Background:

Commercially available products used in knee cartilage reconstructive and restorative surgical practices fall under unique US Food and Drug Administration (FDA) regulatory pathways that determine the level of evidence required to market each product.

Purpose:

To evaluate the levels of evidence in the literature supporting commercially available cartilage repair procedures stratified by FDA regulatory pathway (section 351 vs section 361 of “Human Cells, Tissues, and Cellular and Tissue-Based Products” [HCT/P] in the Code of Federal Regulation) with the hypothesis that products requiring approval under a stringent regulatory pathway (351 HCT/P) have higher levels of evidence in the literature supporting use and that products with a less stringent regulatory pathway (361 HCT/P) have a higher number of products available for use in the United States.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

A search of the PubMed database was performed to identify all peer-reviewed articles pertaining to either allograft or autologous cartilage repair technologies. Predefined inclusion and exclusion criteria were used to find clinical, preclinical, and laboratory studies while excluding duplicates, systematic reviews, and products not available in the United States. Articles were categorized by regulatory pathway (351 and 361 HCT/P), and variables including publication year, type of publication, level of evidence, and number of publications were analyzed.

Results:

After application of predefined criteria, 470 of 1924 articles were included in this study. The 351 HCT/P group was composed entirely of autologous chondrocyte implantation (ACI) technology; 94% of the 361 HCT/P group was composed of osteochondral allografts (OCA). The articles regarding 351 HCT/P were more likely to be clinical in nature than the articles on 361 HCT/P (80% vs 48%, respectively; P = .0001) and entailed significantly more level 1 studies (25 vs 0, respectively; P < .0001). Twice as many articles in the 351 HCT/P group were published in the American Journal of Sports Medicine compared with the 361 HCT/P group (71 vs 38, respectively; P = .18).

Conclusion:

Both ACI and OCA have robust evidence supporting their use, whereas the remaining regulated products have little or no supporting evidence. Technologies regulated by 351 HCT/P were more likely to be level 1 clinical studies and published in the highest impact journal. The 361 HCT/P pathway regulated many more products, with fewer articles supporting their use.

中文翻译：

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按 FDA 批准途径分层的市售膝关节软骨修复技术评估

背景：

用于膝关节软骨重建和修复手术的市售产品属于美国食品和药物管理局 (FDA) 独特的监管途径，该途径决定了每种产品上市所需的证据水平。

目的：

评估文献中支持按 FDA 监管途径分层的市售软骨修复程序的证据水平（《美国食品和药物管理局法典》第 351 节与“人体细胞、组织以及细胞和组织产品”[HCT/P] 的第 361 节） Federal Regulation），假设需要根据严格的监管途径获得批准的产品（351 HCT/P）在支持使用的文献中有更高水平的证据，而监管途径不太严格的产品（361 HCT/P）有更高的数量可在美国使用的产品。

学习规划：

系统审查；证据等级，4。

方法：

对 PubMed 数据库进行了搜索，以确定所有与同种异体移植或自体软骨修复技术相关的同行评审文章。使用预定义的纳入和排除标准来查找临床、临床前和实验室研究，同时排除重复、系统评价和在美国不可用的产品。文章按监管途径（351 和 361 HCT/P）分类，并分析了包括出版年份、出版类型、证据水平和出版物数量在内的变量。

结果：

应用预定义标准后，1924 篇文章中的 470 篇被纳入本研究。351 HCT/P组完全采用自体软骨细胞移植（ACI）技术；94% 的 361 HCT/P 组由骨软骨同种异体移植物 (OCA) 组成。关于 351 HCT/P 的文章比关于 361 HCT/P 的文章更可能是临床性质的（分别为 80% 和 48%；P = .0001），并且需要更多的 1 级研究（分别为 25 和 0 ; P < .0001)。与 361 HCT/P 组相比，351 HCT/P 组在美国运动医学杂志上发表的文章数量是 361 HCT/P 组的两倍（分别为 71 篇和 38 篇；P = .18）。

结论：

ACI 和 OCA 都有强有力的证据支持它们的使用，而其余的受监管产品几乎没有或没有支持证据。受 351 HCT/P 监管的技术更有可能成为 1 级临床研究并发表在影响力最高的期刊上。361 HCT/P 途径监管更多的产品，支持其使用的文章更少。