Who has skin in the game? Expanding patient opportunities for research engagement is a win-win for dermatology.
Who has skin in the game? Expanding patient opportunities for research engagement is a win-win for dermatology.
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谁在游戏中拥有利益？
DOI：
10.1093/bjd/ljad394
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Petukhova,Lynn
中科院分区：
文献类型：
--
作者：
Colvin,Annelise;Petukhova,Lynn
牛皮癣是一种栖息在精准医学前沿的疾病实体。它有三个条件，为改善健康结果和医疗效率创造机会。它是一种流行疾病，拥有大量经批准的干预措施，并有证据表明生物病因和治疗反应存在异质性。仍然缺乏的是一种可靠的方法来预测哪些患者亚组对特定干预措施的反应最好--这些信息可以通过药物遗传学研究发现。虽然这一机会已经得到了几个组织的广泛认可和追求，但促进针对患者疾病制定治疗计划的遗传生物标记物出现得很慢。1获得药物反应结果既耗时又昂贵，这限制了队列规模和统计能力。在张等人的文章中。2在本期《英国医学杂志》上，由林C.蔡博士领导的团队描述了他们如何克服这一重大挑战，证明使用患者报告的结果(PRO)提供了一种在药物遗传学研究中增加样本量的有效方法。2之前关于银屑病的药物遗传学研究规模很小，研究参与者不到200人。相比之下，通过使用专业人士，张等人。能够聚集1942名银屑病基因分型研究参与者的队列。结果数据包括自我报告的疾病严重程度和对六种治疗的反应，包括口服系统疗法、肿瘤坏死因子(TNF)抑制剂、光疗和局部药物。他们的结果证明了统计能力的提高，包括40个P值和lt；5×10-6的基因座。虽然这些结果没有超过严格的统计阈值，说明了多种遗传变异和多种结果的测试，但他们进行了一系列生物信息学和实验验证研究，表明CD200与甲氨蝶呤的反应有关，并提供了KLK7调节角质形成细胞对肿瘤坏死因子的反应的证据。因此，他们的研究确定了新的遗传生物标记物，并提出了一种改善患者对肿瘤坏死因子抑制反应的分子方法。2需要进行重复研究。精准医学倡议的揭幕伴随着一种新的研究范式的展示，一种由患者参与推动的研究范式。3研究参与者被视为生物医学和临床研究的积极合作伙伴，提供丰富的结果描述，并在很长一段时间内访问他们的保健数据和捐赠的生物标本。这种重组不仅改善了研究的设计和权力，而且在发展和维护公众信任方面也发挥了关键作用。此外，它还有助于为新的医疗保健模式奠定基础，在这种模式下，患者积极帮助管理自己的健康，并帮助提出和回答新的研究问题，促进共享决策。4张氏等人。这项研究提供了经验证据，表明为研究参与者提供报告他们的经验和参与研究过程的机会可以导致发现，这些发现可能会改善他们的疾病的临床管理。2而张氏等人所使用的数据。在回顾收集这项研究之后，社会和行为科学正在积极推进从研究参与者那里实时和在其自然环境中收集数据的前瞻性方法。5如此一来，张等人提出了自己的观点。这项研究还鼓励将这些方法更好地整合到皮肤病研究中，进一步增强患者作为合作伙伴的能力。
Psoriasis is a disease entity perched at the forefront of precision medicine. It has a trifecta of conditions that creates opportunities for improving health outcomes and healthcare efficiency. It is a prevalent disease with an arsenal of approved interventions and evidence for heterogeneity in biologic causes and treatment responses. What remains missing is a reliable way to predict which patient subsets will have the best responses to particular interventions–information that can be discovered with pharmacogenetic studies. While this opportunity has been widely recognized and pursued by several groups, genetic biomarkers that facilitate the development of treatment plans tailored to a patient’s disease have been slow to emerge for psoriasis. 1 Obtaining drug response outcomes is time consuming and expensive, which limits cohort sizes and statistical power. In the article by Zhang et al. 2 in this issue of the BJD, the team led by Dr Lam C. Tsoi describes how they have overcome this major challenge, demonstrating that the use of patient-reported outcomes (PROs) provides an efficient way to increase sample sizes in pharmacogenetic studies. 2 Prior pharmacogenetic studies in psoriasis were small, containing fewer than 200 research participants. In contrast, by using PROs, Zhang et al. were able to assemble a cohort of 1942 genotyped psoriatic research participants. Outcome data included self-reported disease severity and responses for six treatments including oral systemic therapies, tumour necrosis factor (TNF) inhibitors, phototherapy and topical medications. The improved statistical power is evidenced by their results, which include 40 loci with P-values< 5× 10–6. While these results do not exceed stringent statistical thresholds that account for testing of multiple genetic variants and multiple outcomes, they performed a series of bioinformatic and experimental validation studies that implicate CD200 in methotrexate response and provide evidence that KLK7 regulates keratinocyte responses to TNF. Thus, their study identifies new genetic biomarkers and suggests a molecular approach to improving patient responses to TNF inhibition. 2 Replication studies are needed. The unveiling of precision medicine initiatives was accompanied by the presentation of a new research paradigm, one powered by patient engagement. 3 Research participants are reconceived as active partners in biomedical and clinical research, providing rich descriptions of outcomes and access to their healthcare data and donated biospecimens over long time periods. This reframing not only improves study designs and power, but also plays a critical role in developing and maintaining public trust. Furthermore, it helps lay a foundation for a new model of healthcare in which patients actively help to manage their own health and help to raise and answer new research questions, facilitating shared decision-making. 4 The Zhang et al. study provides empirical evidence that providing research participants an opportunity to report their experiences and engage in the research process can lead to discoveries that may improve the clinical management of their disease. 2 While the data used in the Zhang et al. study was retrospectively collected, social and behavioural sciences are actively advancing methods for the prospective collection of data from research participants in real time and in their natural environments. 5 Thus, the Zhang et al. study also incentivizes a better integration of these methods into dermatological research, further empowering patients as partners.