Evaluating ADHD medication trial representativeness: a Swedish population-based study comparing hypothetically trial-eligible and trial-ineligible individuals

IF 30.8 1区医学 Q1 PSYCHIATRY

Lancet Psychiatry Pub Date : 2025-01-06 DOI:10.1016/s2215-0366(24)00396-1

Miguel Garcia-Argibay, Zheng Chang, Isabell Brikell, Ralf Kuja-Halkola, Brian M D'Onofrio, Paul Lichtenstein, Jeffrey H Newcorn, Stephen V Faraone, Henrik Larsson, Samuele Cortese

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引用次数: 0

Abstract

Background

Randomised controlled trials (RCTs) evaluating ADHD medications often use strict eligibility criteria, potentially limiting generalisability to patients in real-world clinical settings. We aimed to identify the proportion of individuals with ADHD who would be ineligible for medication RCTs and evaluate differences in treatment patterns and clinical and functional outcomes between RCT-eligible and RCT-ineligible individuals.

Methods

We used multiple Swedish national registries to identify individuals with ADHD, aged at least 4 years at the age of diagnosis, initiating pharmacological treatment between Jan 1, 2007, and Dec 31, 2019, with follow-up up to Dec 31, 2020. Hypothetical RCT ineligibility was established using exclusion criteria from the international MED-ADHD dataset, including 164 RCTs of ADHD medications. Cox models evaluated differences in medication switching and discontinuation within 1 year between eligible and ineligible individuals. Quasi-Poisson models compared eligible and ineligible individuals on rates of psychiatric hospitalisations, injuries or accidents, and substance use disorder within 1 year of initiating ADHD medications. People with lived experience of ADHD were not involved in the research and writing process.

Findings

Of 189 699 individuals included in the study cohort (112 153 men and boys [59%] and 77 546 women and girls [41%]; mean age 21·52 years [SD 12·83; range 4–68]) initiating ADHD medication, 53% (76 477 [74%] of 103 023 adults [aged >17 years], 12 658 [35%] of 35 681 adolescents [aged 13–17 years], and 10 643 [21%] of 50 995 children [aged <13 years]) would have been ineligible for RCT participation. Ethnicity data were not available. Ineligible individuals had a higher likelihood of treatment switching (hazard ratio 1·14, 95% CI 1·12–1·16) and a decreased likelihood of medication discontinuation (0·96, 0·94–0·98) compared with eligible individuals. Individuals ineligible for RCTs had significantly higher rates of psychiatric hospitalisations (ncidence rate ratio 9·68, 95% CI 9·57–9·78) and specialist care visits related to substance use disorder (14·78, 14·64–14·91), depression (6·00, 5·94–6·06), and anxiety (11·63, 11·56–11·69).

Interpretation

Individuals ineligible for ADHD medication trials face higher risks of adverse outcomes. This study provides the first empirical evidence for the limited generalisability of ADHD RCTs to real-world clinical populations, by applying eligibility criteria extracted from a comprehensive dataset of RCTs to a large real-world cohort. Triangulating evidence from RCTs and real-world studies is crucial to inform rigorous evidence-based treatment guidelines.

Funding

National Institute of Healthcare and Research, European Union's Horizon 2020, and Swedish Research Council.

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评估ADHD药物试验的代表性：一项瑞典基于人群的研究，比较假设符合试验条件和不符合试验条件的个体

评估ADHD药物的随机对照试验（RCTs）通常使用严格的资格标准，潜在地限制了对现实世界临床环境中患者的推广。我们的目的是确定不符合药物随机对照试验的ADHD个体的比例，并评估符合和不符合随机对照试验的个体在治疗模式、临床和功能结局方面的差异。方法：我们使用多个瑞典国家登记处来识别ADHD患者，这些患者在诊断时年龄至少为4岁，在2007年1月1日至2019年12月31日期间开始药物治疗，随访至2020年12月31日。使用国际MED-ADHD数据集的排除标准，包括164项ADHD药物的RCT，建立假设的RCT不合格。Cox模型评估了符合条件和不符合条件的个体在1年内药物转换和停药的差异。准泊松模型比较了符合条件和不符合条件的个体在开始ADHD药物治疗一年内的精神住院率、伤害或事故率和物质使用障碍率。有过ADHD生活经历的人没有参与研究和写作过程。纳入研究队列的189 699人（112 153名男性和男孩[59%]和77 546名女性和女孩[41%]）；平均年龄21.52岁[SD 12.83；（范围4-68）),53%（103023名成人[17岁]中的76477名[74%]，35681名青少年[13 - 17岁]中的12658名[35%]，50995名儿童[13岁]中的10643名[21%]）不符合参加随机对照试验的条件。没有种族数据。与符合条件的个体相比，不符合条件的个体转换治疗的可能性更高（风险比1.14,95% CI 1.12 - 1.16），停药的可能性更低（0.96,0.94 - 0.98）。不符合rct条件的个体精神科住院率（发病率比为9.68,95% CI为9.57 - 9.78）和与物质使用障碍（14.78、14.64 - 14.91）、抑郁症（6.00、5.94 - 4.06）和焦虑症（11.63、11.56 - 11.69）相关的专科护理就诊率显著较高。解释：不符合ADHD药物试验条件的个体面临更高的不良后果风险。本研究通过将从全面的随机对照试验数据集中提取的资格标准应用于大型现实世界队列，为ADHD随机对照试验在现实世界临床人群中的有限通用性提供了第一个经验证据。对随机对照试验和现实世界研究的证据进行三角测量，对于制定严格的循证治疗指南至关重要。资助：国家卫生保健研究所、欧盟地平线2020和瑞典研究委员会。

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来源期刊

Lancet Psychiatry PSYCHIATRY-

CiteScore

58.30

自引率

0.90%

发文量

期刊介绍： The Lancet Psychiatry is a globally renowned and trusted resource for groundbreaking research in the field of psychiatry. We specialize in publishing original studies that contribute to transforming and shedding light on important aspects of psychiatric practice. Our comprehensive coverage extends to diverse topics including psychopharmacology, psychotherapy, and psychosocial approaches that address psychiatric disorders throughout the lifespan. We aim to channel innovative treatments and examine the biological research that forms the foundation of such advancements. Our journal also explores novel service delivery methods and promotes fresh perspectives on mental illness, emphasizing the significant contributions of social psychiatry.