day. The in-hospital economic impact of D-AKI is substantial. Implementing nephrotoxin stewardship strategies to reduce D-AKI is associated with cost savings. Institutions should adopt strategic and efficient nephrotoxin stewardship programs to optimize patient care and reduce costs.

与急性肾损伤(AKI)的经济影响相关的信息很少,而与药物相关的急性肾损伤(D-AKI)的经济影响相关的信息则更少。我们的目标是全面总结 D-AKI 的经济负担,评估 D-AKI 与未发生 AKI 相比的成本,以及与肾毒性药物管理方法相关的成本节约。按照 PRISMA 指南,我们使用 PubMed 进行了文献检索,以确定从数据库建立之初到 2023 年 11 月期间的文章。主要结果包括 AKI 发生率、资源使用情况以及肾毒性药物管理计划/D-AKI 事件或无事件的成本。根据研究是否比较了D-AKI与未发生AKI的成本,或确定了与肾毒素管理方法相关的潜在成本节约,以预防D-AKI或D-AKI恶化,对主要研究结果进行了总结。所有成本均调整为 2023 美元。25 项研究符合纳入标准。八项研究比较了 D-AKI 与无 AKI 的成本。发生 D-AKI 的患者入院总费用从 47,696 美元到 173,569 美元不等。19 项研究实施了肾毒性药物管理,其中 12 项研究使用了肾毒性较低的药物替代品;5 项研究使用了治疗药物监测,2 项研究改变了药物剂量以限制药物暴露。总体而言,这些预防策略节省的医疗总成本从 5,171 美元到 364,973 美元不等,每个患者日节省的总成本从 17 美元到 942 美元不等。D-AKI 对院内经济的影响是巨大的。实施肾毒性药物管理策略以减少 D-AKI 与成本节约相关。医疗机构应采取战略性和高效的肾毒性药物管理计划,以优化患者护理并降低成本。
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引用次数: 0
Duration of Time Intervals for Risk Minimization Measure Effectiveness Studies.
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-04-01 Epub Date: 2025-01-24 DOI: 10.1002/cpt.3569
Sharon C M Essink, Inge M Zomerdijk, Thomas Goedecke, Sabine M J M Straus, Helga Gardarsdottir, Marie L De Bruin

Insights into the time needed for evaluation of risk minimization measures' (RMMs) effectiveness might identify areas for improvement. We assessed the duration of time intervals between regulatory milestones for RMM effectiveness studies assessed by the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA). We included completed RMM effectiveness post-authorization safety studies (PASSs) assessed by PRAC between 2016 and 2022. Regulatory documents submitted by marketing authorization holders and assessment reports were extracted from non-public EMA databases. To calculate the duration of time intervals, we collected the dates of study request, protocol assessment start, protocol approval, study start, final study report assessment start, and final study report PRAC outcome. We identified 98 PASSs. The median duration from study request to final study report PRAC outcome was 52 months (Q1-Q3: 40-70). The median duration from study request to study start was 21 months (Q1-Q3: 15-30; n = 95) and from study start to final study report assessment start was 21 months (Q1-Q3: 13-36; n = 95). The final study report assessment often comprised <6 months (median: 4; Q1-Q3: 1-6). For PASSs with a PRAC-approved protocol (n = 80, 81.6%), the median duration of protocol assessment was 7 months (Q1-Q3: 4-10). Concluding, the median duration from study request to RMM effectiveness PASS completion exceeded 4 years. Next to the study conduct duration, the period from study request until study start was the most time-consuming. The duration of this period might be minimized by improved guidance on RMM effectiveness PASSs and encouraging timely protocol submission.

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引用次数: 0
Contemporary Use of β-Blockers in Heart Failure Patients With and Without Atrial Fibrillation: A Nationwide Database Analysis. 有心房颤动和无心房颤动的心力衰竭患者目前使用β-受体阻滞剂的情况:全国数据库分析。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-04-01 Epub Date: 2024-11-18 DOI: 10.1002/cpt.3496
Michikazu Nakai, Yoshitaka Iwanaga, Koshiro Kanaoka, Yoko Sumita, Yuichi Nishioka, Tomoya Myojin, Katsuki Okada, Tatsuya Noda, Tomoaki Imamura, Yoshihiro Miyamoto

Evidence of the effectiveness of β-blockers in heart failure (HF) and atrial fibrillation (AF) in a contemporary cohort is controversial. This study investigated the association between the use of β-blockers and prognosis in hospitalized HF patients with and without AF in Japan. Patients hospitalized with the first episode of acute HF were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between April 2014 and March 2021. Associations of β-blocker use and prognosis were compared by propensity score matching among the AF or non-AF group. A mixed-effects survival model was used, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Among 428,650 patients discharged with HF in 4,433 hospitals, 175,174 (40.9%) were ≥ 85 years old, 151,873 (35.4%) had complicated AF, and 236,457 (55.2%) were β-blocker users. In a matched AF group, β-blocker use was associated with a lower composite outcome of all-cause mortality or HF rehospitalization (HR [95% CI], 0.95 [0.93-0.97]). A similar result was obtained in a matched non-AF group (0.95 [0.94-0.96]). In addition, the HRs in patients aged ≥ 85 years and female patients were 1.00 [0.98-1.02] and 1.01 [0.98-1.03] in the AF group and 1.03 [1.01-1.05] and 0.98 [0.97-1.00] in the non-AF group, respectively. The favorable prognostic associations of β-blocker use were observed regardless of AF in patients across a broad spectrum of HF in a superaged society.

在当代人群中,β-受体阻滞剂对心力衰竭(HF)和心房颤动(AF)的有效性证据尚存在争议。本研究调查了日本有房颤和无房颤的住院高血压患者使用β-受体阻滞剂与预后之间的关系。研究人员从2014年4月至2021年3月期间的日本全国健康保险索赔和特定健康检查数据库中找到了首次急性心房颤动住院患者。通过倾向得分匹配法比较了心房颤动组和非心房颤动组患者使用β受体阻滞剂与预后的关系。研究采用了混合效应生存模型,并计算了危险比 (HR) 和 95% 置信区间 (CI)。在 4,433 家医院的 428,650 名因心房颤动出院的患者中,175,174 人(40.9%)年龄≥ 85 岁,151,873 人(35.4%)患有复杂性心房颤动,236,457 人(55.2%)使用过 β 受体阻滞剂。在匹配的心房颤动组中,β-受体阻滞剂的使用与较低的全因死亡率或高血压再住院综合结果相关(HR [95%CI],0.95 [0.93-0.97])。在匹配的非房颤组中也得到了类似的结果(0.95 [0.94-0.96])。此外,心房颤动组中年龄≥ 85 岁的患者和女性患者的 HR 分别为 1.00 [0.98-1.02] 和 1.01 [0.98-1.03],非心房颤动组中的 HR 分别为 1.03 [1.01-1.05] 和 0.98 [0.97-1.00]。在一个超高龄社会中,无论房颤与否,使用β受体阻滞剂都能为各种类型的心房颤动患者带来有利的预后。
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引用次数: 0
Discovering Severe Adverse Reactions From Pharmacokinetic Drug-Drug Interactions Through Literature Analysis and Electronic Health Record Verification. 通过文献分析和电子病历验证,从药代动力学药物相互作用中发现严重不良反应。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-04-01 Epub Date: 2024-11-25 DOI: 10.1002/cpt.3500
Eugene Jeong, Yu Su, Lang Li, You Chen

While drug-drug interactions (DDIs) and their pharmacokinetic (PK) mechanisms are well-studied prior to drug approval, severe adverse drug reactions (SADRs) caused by DDIs often remain underrecognized due to limitations in pre-marketing clinical trials. To address this gap, our study utilized a literature database, applied natural language processing (NLP) techniques, and conducted multi-source electronic health record (EHR) validation to uncover underrecognized DDI-SADR signals that warrant further investigation. PubMed abstracts related to DDIs from January 1962 to December 2023 were retrieved. We utilized PubTator Central for Named Entity Recognition (NER) to identify drugs and SADRs and employed SciFive for Relation Extraction (RE) to extract DDI-SADR signals. The extracted signals were cross-referenced with the DrugBank database and validated using logistic regression, considering risk factors including patient demographics, drug usage, and comorbidities, based on EHRs from Vanderbilt University Medical Center (VUMC) and the All of Us research program. From 160,321 abstracts, we identified 111 DDI-SADR signals. Seventeen were statistically significant (13 by one EHR and 4 by both EHR databases), with 9 being previously not recorded in the DrugBank. These included methadone-ciprofloxacin-respiratory depression, oxycodone-fluvoxamine-clonus, tramadol-fluconazole-hallucination, simvastatin-fluconazole-rhabdomyolysis, ibrutinib-amiodarone-atrial fibrillation, fentanyl-diltiazem-delirium, clarithromycin-voriconazole-acute kidney injury, colchicine-cyclosporine-rhabdomyolysis, and methadone-voriconazole-arrhythmia (odds ratios (ORs) ranged from 1.9 to 35.83, with P-values ranging from < 0.001 to 0.017). Utilizing NLP to extract DDI-SADRs from Biomedical Literature and validating these findings through multiple-source EHRs represents a pioneering approach in pharmacovigilance. This method uncovers clinically relevant SADRs resulting from DDIs that were not evident in pre-marketing trials or the existing DDI knowledge base.

虽然在药物批准前对药物相互作用(DDI)及其药代动力学(PK)机制进行了充分研究,但由于上市前临床试验的局限性,DDI 引起的严重药物不良反应(SADR)往往仍未得到充分认识。为了填补这一空白,我们的研究利用文献数据库,应用自然语言处理(NLP)技术,并进行了多源电子病历(EHR)验证,以发现未被充分认识的、值得进一步研究的DDI-SADR信号。我们检索了 1962 年 1 月至 2023 年 12 月期间与 DDI 相关的 PubMed 摘要。我们利用 PubTator Central 的命名实体识别(NER)来识别药物和 SADR,并利用 SciFive 的关系提取(RE)来提取 DDI-SADR 信号。根据范德堡大学医学中心(VUMC)和 "我们所有人 "研究项目的电子病历,将提取的信号与 DrugBank 数据库进行交叉比对,并使用逻辑回归进行验证,其中考虑了包括患者人口统计学特征、药物使用情况和合并症在内的风险因素。从 160,321 份摘要中,我们发现了 111 个 DDI-SADR 信号。其中 17 个具有统计学意义(一个电子病历数据库发现 13 个,两个电子病历数据库发现 4 个),9 个以前未在药物库中记录。其中包括美沙酮-环丙沙星-呼吸抑制、羟考酮-氟伏沙明-阵挛、曲马多-氟康唑-幻觉、辛伐他汀-氟康唑-横纹肌溶解、伊布替尼-胺碘酮-心房颤动、芬太尼-地尔硫卓-谵妄、克拉霉素-伏立康唑-急性肾损伤、秋水仙碱-环孢素-横纹肌溶解,以及美沙酮-伏立康唑-心律失常(几率比(ORs)从 1.9至35.83,P值从
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引用次数: 0
Return of Clinically Actionable Pharmacogenetic Results From Molecular Tumor Board DNA Sequencing Data: Workflow and Estimated Costs. 从分子肿瘤委员会DNA测序数据中返回临床可操作的药物遗传学结果:工作流程和估计成本。
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-04-01 Epub Date: 2025-01-09 DOI: 10.1002/cpt.3545
Hyunwoo Koo, Tayler B Smith, John T Callaghan, Wilberforce Osei, Steven M Bray, Emma M Tillman, Mya T Tran, Christopher A Fausel, Bryan P Schneider, Tyler Shugg, Todd C Skaar

Pharmacogenetic testing can prevent severe toxicities from several oncology drug therapies; it also has the potential to improve the outcomes from supportive care drugs. Paired tumor and germline sequencing is increasingly common in oncology practice; these include sequencing of pharmacogenes, but the germline pharmacogenetic variants are rarely included in the clinical reports, despite many being clinically actionable. We established an informatics workflow to evaluate the clinical sequencing results for pharmacogenetic variants. We used the Aldy computational tool, which we have previously shown to determine the variant alleles in 14 pharmacogenes in clinical sequencing data with >99% accuracy, to identify pharmacogenetic variants in the clinical whole exome sequencing from our molecular tumor board. Patients with genetic variants that are clinically actionable for their individual therapy programs, including both treatment and supportive care, are referred to a clinical pharmacogenetics testing laboratory for confirmation. Through an evaluation of our weekly informatics workflow, we determined it took approximately 3.25 hours to complete the analysis of the sequencing data from approximately 20 patients. Using a United States pharmacist's median salary, we estimated the incremental added cost of the process to be only ~$15 per patient. This adds only a minor increase to the patient's cost of testing and has the potential to improve the safety and efficacy of their treatment.

药物遗传学检测可以预防一些肿瘤药物治疗产生的严重毒性;它也有可能改善支持性护理药物的效果。配对肿瘤和生殖系测序在肿瘤学实践中越来越普遍;这些包括药物基因的测序,但生殖系药物遗传变异很少包括在临床报告中,尽管许多是临床可操作的。我们建立了信息学工作流程来评估药物遗传变异的临床测序结果。我们使用Aldy计算工具(我们之前已经证明该工具可以在临床测序数据中确定14个药物基因的变异等位基因,准确率为bbbb99 %)来识别来自我们分子肿瘤板的临床全外显子组测序中的药物遗传变异。具有基因变异的患者,如果其个体治疗方案在临床上可行,包括治疗和支持性护理,则应转介到临床药物遗传学检测实验室进行确认。通过对每周信息学工作流程的评估,我们确定完成对大约20名患者的测序数据的分析大约需要3.25小时。使用美国药剂师的中位数工资,我们估计该过程的增量增加成本仅为每位患者约15美元。这只会轻微增加患者的检测费用,并有可能提高治疗的安全性和有效性。
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引用次数: 0
Chat GPT vs. Clinical Decision Support Systems in the Analysis of Drug-Drug Interactions.
IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-04-01 Epub Date: 2025-02-11 DOI: 10.1002/cpt.3585
Thorsten Bischof, Valentin Al Jalali, Markus Zeitlinger, Anselm Jorda, Michelle Hana, Karla-Nikita Singeorzan, Nikolaus Riesenhuber, Gunar Stemer, Christian Schoergenhofer

The current standard method for the analysis of potential drug-drug interactions (pDDIs) is time-consuming and includes the use of multiple clinical decision support systems (CDSSs) and the interpretation by healthcare professionals. With the emergence of large language models developed with artificial intelligence, an interesting alternative arose. This retrospective study included 30 patients with polypharmacy, who underwent a pDDI analysis between October 2022 and August 2023, and compared the performance of Chat GPT and established CDSSs (MediQ®, Lexicomp®, Micromedex®) in the analysis of pDDIs. A multidisciplinary team interpreted the obtained results and decided upon clinical relevance and assigned severity grades using three categories: (i) contraindicated, (ii) severe, (iii) moderate. The expert review identified a total of 280 clinically relevant pDDIs (3 contraindications, 13 severe, 264 moderate) using established CDSSs, compared with 80 pDDIs (2 contraindications, 5 severe, 73 moderate) using Chat GPT. Chat GPT almost entirely neglected pDDIs with the risk to QTc prolongation (85 vs. 8), which could also not be sufficiently improved by using a specific prompt. To assess the consistency of the results provided by Chat GPT, we repeated each query and found inconsistent results in 90% of the cases. In contrast, Chat GPT provided acceptable and comprehensible recommendations for specific questions on side effects. The use of Chat GPT for the identification of pDDIs cannot be recommended currently, because clinically relevant pDDIs were not detected, there were obvious errors and results were inconsistent. However, if these limitations are addressed accordingly, it is a promising platform for the future.

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