September 3, 2024
By Dwight Akerman, OD, MBA, FAAO, FBCLA, FIACLE
Evidence-based eye care is a crucial approach in providing the best possible treatment for juvenile-onset myopia. By relying on evidence-based practices, eye care practitioners can ensure that their interventions are rooted in sound scientific research and proven efficacy. This approach involves thoroughly analyzing peer-reviewed papers, clinical studies, and statistical data to understand the safety and effectiveness of different interventions.
By adopting evidence-based practices, eye care professionals can make informed decisions about incorporating new interventions into their clinical myopia management armamentarium. This ensures that children, adolescents, and young adults receive the highest quality and most effective care for slowing the progression of myopia, ultimately contributing to better long-term eye health.
Practitioners must be familiar with statistical terms such as intention-to-treat (ITT) analysis, protocol deviations, adjusted treatment effects, and per-protocol analysis when evaluating myopia management strategies. Understanding these terms is essential for accurately assessing the validity and significance of research findings.
When eye care professionals assess peer-reviewed clinical papers involving myopia management interventions, it is critical to understand the data and statistics being presented. Similarly, it is essential to understand the data and statistics supporting product marketing claims. Here are several statistical terms that you need to be familiar with in order to understand myopia management research fully.
- An intention-to-treat (ITT) analysis is a method for analyzing results in a prospective randomized controlled trial (RCT.) All randomized participants are included in the statistical analysis and analyzed according to the group they were initially assigned, regardless of what treatment (if any) they received. Applying the intention-to-treat principles yields an unbiased estimate of the safety outcomes at the level of adherence observed in the trial. Thus, it is required for safety evaluations. Protocol deviations happen during clinical trials. Subjects who did not meet enrollment criteria may have been mistakenly enrolled. A piece of equipment may be calibrated at the wrong setting during certain visits, or the study procedure may have been miscommunicated to the subjects. Also, subjects in clinical trials do not always adhere to the protocol. For example, subjects may have stopped treatment for a period of time or did not comply with the study procedure, e.g., contact lens wearing time during weekends. Protocol deviations can have significant implications that impact the results and analysis of a study. So, when the treatment under study is effective, but there is substantial nonadherence, the intention-to-treat efficacy analysis may underestimate the significance of the treatment effect that will occur in adherent patients.
Modified ITT, a subgroup analysis, may apply when there is a reason to examine a particular segment of the population (e.g., a narrower age range). For example, during a meta-analysis, it may be necessary to match the population characteristics of other RCT studies and enable a more accurate comparison among RCT results. - Both Unadjusted and Adjusted treatment effects have been reported in many studies on myopia control. The Unadjusted treatment effects are calculated by simply averaging (simple mean) the outcome measures from the study population. However, there are other factors, such as age, gender, parental myopia, baseline refractive error, and ethnicity, which may also influence the progression of myopia (covariates). The Adjusted treatment effect is obtained by using a statistical method, a type of regression analysis called Linear Mixed Model, which considers the covariate values associated with each study subject. This method helps to remove the potential impacts from the covariates, making the Adjusted results a better representation of the actual effect of the intervention being studied. Therefore, the application of Adjusted data in peer-reviewed journals and its requirement by regulatory agencies, such as the FDA, underscores its importance and validity.
- Per protocol analysis ignores data with protocol deviations. This is typically reported as the product efficacy in marketing claims because only adherent children are included in the reported results, often resulting in far more robust efficacy claims. For example, in virtually all clinical trials for myopia control optical devices (contact lenses and spectacles), the protocol requires that subjects wear the device a minimum of 12 hours per day and six days per week. If the subjects consistently violate the required wearing time, they are excluded from a per-protocol analysis, resulting in far more robust efficacy claims.
- Data from myopia control clinical trials are occasionally presented as Statistically Significant, but they are not Clinically Significant. For example, in the NEI-funded COMET Trial (Gwiazda 2003), a statistically but not clinically significant effect was found. Myopic children wearing +2.00D PALs over three years resulted in a 0.20D reduction in the spherical equivalent progression compared to single-vision spectacles (control.) The three-year difference in progression of 0.20D between the two groups was statistically significant but hardly clinically significant.
I encourage all eye care practitioners to consider these points when reading the literature and assessing a new intervention for myopia management. If they do, they can weigh whether the intervention is worth adding to their clinical myopia management armamentarium. As eye care professionals, we must do everything possible to give children, adolescents, and young adults the highest quality care.
Best professional regards,
Dwight H. Akerman, OD, MBA, FAAO, FBCLA, FIACLE
Chief Medical Editor
dwight.akerman@gmail.com
