How healthy are the "Healthy volunteers"? Penetrance of NAFLD in the biomedical research volunteer pool.
How healthy are the "Healthy volunteers"? Penetrance of NAFLD in the biomedical research volunteer pool.
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“健康志愿者”的健康状况如何？ NAFLD在生物医学研究志愿者池中的渗透率。
DOI：
10.1002/hep.29247
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Rotman Y
中科院分区：
文献类型：
--
作者：
Takyar V;Nath A;Beri A;Gharib AM;Rotman Y
健康的志愿者对生物医学研究至关重要。意外纳入非酒精性脂肪性肝病（NAFLD）受试者作为对照可能会影响研究有效性和受试者安全性。鉴于NAFLD在普通人群中的患病率不断上升，我们试图确定其在临床试验志愿者中的患病率和潜在影响。在2011-2015年间诊断为“健康志愿者”且无已知肝病的受试者中开展的横断面研究。受试者被定义为假定NAFLD（pNF，女性ALT≥20或男性ALT ≥31且BMI>25）、健康非NAFLD对照（HC，正常ALT和BMI）或不确定。3160例受试者作为健康志愿者参加了149项临床试验（每例受试者1-29项试验）。1732例（55%）BMI > 25 kg/m2，1382例（44%）ALT异常。881例受试者（27.9%）存在pNF，这些受试者年龄大于HC，甘油三酯、LDL-C和HbA 1c较高，HDL-C较低（所有受试者p<0.001）。这149项试验包括101项非干预性试验、33项干预性试验和15项疫苗试验。在10、41和98项试验中，分别估计招募NAFLD受试者作为对照对研究有效性的影响为可能、很可能和不太可能。pNF受试者的比例（28-29%）在影响方面没有差异。只有14%的试验同时使用BMI和ALT进行筛查。筛选的ALT临界值基于当地参考值。研究期间3-4级ALT升高罕见，但在pNF受试者中比HC受试者更常见（4 vs. 1）。NAFLD在临床试验志愿者中很常见，而且经常被忽视，尽管它对受试者的安全性和研究结果的有效性有潜在影响。提高对NAFLD患病率的认识和更严格的ALT临界值可能会改善这一问题。
Healthy volunteers are crucial for biomedical research. Inadvertent inclusion of subjects with non-alcoholic fatty liver disease (NAFLD) as controls can compromise study validity and subject safety. Given the rising prevalence of NAFLD in the general population, we sought to identify its prevalence and potential impact in volunteers for clinical trials. Cross-sectional study of subjects with “Healthy Volunteer” diagnosis between 2011-2015 and no known liver disease. Subjects were defined presumed NAFLD (pNF, ALT≥20 for women or ≥31 for men and BMI>25), healthy non-NAFLD controls (HC, normal ALT and BMI), or indeterminate. 3160 subjects participated as healthy volunteers in 149 clinical trials, (1-29 trials per subject). 1732 (55%) had BMI > 25 kg/m2 and 1382 (44%) had abnormal ALT. pNF was present in 881 subjects (27.9%) and these subjects were older than HC, and had higher triglycerides, LDL-C, and HbA1c and lower HDL-C (p<0.001 for all) . The 149 trials included 101 non-interventional, 33 interventional and 15 vaccine trials. The impact on study validity of recruiting NAFLD subjects as controls was estimated as likely, probable and unlikely in 10, 41 and 98 trials, respectively. The proportion of pNF subjects (28-29%) did not differ by impact. Only 14% of trials used both BMI and ALT for screening. ALT cut-offs for screening were based on local reference values. Grade 3-4 ALT elevations during the study period were rare but more common in pNF subjects than HC (4 vs. 1). NAFLD is common and often overlooked in volunteers for clinical trials, despite its potential impact on subject safety and validity of study findings. Increased awareness of NAFLD prevalence and stricter ALT cut-offs may ameliorate this problem.
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DOI：
10.1016/j.nutres.2014.10.007
发表时间：
2014-12
期刊：
Nutrition research (New York, N.Y.)
影响因子：
--
作者：
Courville AB;DiVito M;Moyer L;Rossinoff A;Royster C;Psota T;Ayres E;Zambell KL
通讯作者：
Zambell KL
影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH
影响因子：
4.3
作者：
Canet MJ;Cherrington NJ
通讯作者：
Cherrington NJ
影响因子：
4.1
作者：
Chan, Wah-Kheong;Tan, Alexander Tong-Boon;Goh, Khean-Lee
通讯作者：
Goh, Khean-Lee
影响因子：
13.5
作者：
Dutta, Anand;Saha, Chandan;Chalasani, Naga
通讯作者：
Chalasani, Naga