Johnson Lorraine, Shapiro Mira, Needell Deanna, Stricker Raphael B
LymeDisease.org, Los Angeles, CA 91040, USA.
Analytic Designers LLC, Bethesda, MD 20817, USA.
Healthcare (Basel). 2024 Dec 25;13(1):20. doi: 10.3390/healthcare13010020.
BACKGROUND/OBJECTIVES: Although eligibility criteria for clinical trials significantly impact study outcomes, these criteria are often established without scientific justification, leading to delayed recruitment, small sample sizes, and limited study generalizability. Persistent Lyme disease (PLD) presents unique challenges due to symptom variability, inconsistent treatment responses, and the lack of reliable biomarkers, underscoring the need for scientifically justified eligibility criteria.
This study examines the effects of commonly used enrollment criteria on sample yield in PLD clinical trials using real-world data (RWD) from the MyLymeData patient registry. The study also compares the effects of these criteria on enrollment for PLD versus acute Lyme disease (ALD) trials and evaluates the scientific rationale for each criterion.
Data from 4183 Lyme disease patients enrolled in the MyLymeData registry were analyzed to assess the prevalence and cumulative impact of various criteria on sample yield. A comparative analysis of cohorts with PLD (n = 3589) versus ALD (n = 594) was conducted to identify differences in sample attrition.
In a large PLD cohort study, we found that current commonly used eligibility criteria would exclude approximately 90% of patients, significantly limiting study generalizability. Substantial differences in sample attrition between PLD and ALD cohorts highlight the need for tailored criteria. The strength of scientific justification varied widely among criteria.
This study demonstrates the importance of using RWD to optimize eligibility criteria in PLD clinical trials. By providing insights into the balance between sample attrition and scientific justification, researchers can enhance trial feasibility, generalizability, and robustness. Our RWD sample demonstrates that researchers could substantially increase the sample yield from 10% to 64% by loosening restrictions on coinfections and misdiagnoses of chronic fatigue syndrome, fibromyalgia syndrome, and psychiatric conditions.
背景/目的：尽管临床试验的纳入标准对研究结果有重大影响，但这些标准的制定往往缺乏科学依据，导致招募延迟、样本量小以及研究的可推广性受限。持续性莱姆病（PLD）由于症状多变、治疗反应不一致以及缺乏可靠的生物标志物而带来了独特的挑战，这凸显了制定具有科学依据的纳入标准的必要性。
本研究利用来自MyLymeData患者登记处的真实世界数据（RWD），考察常用纳入标准对PLD临床试验样本量的影响。该研究还比较了这些标准对PLD与急性莱姆病（ALD）试验招募的影响，并评估了每个标准的科学依据。
对MyLymeData登记处登记的4183例莱姆病患者的数据进行分析，以评估各种标准对样本量的患病率和累积影响。对PLD队列（n = 3589）和ALD队列（n = 594）进行比较分析，以确定样本损耗的差异。
在一项大型PLD队列研究中，我们发现当前常用的纳入标准将排除约90%的患者，显著限制了研究的可推广性。PLD和ALD队列之间样本损耗的显著差异凸显了制定针对性标准的必要性。各标准的科学依据强度差异很大。
本研究证明了使用RWD优化PLD临床试验纳入标准的重要性。通过深入了解样本损耗与科学依据之间的平衡，研究人员可以提高试验的可行性、可推广性和稳健性。我们的RWD样本表明，研究人员可以通过放宽对合并感染以及慢性疲劳综合征、纤维肌痛综合征和精神疾病误诊的限制，将样本量从10%大幅提高到64%。
