Date Published: March 5, 2019
Publisher: Public Library of Science
Author(s): Charles J. Gerardo, Joao R. N. Vissoci, Leonardo P. de Oliveira, Victoria E. Anderson, Eugenia Quackenbush, Brandon Lewis, S. Rutherfoord Rose, Spencer Greene, Eric A. Toschlog, Nathan P. Charlton, Michael E. Mullins, Richard Schwartz, David Denning, Kapil Sharma, Kurt Kleinschmidt, Sean P. Bush, Nicklaus P. Brandehoff, Eric J. Lavonas, Chung-Ying Lin.
Valid, reliable, and clinically relevant outcome measures are necessary in clinical studies of snake envenomation. The aim of this study was to evaluate the psychometric (validity and reliability) and clinimetric (minimal clinically important difference [MCID]) properties of the Patient-Specific Functional Scale (PSFS) in snakebite envenomation.
We performed a secondary analysis of two existing snakebite trials that measured clinical outcomes using the PSFS as well as other quality of life and functional assessments. Data were collected at 3, 7, 10, and 17 days. Reliability was determined using Cronbach’s alpha for internal consistency and the intraclass correlation coefficient (ICC) for temporal stability at 10 and 17 days. Validity was assessed using concurrent validity correlating with the other assessments. The MCID was evaluated using the following criteria: (1) the distribution of stable patients according to both standard error of measurement (SEM) and responsiveness techniques, and (2) anchor-based methods to compare between individuals and to detect discriminant ability of a positive change with a receiver operator characteristic (ROC) curve and optimal cutoff point.
A total of 86 patients were evaluated in this study. The average PSFS scores were 5.37 (SD 3.23), 7.95 (SD 2.22), and 9.12 (SD 1.37) at 3, 7, and 10 days, respectively. Negligible floor effect was observed (maximum of 8% at 3 days); however, a ceiling effect was observed at 17 days (25%). The PSFS showed good reliability with an internal consistency of 0.91 (Cronbach’s alpha) (95% CI 0.88, 0.95) and a temporal stability of 0.83 (ICC) (95% CI 0.72, 0.89). The PSFS showed a strong positive correlation with quality of life and functional assessments. The MCID was approximately 1.0 for all methods.
With an MCID of approximately 1 point, the PSFS is a valid and reliable tool to assess quality of life and functionality in patients with snake envenomation.
Snake envenomation is a common public health problem worldwide with annual estimates ranging from 421,000 to 1,842,000 cases per year, with 20,000 to 94,000 deaths per year.[1–3] The burden of disease is particularly pronounced in low- and middle-income countries, and has been reclassified as a neglected tropical disease by the World Health Organization, leading to further interest in the field.[2, 4, 5] Potential new therapies are being developed that will require clinical trials.[6–9] However, the existing literature lacks data regarding patient-centered outcome measures for use in snake envenomation clinical trials. Consequently, prior trials have primarily used diagnosis-oriented endpoints, such as surrogate markers of coagulopathy, as primary outcomes.[11–15] Outcome measures that are patient centered and ideally patient reported will yield the most informative and clinically relevant information from the clinical trials evaluating potential snake envenomation therapies.
Our sample was composed of 86 patients. The average age was 43.0 (SD 17.6) years, and the participants were mostly white (87%). Slightly more male patients (52%) participated in the study. Eight patients (9%) were adolescents. Most patients had lower extremity injuries (62%). When completing the PSFS, the main activities chosen by the participants were activities of daily living (e.g., carrying items, climbing stairs, providing self-care), sports and exercise (e.g., running, swimming, collective sports), and specific body movements (e.g., flexing the affected hand, moving a finger). Work-related activities represented only 11% of all activities chosen. (Table 1)
The PSFS has been widely used with other clinical populations; however, to date, no previous study has evaluated the reliability, temporal stability, and MCID of the PSFS in patients with snake envenomation. Our results demonstrate that the PSFS is reliable, stable over time, externally valid, and strongly correlated with extremity functional assessment and other indicators of quality of life. The MCID was approximately 1.0 using multiple methodologies. This finding is important because the PSFS has been increasingly used as a patient-reported outcome measure due to its internal flexibility of content and ease of use. These results inform the clinical significance of prior clinical trials and further refine a potential outcome measure for future snake envenomation studies.
The PSFS is a valid, reliable tool in snake envenomation with good internal consistency, temporal stability, external validity, and correlation with other assessment tools, and this instrument is responsive to change. The PSFS should be considered an outcome measure of recovery of limb function due to tissue injury in future snake envenomation trials with an MCID of approximately 1 point.