ICRS 2019 - Conference Calendar

Displaying One Session

Plaza A Instructional Course
Session Type
Instructional Course
Date
07.10.2019
Time
07:30 - 08:30
Location
Plaza A
Extended Abstract (for invited Faculty only)

13.2.1 - What do Regulatory Bodies Want?

Presentation Number
13.2.1
Lecture Time
07:30 - 07:45
Session Type
Instructional Course
Corresponding Author
Extended Abstract (for invited Faculty only) Clinical Outcome

13.2.2 - The Challenges of Joint Preservation Trials

Presentation Number
13.2.2
Presentation Topic
Clinical Outcome
Lecture Time
07:45 - 08:00
Session Type
Instructional Course
Corresponding Author

Abstract

Introduction

Randomized Controlled Trials (RCTs) remain the gold standard for clinical research design. The advantages of randomization in eliminating or greatly reducing bias is largely considered to outweigh the loss of generalizability of a well-designed RCT. While this is undoubtedly true for pharmaceutical or biologic research, this is less clear for surgical studies. There are several unique challenges for surgical trials, both specific to cartilage repair and beyond. The primary challenges for surgical trials discussed in this talk will revolve around five primary areas: equipoise, recruitment, crossover, retention, and cost.

Content

Before a trial can even be successfully designed, equipoise must exist within trial investigators. That is, they must believe that they do not know which treatment alternative is superior and surgeon investigators must be willing to attempt to enroll every eligible patient into the trial. Otherwise, if individual surgeons have differing degrees of equipoise, the patients they enroll may be fundamentally different from what the trial’s equipoise expects.

Even the best designed and funded surgical RCTs have had tremendous difficulty with successful recruitment and randomization. For cartilage studies this is exacerbated by the very small number of eligible. Strict inclusion and exclusion criteria are necessary to ensure homogeneity and limit the effect of potential confounding factors, but they also result in very limited eligible patient cohorts. One recently completed cartilage trial successfully recruited and followed just 80 patients across 26 sites over 10 years. Beyond the limited number of patients available, it is often very difficult to convince eligible patients to allow the randomization of their surgery. With medications, the patient can always decide to stop taking the medication they are randomized to, but for surgery, there is no way to undo the decision and surgery once it’s been completed. For example, the METEOR trial on meniscal teat treatments successfully enrolled just 26.4% of eligible patients for what is essentially a standard treatment protocol.

Even once patients are successfully recruited, it can be a challenge to get them to comply with their randomization. For example, a higher proportion of patients in the SPORT trial for spine surgery that opted for an observational cohort rather than randomization ended up having surgery than in the group randomized to surgery. This has tremendous ramifications for interpretability if analyses are conducted as randomized rather than as treated. Crossover from nonsurgical to surgical intervention is also a concern. This crossover in both directions, again, makes for challenging interpretation.

Since surgical trials often require two to five years of follow-up to assure safety of implanted materials, retention of patients is also a challenge. Despite being engaged enough in their treatment to enroll in a randomized study, patients may migrate or lose contact with their surgeon over time. It will remain unknown if the patients were lost to follow-up due to feeling fine or due to dissatisfaction with their surgery unless it is possible to track them down. Again, this has serious effects on our ability to defend trial results if retention is low.

Finally, as a result of all of these above concerns and the very strict regulatory environment, RCTs are quite costly. In the case of cartilage repair, where eligible patients are very limited, multicenter trials may be the only feasible approach, which also adds costs due to logistical challenges of research across multiple sites. Many jurisdictions also require trials to pay for all treatments received by the patients so even the standard of care treatment group would have to have their treatment covered by the trial sponsor. This risk for device companies makes cartilage trials a challenging financial decision as a null trial could be very expensive and yield no return on the investment. This is compounded by the fact that the patient population eligible for the novel treatment may in itself be relatively small, limiting the potential for profits as a result of the research even if the trial is successful.

All in all, surgical trials for cartilage repair remain a very challenging area of research, but one for which we should continue to endeavor to succeed.

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Extended Abstract (for invited Faculty only) Others

13.2.3 - Industry Perspective

Presentation Number
13.2.3
Presentation Topic
Others
Lecture Time
08:00 - 08:15
Session Type
Instructional Course
Corresponding Author