High-Throughput Computing to Automate Population-Based Studies to Detect the 30-Day Risk of Adverse Outcomes After New Outpatient Medication Use in Older Adults with Chronic Kidney Disease: A Clinical Research Protocol.
High-Throughput Computing to Automate Population-Based Studies to Detect the 30-Day Risk of Adverse Outcomes After New Outpatient Medication Use in Older Adults with Chronic Kidney Disease: A Clinical Research Protocol.
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DOI：
10.1177/20543581231221891
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发表时间：
2024
影响因子：
1.7
通讯作者：
Garg, Amit X.
中科院分区：
文献类型：
--
作者：
Abdullah, Sheikh S.;Rostamzadeh, Neda;Muanda, Flory T.;McArthur, Eric;Weir, Matthew A.;Sontrop, Jessica M.;Kim, Richard B.;Kamran, Sedig;Garg, Amit X.
关键词：
在监管机构批准后的几年内，约三分之一的处方药被发现存在安全问题。老年人，尤其是患有慢性肾病的老年人，特别容易遭受处方药不良反应的风险。该协议描述了一种新方法，可以使用行政医疗保健数据更有效地识别可靠的药物安全信号。使用高通量计算和自动化对加拿大安大略省的老年人进行 700 多项药物安全队列研究。每项研究将比较开始使用新处方药的患者（新使用者）与一组具有相似基线健康特征的非使用者的 74 项急性（30 天）结果。将在基线肾功能的各个层次内评估风险。这些研究将是基于人群的新用户队列研究，使用加拿大安大略省的关联行政医疗保健数据库（2008年1月1日至2020年3月1日）进行。这些研究的来源人群将是年龄在 66 岁或以上的安大略省居民，他们在研究期间通过安大略省药物福利 (ODB) 计划至少配了一份门诊处方（所有居民都享有全民医疗保健，65 岁以上的居民通过 ODB 享有全民处方药保险）。在研究期间，我们在源人群中确定了 320 万老年人，并建立了 700 多个初始药物队列，每个队列都包含相互排斥的新使用者和非使用者群体。非用户被随机分配队列进入日期，其处方开始日期的分布与新用户相同。资格标准包括入组日期前 12 个月内的基线估计肾小球滤过率 (eGFR) 测量（新用户组入组前的中位时间为 71 天）、之前没有接受过维持性透析或肾移植，以及之前没有与研究药物属于同一子类的药物处方。新使用者和非使用者将在基线 eGFR 的 3 层内使用倾向评分的治疗加权逆概率在约 400 个基线健康特征上进行平衡：≥60、45 至 <60、<45 mL/min 每 1.73 m2。我们将在进入队列后 30 天内比较新用户组和非用户组的 74 项临床相关结果（17 项综合结果和 57 项单独结果）。我们使用预先指定的方法来确定这 74 种结果。在每个队列中，我们将分别使用修正泊松回归和二项式回归获得 eGFR 层特定加权风险比和风险差异。将检查 eGFR 类别的加法和乘法相互作用。满足预先指定标准（识别信号）的药物结果关联将在额外分析（包括生存、阴性对照暴露和 E 值分析）和可视化中进一步检查。初始药物队列的新用户中位数为 6120 名（四分位数范围：1469-38 839），非用户中位数为 1 088 301 名（四分位间距：751 697-1 267 009）。新使用者数量最多的药物是阿莫西林三水合物（n = 1 000 032）、头孢氨苄（n = 571 566）、处方对乙酰氨基酚（n = 571 563）和环丙沙星（n = 504,374）；这些群组中 19% 至 29% 的新用户的 eGFR <60 mL/min 每 1.73 m2。尽管我们使用稳健的技术来平衡基线指标并通过指示来控制混杂，但残留混杂仍然是可能的。仅检查急性（30 天）结果。我们的数据来源不包括非处方（非处方）药物或医院处方药物，也不包括 65 岁以下儿童或成人的门诊处方药使用情况。这种加速进行上市后药物安全研究的方法有可能更有效地检测弱势群体的药物安全信号。该方案的结果可能最终有助于提高用药安全性。
Safety issues are detected in about one third of prescription drugs in the years following regulatory agency approval. Older adults, especially those with chronic kidney disease, are at particular risk of adverse reactions to prescription drugs. This protocol describes a new approach that may identify credible drug-safety signals more efficiently using administrative health care data. To use high-throughput computing and automation to conduct 700+ drug-safety cohort studies in older adults in Ontario, Canada. Each study will compare 74 acute (30-day) outcomes in patients who start a new prescription drug (new users) to a group of nonusers with similar baseline health characteristics. Risks will be assessed within strata of baseline kidney function. The studies will be population-based, new-user cohort studies conducted using linked administrative health care databases in Ontario, Canada (January 1, 2008, to March 1, 2020). The source population for these studies will be residents of Ontario aged 66 years or older who filled at least one outpatient prescription through the Ontario Drug Benefit (ODB) program during the study period (all residents have universal health care, and those aged 65+ have universal prescription drug coverage through the ODB). We identified 3.2 million older adults in the source population during the study period and built 700+ initial medication cohorts, each containing mutually exclusive groups of new users and nonusers. Nonusers were randomly assigned cohort entry dates that followed the same distribution of prescription start dates as new users. Eligibility criteria included a baseline estimated glomerular filtration rate (eGFR) measurement within 12 months before the cohort entry date (median time was 71 days before cohort entry in the new user group), no prior receipt of maintenance dialysis or a kidney transplant, and no prior prescriptions for drugs in the same subclass as the study drug. New users and nonusers will be balanced on ~400 baseline health characteristics using inverse probability of treatment weighting on propensity scores within 3 strata of baseline eGFR: ≥60, 45 to <60, <45 mL/min per 1.73 m2. We will compare new user and nonuser groups on 74 clinically relevant outcomes (17 composites and 57 individual outcomes) in the 30 days after cohort entry. We used a prespecified approach to identify these 74 outcomes. In each cohort, we will obtain eGFR-stratum-specific weighted risk ratios and risk differences using modified Poisson regression and binomial regression, respectively. Additive and multiplicative interaction by eGFR category will be examined. Drug-outcome associations that meet prespecified criteria (identified signals) will be further examined in additional analyses (including survival, negative-control exposure, and E-value analyses) and visualizations. The initial medication cohorts had a median of 6120 new users per cohort (interquartile range: 1469-38 839) and a median of 1 088 301 nonusers (interquartile range: 751 697-1 267 009). Medications with the largest number of new users were amoxicillin trihydrate (n = 1 000 032), cephalexin (n = 571 566), prescription acetaminophen (n = 571 563), and ciprofloxacin (n = 504,374); 19% to 29% of new users in these cohorts had an eGFR <60 mL/min per 1.73 m2. Despite our use of robust techniques to balance baseline indicators and to control for confounding by indication, residual confounding will remain a possibility. Only acute (30-day) outcomes will be examined. Our data sources do not include nonprescription (over-the-counter) drugs or drugs prescribed in hospitals and do not include outpatient prescription drug use in children or adults <65 years. This accelerated approach to conducting postmarket drug-safety studies has the potential to more efficiently detect drug-safety signals in a vulnerable population. The results of this protocol may ultimately help improve medication safety.
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影响因子：
3.2
作者：
Abdi, Herve;Williams, Lynne J.
通讯作者：
Williams, Lynne J.
影响因子：
2
作者：
Austin PC
通讯作者：
Austin PC
影响因子：
3.7
作者：
Fleet, Jamie L.;Dixon, Stephanie N.;Garg, Amit X.
通讯作者：
Garg, Amit X.
影响因子：
6.7
作者：
Eichler HG;Bloechl-Daum B;Broich K;Kyrle PA;Oderkirk J;Rasi G;Santos Ivo R;Schuurman A;Senderovitz T;Slawomirski L;Wenzl M;Paris V
通讯作者：
Paris V
DOI：
10.1161/circoutcomes.113.000359
发表时间：
2013-09-01
期刊：
Circulation. Cardiovascular quality and outcomes
影响因子：
--
作者：
Brookhart MA;Wyss R;Layton JB;Stürmer T
通讯作者：
Stürmer T