医学伦理指南要求临床试验研究者和申办者告知前瞻性试验参与者与研究医疗产品相关的所有已知和潜在风险。并获得他们的自由知情同意。这些指南还要求临床研究的设计应尽量减少危害并最大化收益。
■研究默克公司在GardasilHPV疫苗许可前临床试验中使用含反应性铝的“安慰剂”的科学原理。
我们检查了在丹麦进行的FUTUREIIGardasil疫苗试验的知情同意书和招募手册;我们采访了几位FUTUREII试验参与者及其治疗医生。我们还审查了与Gardasil疫苗批准过程相关的监管文件以及关于评估人类疫苗中使用的佐剂的指南。
发现疫苗制造商默克公司向试验参与者做出了一些不准确的陈述,损害了他们的知情同意权。首先,尽管研究方案将安全性测试列为研究的主要目标之一,招聘手册强调FUTUREII不是一项安全研究,疫苗已经被证明是安全的。第二,试验的广告材料和知情同意书指出安慰剂是盐水或非活性物质,when,事实上,它含有默克公司专有的高反应性铝佐剂,该佐剂似乎没有经过适当的安全性评估。几个试验参与者经历了慢性致残症状,包括一些随机分配到佐剂“安慰剂”组。
■在我们看来,在Gardasil临床试验中使用反应性安慰剂没有任何可能的益处,不必要地将研究对象暴露在风险中,因此违反了医学伦理。在疫苗临床试验中常规使用铝佐剂作为“安慰剂”是不合适的,因为它阻碍了疫苗相关安全信号的发现。
UNASSIGNED: Medical ethics guidelines require of clinical trial investigators and sponsors to inform prospective trial participants of all known and potential risks associated with investigational medical products, and to obtain their free informed consent. These guidelines also require that clinical research be so designed as to minimize harms and maximize benefits.
UNASSIGNED: To examine Merck\'s scientific rationale for using a reactogenic aluminum-containing \"placebo\" in
Gardasil HPV vaccine pre-licensure clinical trials.
UNASSIGNED: We examined the informed consent form and the recruitment brochure for the FUTURE II
Gardasil vaccine trial conducted in Denmark; and we interviewed several FUTURE II trial participants and their treating physicians. We also reviewed regulatory documentation related to
Gardasil vaccine approval process and the guidelines on evaluation of adjuvants used in human vaccines.
UNASSIGNED: It was found that the vaccine manufacturer Merck made several inaccurate statements to trial participants that compromised their right to informed consent. First, even though the study protocol listed safety testing as one of the study\'s primary objectives, the recruitment brochure emphasized that FUTURE II was not a safety study, and that the vaccine had already been proven safe. Second, the advertising material for the trial and the informed consent forms stated that the placebo was saline or an inactive substance, when, in fact, it contained Merck\'s proprietary highly reactogenic aluminum adjuvant which does not appear to have been properly evaluated for safety. Several trial participants experienced chronic disabling symptoms, including some randomized to the adjuvant \"placebo\" group.
UNASSIGNED: In our view, the administration of a reactive placebo in
Gardasil clinical trials was without any possible benefit, needlessly exposed study subjects to risks, and was therefore a violation of medical ethics. The routine use of aluminum adjuvants as \"placebos\" in vaccine clinical trials is inappropriate as it hinders the discovery of vaccine-related safety signals.