Pictured: Four people with their thumbs up in approval/iStock, PeopleImages

图：四个人大拇指认可/反对，PeopleImages

The FDA’s Oncologic Drugs Advisory Committee on Wednesday voted in favor of US WorldMeds’ investigational drug eflornithine hydrochloride (DFMO) for the reduction of relapse risk in pediatric patients with high-risk neuroblastoma.

美国食品及药物管理局肿瘤药物咨询委员会周三投票赞成美国WorldMeds的研究药物盐酸依氟鸟氨酸（DFMO）降低高危神经母细胞瘤儿科患者的复发风险。

In a 14-6 vote, the panel of external experts found that even without a randomized controlled trial (RCT), US WorldMeds had provided enough evidence to conclude that DFMO boosts event-free survival in its target patient population.

在14-6票中，外部专家小组发现，即使没有随机对照试验（RCT），美国WorldMeds也提供了足够的证据来推断DFMO可提高其目标患者群体的无事件生存率。

“I believe that the data for event-free survival is compelling,” Christopher Lieu, committee chairperson and director of the Gastrointestinal Medical Oncology Program at the University of Colorado, said during the meeting. Lieu voted yes, but also noted that the lack of randomization likely could have overestimated the benefit of DFMO in the data presented during the session..

科罗拉多大学胃肠内科肿瘤学项目委员会主席兼主任克里斯托弗·刘（Christopher Lieu）在会议期间说：“我相信无事件生存的数据是令人信服的。Lieu投票赞成，但也指出缺乏随机化可能会高估DFMO在会议期间提供的数据中的益处。。

“Having said that, this is a therapeutic that has relatively lower toxicity compared to what we typically discuss,” Lieu said in explaining his vote. “I believe that the expected benefits outweigh the risks of treatment.”

Lieu在解释他的投票时说：“尽管如此，与我们通常讨论的相比，这是一种毒性相对较低的治疗方法。“我相信预期的好处大于治疗的风险。”

Still, in his summary of the panel’s votes and rationales, Lieu pointed to worries that this might lead to a “slippery slope” in terms of the degree of clinical evidence that will be required of future drug applications in similar rare and difficult-to-study indications. The panelists who voted against DFMO raised similar concerns..

尽管如此，Liu在对专家组投票和理由的总结中指出，担心这可能导致临床证据的程度“滑坡”，这将是未来药物应用在类似的罕见和难以研究的适应症。投票反对DFMO的小组成员也提出了类似的担忧。。

“There is a lot of concern from the group about what the future holds for drug development and what level of evidence the FDA will require in similar situations in the future,” Lieu said.

Lieu说：“该组织非常关注未来药物开发的前景以及FDA将来在类似情况下需要什么样的证据水平。”。

In its application for DFMO, US WorldMeds provided data from a prospective Phase II, multicenter, open-label, single-arm study of DFMO maintenance treatment in patients who had completed multiagent and multimodality therapy.

在DFMO的应用中，美国WorldMeds提供了来自完成多药物和多模式治疗的患者的DFMO维持治疗的前瞻性II期，多中心，开放标签，单臂研究的数据。

In a briefing document posted ahead of the adcomm meeting, US WorldMeds said that they had been told by the FDA that an RCT is the “preferred path to registration” for these types of drugs. However, given the challenges of conducting a randomized study in rare diseases, the company instead proposed an external control approach..

在adcomm会议之前发布的简报文件中，美国WorldMeds表示，FDA已告知他们RCT是这些类型药物的“首选注册途径”。然而，鉴于在罕见疾病中进行随机研究的挑战，该公司反而提出了一种外部控制方法。。

The company then drew from a retrospective chart review of patients with high-risk neuroblastoma and also worked collaboratively with the FDA to design a “rigorous propensity score matched analysis” using a landmark study as its external control.

然后，该公司对高危神经母细胞瘤患者进行了回顾性图表审查，并与FDA合作设计了一项“严格的倾向评分匹配分析”，并使用一项具有里程碑意义的研究作为外部控制。

In its own briefing document, the FDA noted that US WorldMed’s use of an external control in this situation is “reasonable” but also conceded that there are “inherent limitations” associated with externally controlled data, such as interpreting the estimated treatment effect of an investigational intervention..

FDA在其自己的简报文件中指出，美国WorldMed在这种情况下使用外部控制是“合理的”，但也承认外部控制数据存在“固有限制”，例如解释研究干预的估计治疗效果。。

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Tristan Manalac是位于菲律宾大马尼拉的独立科学作家。他可以联系到tristan@tristanmanalac.com或者tristan.manalac@biospace.com.