Comparison of Processed Nerve Allograft and Collagen Nerve Cuffs for Peripheral Nerve Repair

s2PD is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm (best case scenario value possible) and 15mm. The failure to respond to stimulus was pre-defined as the worst case scenario value possible (16mm). Missing or incomplete assessments were not imputed. This analysis was completed on the Per Protocol population, defined as subjects with at least 6 months follow-up and no major protocol violations. Data used for this analysis was from 6 months post-surgical follow-up to the date of each subject's latest completed s2PD assessment, whichever came last, assessed up to 12 months.

Time frame: Up to Month 12

Population: No interpolated data or modeling was used for this analysis. Results by length of nerve gap (gap 5-14mm vs. gap 15-25mm). As there is no pre-defined numerical value for absent response/failure in as-reported data, 'absent' results were not included in this analysis. This is the Per Protocol population which includes all patients in baseline population who have completed a minimum of 6 months follow-up and have no major protocol violations.

Static two-point discrimination (s2PD) is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm (best case scenario value possible) and 15mm. The failure to respond to stimulus was pre-defined as the worst case scenario value possible (16mm). Missing or incomplete assessments were imputed as the worst case scenario value possible (16mm). Missing or incomplete data was extrapolated using a pre-defined repeated measures mixed modeling approach for calculations in this analysis. This analysis was completed on the Per Protocol population, defined as subjects with at least 6 months follow-up and no major protocol violations.

Time frame: Month 12

Population: This is the Per Protocol population which includes all patients in baseline population who have completed a minimum of 6 months follow-up and have no major protocol violations. The analysis was performed using a pre-defined statistical analysis with a non-response/failure assigned a worst-case scenario value of 16mm.

The Visual Analog Scale (VAS) For Pain is a patient reported outcomes scale whereby the patient indicated their current pain level by making a mark on a continuous horizontal 10 centimeter (100 millimeter) line. The distance from the 0 millimeter to the patient's mark corresponds to the amount of pain the subject is currently experiencing. VAS for Pain data were recorded as the number of millimeters from the left of the line to the patients mark across the range of 0-100 millimeters, with 0 millimeter representing no pain and 100 millimeters representing the worst pain imaginable. This is the Intent To Treat population which includes all subjects that were randomized. The analysis was performed using a standard statistical analysis on Month 12 data. Missing or incomplete data was extrapolated using a pre-defined repeated measures modeling approach for calculations in this analysis.

Time frame: Month 12

Population: This is the Intent To Treat population which includes all subjects that were randomized. The analysis was performed using a standard statistical analysis on Month 12 data. The analysis compared Month 12 VAS to Baseline VAS within-group. No between-group analyses were conducted.

MRC classification score is a functional recovery classification. For nerves with sensory targets, outcomes resulting from static two-point discrimination and Semmes-Weinstein Monofilament pressure threshold testing are used to determine the classification score. Sensibility testing for the target repair was performed by a blinded assessor using a standardized discriminator tool and Semmes-Weinstein monofilaments. Upper bound response for static two-point discrimination was 15mm. This is the Intent To Treat population which includes all subjects that were randomized and have a reported value at Month 12. Scale range: Minimum S0 = 0 (no sensibility), S1=1, S2=2, S3=3, S3+=4, maximum S4 = 5 (normative levels of sensibility). Higher values represented better outcomes.

Time frame: Month 12

Population: This is the Intent To Treat population which includes all subjects that were randomized and have a reported value at Month 12. In this analysis of Month 12 data, MRCC scores are assigned numeric values: S0=0, S1=1, S2=2, S3=3, S3+=4, S4=5.

This is the ratio of sensibility at Month 12 relative to sensibility at baseline for which the contralateral control value at Month 12 was used, expressed as a percentage. Pre-injury baseline was defined as s2PD at Month 12 in the contralateral digit associated with the target digit. Percent recovery to Pre-Injury Baseline was defined as: change from Pre-Injury Baseline (Contralateral control value) divided by the Pre-Injury Baseline Value \*100. s2PD is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm and 15mm. The failure to respond to stimulus was pre-defined as the worst case scenario value possible (16mm). Missing or incomplete assessments were imputed as the worst case scenario value possible (16mm). This analysis was completed on the Intent-to-Treat population, defined as all subjects who were randomized.

Time frame: Month 12

Population: This is the Intent To Treat population which includes all subjects that were randomized and have a reported value at Month 12. The analysis was performed using a pre-defined statistical analysis with a non-response/failure assigned a worst-case scenario value of 16mm. Missing or incomplete data was extrapolated using a pre-defined repeated mixed measures modeling approach for calculations in this analysis.

This is the percentage of subjects who achieved sensibility as defined by s2PD 2mm-15mm at Month 12. s2PD is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm and 15mm. The failure to respond to stimulus was pre-defined as the worst case scenario value possible (16mm). Missing or incomplete assessments were imputed as the worst case scenario value possible (16mm). This analysis was completed on the Intent-to-Treat population, defined as all subjects who were randomized.

Time frame: Month 12

Population: This is the Intent To Treat population which includes all subjects that were randomized and have a reported value at Month 12. The analysis was performed using a pre-defined statistical analysis with a non-response/failure assigned a worst-case scenario value of 16mm. Missing or incomplete data was not included in this analysis of response rate.

Time to recovery of s2PD was defined as the number of months from Operative day to the return of sensory function (defined as Medical Research Council sensory function score of S3+ or greater) at Month 3, Month 6, Month 9, or Month 12. s2PD is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm and 15mm. S4 is s2PD of 2-6mm and S3+ is s2PD of 7-15mm. Those without S3+ and absent values were considered not recovered. This is the Intent To Treat population which includes all subjects that were randomized. Any subject with a value of s2PD of absent was considered not recovered and was therefore not included in this analysis.

Time frame: Assessed at Month 3, Month 6, Month 9, Month 12 (some patients were seen for their 12-month visit up to 15 calendar months post-op)

Population: This is the Intent To Treat population which includes all subjects that were randomized. Any subject with a value of s2PD of absent was considered not recovered and was therefore not included in this analysis.

A post-hoc analysis was performed to determine the gap length (in mm) at which a statistically significant difference in the recovery of sensibility between treatment groups could be detected. Data were grouped by gap length, starting with 15-25 and incrementally including additional gap lengths (i.e. 14, 13 and 12) when statistical significance was observed between groups. s2PD is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm and 15mm. Patients with a result of 'absent' were not included in this analysis. This analysis was completed on the Per Protocol population, defined as subjects with at least 6 months follow-up and no major protocol violations. Data used for this analysis was from 6 months post-surgical follow-up to the date of each subject's latest completed s2PD assessment, whichever came last, assessed up to 12 months.

Time frame: Up to Month 12

Population: No interpolated data or modeling was used for this analysis. As there is no pre-defined numerical value for absent response/failure in the data as-reported, patients with a result of 'absent' were not included in this analysis. This is the Per Protocol population which includes all subjects in baseline population who have completed a minimum of 6 months follow-up and have no major protocol violations.

A post-hoc analysis was performed to determine the difference between treatment groups in the time from index surgery to the recovery of sensibility in the target nerve repair by gap length interval. Data were grouped by gap length, starting with 15-25 and incrementally including additional gap lengths (i.e. 14, 13, 12, 11, and 10) when statistical significance was observed between groups. s2PD is measured by blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm and 15mm. Time to Recovery of sensibility is defined as the month of the subject's visit where they achieved subject's achievement of s2PD of 2-15 mm and maintained s2PD through their last visit. This analysis was completed on the Per Protocol population, defined as subjects with at least 6 months follow-up and no major protocol violations.

Time frame: Assessed at Month 3, Month 6, Month 9, and Month 12

Population: The failure to respond to stimulus was not recorded, thus only subjects with recovered sensibility are included in this data set. No interpolated data or modeling was used for this analysis. This is the Per Protocol population which includes all subjects in baseline population who have completed a minimum of 6 months follow-up and have no major protocol violations.

A post-hoc analysis was performed to determine the difference between treatment groups in the time from index surgery to the recovery of sensibility in the target nerve repair. s2PD is measured by a blinded assessor using a standardized discriminator tool that measures the innervation density and the subject's ability to discern between a single point and two distinct points between 2mm and 15mm. Time to Recovery of sensibility is defined as the month of the subject's visit where they achieved s2PD of 2-15 mm and maintained s2PD through their last visit. Missing or incomplete assessments were not imputed. This analysis was completed on the Per Protocol population, defined as subjects with at least 6 months follow-up and no major protocol violations.

Time frame: Assessed at Month 1, Month 3, Month 6, Month 9, Month 12

Population: No interpolated data or modeling was used for this analysis. This is the Per Protocol population which includes all subjects in baseline population who have completed a minimum of 6 months follow-up and have no major protocol violations. Results are a subset of the Per Protocol population by length of nerve gap for Month 1 to Month 12.

No interpolated data or modeling was used for this analysis. This analysis was completed for Adverse Event (AE) criteria related to pain and hypersensitivity (Pain, Pain in Extremity, Hypersensitivity, Hypersensitivity at implant site, Neuroma, and derivations of these descriptors) beginning after Operative Day (Operative Day+1). Revision surgeries for Pain-Related conditions documented as Ongoing were also included. Recovered/Resolved AEs were not included in the analysis unless the resolution was surgical revision. Unrelated AEs were also not included in this analysis. This is the Safety population which includes all subjects that received a nerve repair.

Time frame: Operative Day+1, Month 1, Month 3, Month 6, Month 9, Month 12

Population: No interpolated data or modeling was used for this analysis. This is the Safety population which includes all subjects that received a nerve repair.