NIRG: Patient and public INvolvement In target differeNces in Trials (The PINpoINT Study)

临床试验被认为是测试国民健康服务(NHS)提供哪些治疗方法的最佳方式。试验是为了让患者受益，因此他们的设计应该以患者为中心。尽管患者和公众参与(PPI)被认为是重要的，但患者和公众在关键试验数字方面很少有发言权(例如，我们在测试治疗时寻找多大的差异)。我们的目标是共同设计新的方法和工具，以提高患者和公众在试验设计和解释中的一个关键数字方面的参与度-目标差异。“正常”(优势)临床试验试图找出一种新的治疗方法是否比目前的治疗方法更好。一项非劣效性试验试图证明新的治疗方法并不比目前的治疗方法更差(但它可能还有其他优势，比如更低的成本或更好的安全性)。要提出治疗建议，新的治疗方法需要在一定程度上更好或足够好。这就是所谓的目标差异。大多数试验旨在发现对相关利益相关者重要的目标差异，但它们往往将患者排除在决策之外。例如，我们可能会进行一项试验，测试药物A和药物B治疗患者疼痛的效果。为了确定药物A是否比药物B更好，我们必须在患者报告的结果(疼痛)中定义目标差异。在这个例子中，疼痛是通过询问患者“你今天感觉有多痛？”来衡量的。在1(完全没有疼痛)到10(非常疼痛)的范围内。这项试验的目标可能是在试验10天后检测疼痛等级的差异2分。这意味着，如果药物A组的参与者在疼痛评分中的得分为3分，药物B组的参与者的得分为5.5分，我们将决定药物A是更好的治疗方法。但这对患者来说有价值吗？目前，目标差异决策通常基于(知情的)猜测，基于一个小团队的判断，这通常排除了公共合作伙伴(这里定义为患者或研究团队公共部分的成员)。包括患者和公共合作伙伴将确保试验在设计时考虑到患者的重要差异。这将与其他考虑因素一起告知目标差异，如试验成本和临床医生的观点。它还将支持对试验结果的解释，以帮助告知NHS提供哪些治疗方法。为了实现这一目标，我们建议：-与患者和公共合作伙伴合作开发包容性工具，以(A)支持研究团队对目标差异的共同理解；(B)在试验设计阶段有效地识别患者的重要差异；以及(C)在决定试验的最终目标差异之前，与公共合作伙伴就现有的目标差异进行有意义的讨论。我们将确定并使用当前的做法来支持这些工具的设计。-试点整个过程--从试验设计开始时确定可用的目标差异，到与试验团队中所有相关利益相关者(包括公共合作伙伴)举行最后会议，就目标差异达成共识-评估让患者和公共合作伙伴参与决定目标差异的可行性和影响，并为考虑到结果的试验者和公共合作伙伴起草指南。患者和公共合作伙伴不需要事先了解医疗统计数据就可以参与。这些工具的开发将使不同算力水平的人能够理解和使用。我们的项目已经制定，并将由一个咨询小组提供信息，其中包括三个有经验的公共合作伙伴。最终，该项目中开发的工具旨在通过将患者作为临床研究的基础来提高试验的相关性并减少研究浪费。

Clinical trials are considered the best way of testing which treatments are made available in the National Health Service (NHS). Trials are run to benefit patients and so patients should be central to their design. Even though patient and public involvement (PPI) is considered important, patients and the public rarely have a say in key trial numerical aspects (for example, how big of a difference we look for when testing treatments). We aim to co-design new methods and tools to improve the involvement of patients and the public in a key numerical aspect in trial design and interpretation - the target difference. A "normal" (superiority) clinical trial tries to find out whether a new treatment is better than the current treatment. A non-inferiority trial tries to show the new treatment is not worse than the current treatment (but it may have other advantages, like lower cost or better safety). To make a treatment recommendation, new treatments need to be better or good enough by a certain margin. This is called the target difference. Most trials aim to detect a target difference that is important to relevant stakeholders, but they often exclude patients from decision making. For example, we may have a trial testing drug A against drug B to treat pain in patients. To decide if drug A is better than drug B, we will have to define a target difference in the patient reported outcome (pain). In this example pain is measured by asking patients "How much pain do you feel today?" in a scale of 1 (no pain at all) to 10 (a lot of pain). The trial may aim to detect a difference of 2 points in the pain scale after 10 days of being in the trial. This means that if participants in the drug A group had a score of 3 points in the pain scale and participants in the drug B group had a 5.5 score, we would decide that drug A is a better treatment. But is that a worthwhile difference to patients?Currently, target difference decision making is usually based on (informed) guesswork based on a small team's judgement which often excludes public partners (defined here as patients or members of the public part of the research team). Including patients and public partners would ensure trials consider patient important differences when they are designed. This would inform the target difference along with other considerations, like the trial's costs and clinician's views. It would also support the interpretation of trial results that help inform which treatments are available in the NHS. To achieve this, we propose to:- Work with patients and public partners to develop inclusive tools to (a) support a common understanding of target differences in the research team; (b) enable an efficient identification of patient important differences at the trial design stage; and (c) enable a meaningful discussion of existing target differences with public partners ahead of deciding the final target difference for the trial. We will identify and use current practice to support the design of these tools.- Pilot the full process - from identification of available target differences at the start of trial design, to a final meeting with all relevant stakeholders in the trial team including public partners, where consensus about the target difference is reached - Assess the feasibility, and impact of involving patients and public partners in deciding the target difference and draft guidance for trialists and public partners considering the findingsPatients and public partners do not need to have a prior understanding of medical statistics to get involved. The tools will be developed to be understandable and accessible to people with different numeracy levels. Our project has been developed and will be informed by an advisory group including three experienced public partners. Ultimately, the tools developed in the project aim to improve the relevance of trials and reduce research waste by making patients the foundation of clinical research.