Roche Pharma AG.
Medical School of Hanover, Hanover, Germany; r-connect ltd.
Value Health. 2021 May;24(5):744-752. doi: 10.1016/j.jval.2020.11.016. Epub 2021 Feb 18.
Health technology assessments (HTA) rely on head-to-head comparisons. We searched for intraindividual comparisons (IIC) qualifying as head-to-head design to develop comparative evidence.
Gemeinsamer Bundesausschuss (G-BA) appraisals between January 2011 and April 2020 were reviewed for inclusion of IIC. Identified IIC were grouped according to disease characteristics into nonprogressive, progressive, irregular, or symmetrical conditions. Evaluation of IIC by Institut für Qualität und Wirschaftlichkeit im Gesundheitswesen (IQWIG) and acceptance of IIC by G-BA were determined, and criteria for the usage and quality of IIC were developed.
A total of 483 appraisals finalized between January 2011 and April 2020 were reviewed. Eleven appraisals included IIC: nonacog beta (hemophilia B), turoctocog alpha (hemophilia A), emicizumab (2 appraisals: hemophilia A), pasireotide (unresectable pituitary tumor), lomitapid (homozygous familial hypercholesterolemia), glycerol phenylbutyrate (2 appraisals: urea cycle disorders), asfotase alfa (hypophosphatasia), lumacaftor (cystic fibrosis), and larotrectinib (NTRK solid tumors). All those appraisals related to rare genetic conditions with hemophilia and its bleeding rate are considered mainly a nonprogressive condition. All the other diseases show progressive disease characteristics. None of the identified IIC has been accepted by G-BA. Inconsistencies of before/after study design, lack of clarity on treatments prior to the switch, and different time intervals were among the most commonly cited methodological concerns.
IICs provide a rare opportunity to determine comparative effectiveness in distinct clinical settings that are not suitable or difficult to randomize into parallel groups. While manufacturers and researchers should aim for highest methodological standards when running an IIC, HTA bodies should accept IIC in distinct settings when determining relative effectiveness.
卫生技术评估（HTA）依赖于头对头比较。我们寻找符合头对头设计的个体内比较（IIC），以开发比较证据。
对 Gemeinsamer Bundesausschuss（G-BA）2011 年 1 月至 2020 年 4 月的评估进行了审查，以确定是否包含 IIC。根据疾病特征，将确定的 IIC 分为非进行性、进行性、不规则或对称条件。评估了 Institut für Qualität und Wirschaftlichkeit im Gesundheitswesen（IQWIG）对 IIC 的评估和 G-BA 对 IIC 的接受情况，并制定了 IIC 的使用和质量标准。
共审查了 2011 年 1 月至 2020 年 4 月期间完成的 483 项评估。有 11 项评估包括 IIC：非乙酰化β（血友病 B）、turoctocog alpha（血友病 A）、emicizumab（2 项评估：血友病 A）、pasireotide（不可切除的垂体肿瘤）、lomitapid（家族性高胆固醇血症）、甘油苯丁酸（2 项评估：尿素循环障碍）、asfotase alfa（低磷酸酶症）、lumacaftor（囊性纤维化）和 larotrectinib（NTRK 实体瘤）。所有这些评估都与血友病及其出血率等主要为非进行性疾病的罕见遗传疾病有关。其他所有疾病均表现出进行性疾病特征。未被 G-BA 接受的 IIC。在研究设计前后不一致、在转换前治疗方案不明确以及时间间隔不同等方面存在争议。
IIC 为在不适合或难以随机分组为平行组的特定临床环境中确定比较疗效提供了难得的机会。虽然制造商和研究人员在进行 IIC 时应努力达到最高的方法标准，但 HTA 机构在确定相对疗效时应接受特定环境中的 IIC。
