Bullimore Mark A, Brennan Noel A, Flitcroft Daniel Ian
College of Optometry, University of Houston, Houston, Texas, USA.
Johnson & Johnson Vision, Jacksonville, Florida, USA.
Ophthalmic Physiol Opt. 2023 May;43(3):525-533. doi: 10.1111/opo.13120. Epub 2023 Mar 10.
In the field of myopia control, effective optical or pharmaceutical therapies are now available to patients in many markets. This creates challenges for the conduct of placebo-controlled, randomised clinical trials, including ethics, recruitment, retention, selective loss of faster progressors and non-protocol treatments: Ethics: It is valid to question whether withholding treatment in control subjects is ethical. Recruitment: Availability of treatments is making recruitment into clinical trials more difficult. Retention: If masking is not possible, parents may immediately withdraw their child if randomised to no treatment. Selective loss: Withdrawal of fast progressors in the control group leading to a control group biased towards low progression. Non-protocol treatment: Parents may access other myopia treatments in addition to those within the trial. We propose that future trials may adopt one of the following designs: Non-inferiority trials using an approved drug or device as the control. The choice will depend on whether a regulatory agency has approved the drug or device. Short conventional efficacy trials where data are subsequently entered into a model created from previous clinical trials, which allows robust prediction of long-term treatment efficacy from the initial efficacy. Virtual control group trials based on data relating to axial elongation, myopia progression or both, accounting for subject's age and race. Short-term control data from a cohort, for example, 1 year or less, and applying an appropriate, proportional annual reduction in axial elongation to that population and extrapolating to subsequent years. Time-to-treatment-failure trials using survival analysis; once a treated or control subject progresses or elongates by a given amount, they exit the study and can be offered treatment. In summary, the future development of new treatments in myopia control will be hampered if significant changes are not made to the design of clinical trials in this area.
在近视控制领域，目前许多市场的患者都可获得有效的光学或药物治疗方法。这给开展安慰剂对照的随机临床试验带来了挑战，包括伦理、招募、留存、进展较快者的选择性失访以及非方案治疗等方面：伦理：质疑对对照组受试者不给予治疗是否符合伦理是合理的。招募：治疗方法的可获得性使得招募受试者参与临床试验变得更加困难。留存：如果无法进行盲法，若孩子被随机分配到无治疗组，家长可能会立即让其退出。选择性失访：对照组中进展较快者退出，导致对照组偏向低进展情况。非方案治疗：家长可能会在试验之外让孩子接受其他近视治疗。我们建议未来的试验可采用以下设计之一：使用已获批的药物或器械作为对照的非劣效性试验。具体选择将取决于监管机构是否已批准该药物或器械。短期传统疗效试验，随后将数据输入根据先前临床试验创建的模型，该模型能够根据初始疗效可靠地预测长期治疗效果。基于与眼轴伸长、近视进展或两者相关的数据进行虚拟对照组试验，同时考虑受试者的年龄和种族。来自队列的短期对照数据，例如1年或更短时间，并对该人群应用适当的、成比例的年度眼轴伸长减少量，然后外推至后续年份。使用生存分析的治疗失败时间试验；一旦治疗组或对照组受试者进展或伸长达到给定程度，他们就退出研究并可接受治疗。总之，如果该领域临床试验设计不做出重大改变，近视控制新疗法的未来发展将受到阻碍。
