Dunn Adam G, Mandl Kenneth D, Coiera Enrico, Bourgeois Florence T
Centre for Health Informatics, Australian Institute of Health Innovation, University of New South Wales, Sydney, New South Wales, Australia.
Children's Hospital Informatics Program at Harvard-MIT Health Sciences and Technology, Boston Children's Hospital, Boston, Massachusetts, United States of America ; Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America ; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2013 Dec 23;8(12):e84951. doi: 10.1371/journal.pone.0084951. eCollection 2013.
Pediatric populations continue to be understudied in clinical drug trials despite the increasing use of pharmacotherapy in children, particularly with psychotropic drugs. Most pertinent to the clinical selection of drug interventions are trials directly comparing drugs against other drugs. The aim was to measure the prevalence of active drug comparators in neuropsychiatric drug trials in children and identify the effects of funding source on comparator selection. We analyzed the selection of drugs and drug comparisons in clinical trials registered between January 2006 and May 2012. Completed and ongoing interventional trials examining treatments for six neuropsychiatric conditions in children were included. Networks of drug comparisons for each condition were constructed using information about the trial study arms. Of 421 eligible trial registrations, 228 (63,699 participants) were drug trials addressing ADHD (106 trials), autism spectrum disorders (47), unipolar depression (16), seizure disorders (38), migraines and other headaches (15), or schizophrenia (11). Active drug comparators were used in only 11.0% of drug trials while 44.7% used a placebo control and 44.3% no drug or placebo comparator. Even among conditions with well-established pharmacotherapeutic options, almost all drug interventions were compared to a placebo. Active comparisons were more common among trials without industry funding (17% vs. 8%, p=0.04). Trials with industry funding differed from non-industry trials in terms of the drugs studied and the comparators selected. For 73% (61/84) of drugs and 90% (19/21) of unique comparisons, trials were funded exclusively by either industry or non-industry. We found that industry and non-industry differed when choosing comparators and active drug comparators were rare for both groups. This gap in pediatric research activity limits the evidence available to clinicians treating children and suggests a need to reassess the design and funding of pediatric trials in order to optimize the information derived from pediatric participation in clinical trials.
尽管儿童药物治疗的使用日益增加，尤其是精神药物，但儿科人群在临床药物试验中仍未得到充分研究。与药物干预的临床选择最相关的是直接将药物与其他药物进行比较的试验。目的是衡量儿童神经精神药物试验中活性药物对照的普遍性，并确定资金来源对对照选择的影响。我们分析了2006年1月至2012年5月期间注册的临床试验中的药物选择和药物比较。纳入了已完成和正在进行的针对儿童六种神经精神疾病治疗的干预试验。利用试验研究组的信息构建了每种疾病的药物比较网络。在421项符合条件的试验注册中，228项（63,699名参与者）是针对注意力缺陷多动障碍（106项试验）、自闭症谱系障碍（47项）、单相抑郁症（16项）、癫痫症（38项）、偏头痛和其他头痛（15项）或精神分裂症（11项）的药物试验。仅11.0%的药物试验使用了活性药物对照，而44.7%使用了安慰剂对照，44.3%未使用药物或安慰剂对照。即使在有成熟药物治疗选择的疾病中，几乎所有药物干预都与安慰剂进行了比较。在没有行业资金支持的试验中，活性对照更为常见（17%对8%；p=0.04）。有行业资金支持的试验在研究的药物和选择的对照方面与无行业资金支持的试验不同。对于73%（61/84）的药物和90%（19/21）的独特比较，试验完全由行业或非行业单独资助。我们发现，行业和非行业在选择对照时存在差异，且两组的活性药物对照都很少见。儿科研究活动中的这一差距限制了临床医生治疗儿童时可获得的证据，并表明需要重新评估儿科试验的设计和资金，以优化从儿科参与临床试验中获得的信息。
