O'Meara Helen, Carr Daniel F, Evely Jane, Hobbs Mark, McCann Gerard, van Staa Tjeerd, Pirmohamed Munir
Department of Molecular and Clinical Pharmacology, Wolfson Centre for Personalised Medicine, Liverpool, UK.
Br J Clin Pharmacol. 2014 May;77(5):831-8. doi: 10.1111/bcp.12269.
Electronic healthcare records (EHRs) are increasingly used to store clinical information. A secondary benefit of EHRs is their use, in an anonymized form, for observational research. The Clinical Practice Research Datalink (CPRD) contains EHRs from primary care in the UK and, despite 1083 peer-reviewed research publications, has never been used to obtain pharmacogenetic samples. Using a statin-induced myopathy paradigm, we evaluated using the CPRD to obtain patient samples for a pharmacogenetic study targeting 250 cases and 500 controls from UK general practitioner (GP) practices.
The CPRD identified potential patients fitting specific case-definition criteria (active rhabdomyolysis or creatine phosphokinase > four times the upper limit of normal), and corresponding GP practices were asked to invite patient participation. Consenting patients were requested to provide either saliva or blood samples and to complete an ethnicity questionnaire. Control subjects were recruited from the same GP practice (saliva) or a small number of practices (blood). Samples were forwarded for DNA extraction.
Thirty-six months of recruitment yielded DNA samples from 149 statin-induced myopathy cases and 587 tolerant controls. Data show that contacting patients through their GP is a reliable method for obtaining samples without compromising anonymity. Saliva collection directly from patients was considerably less effective than blood sampling. After 10 months of recruitment, saliva sampling was suspended in favour of blood sampling.
We demonstrate the potential of EHRs for identifying accurately phenotyped cases and controls for pharmacogenetic studies. Recruitment was successful only because of the willingness of GP practices to participate and the existence of strong doctor-patient relationships. The present study provides a model that can be implemented in future genetic analyses using EHRs.
电子健康记录（EHRs）越来越多地用于存储临床信息。EHRs的一个次要好处是它们以匿名形式用于观察性研究。临床实践研究数据链（CPRD）包含来自英国初级保健的EHRs，尽管有1083篇经过同行评审的研究出版物，但从未被用于获取药物遗传学样本。我们以他汀类药物引起的肌病为例，评估了利用CPRD从英国全科医生（GP）诊所获取患者样本，以进行针对250例病例和500例对照的药物遗传学研究。
CPRD识别符合特定病例定义标准（活动性横纹肌溶解或肌酸磷酸激酶>正常上限的四倍）的潜在患者，并要求相应的GP诊所邀请患者参与。同意参与的患者被要求提供唾液或血液样本，并填写一份种族问卷。对照受试者从同一GP诊所招募（唾液样本）或少数几个诊所招募（血液样本）。样本被送去进行DNA提取。
36个月的招募工作获得了149例他汀类药物引起的肌病病例和587例耐受对照的DNA样本。数据表明，通过全科医生联系患者是一种可靠的获取样本的方法，同时不会损害匿名性。直接从患者那里收集唾液的效果远不如采集血液样本。招募10个月后，暂停唾液采样，转而采用血液采样。
我们证明了EHRs在为药物遗传学研究准确识别表型明确的病例和对照方面的潜力。招募成功仅仅是因为GP诊所愿意参与以及存在牢固的医患关系。本研究提供了一个可在未来使用EHRs进行基因分析时实施的模型。
