Immediate Accelerated Shoulder Rehabilitation (IASR) vs. Standard Protocol following Reverse Total Shoulder Arthroplasty: A Randomized Controlled Trial.

Background : Recently, the reverse total shoulder arthroplasty (rTSA) became the most frequently performed form of shoulder replacement in the United States and abroad. While physical therapy is universally accepted and routinely practiced, published postoperative rehabilitation guidelines and modifications are based on protocols developed in 1975. Since then, the principle components and temporal concepts of timing and intensity of postoperative rehabilitation and protected immobilization have been controversially applied and expertly discussed without a prevailing consensus. Comparative literature that prospectively addresses treatment differences, influences on outcomes, and superiority or inferiority versus control does not exist. Thus, the objective of this pilot study is to compare an accelerated and immediate active shoulder rehabilitation (IASR) rehabilitation program with standard care in patients following rTSA. Methods : A prospective, randomized, controlled, parallel-designed, two-armed, non-blinded, superiority pilot trial. The comparator arms are an accelerated rehabilitation (IASR) strategy versus standardized care following rTSA (CPT: 23472). The primary outcome measures will be the change from pre-surgical baseline to 52 weeks post-surgery in the American Shoulder and Elbow (ASES) score, Simple Shoulder Test (SST), and global health assessment (PROMIS-10. Secondary and tertiary outcomes will assess subscapularis integrity, implant status, and overall rehabilitation costs compared to formal control. Patients will be recruited from a single site (TRIA Orthopaedic Center, Bloomington, MN) neighboring the fourteenth largest US metropolitan area. Discussion : This trial will be the first study to compare the efficacy and safety of two different postoperative rehabilitation strategies for patients following rTSA. Further, this will be the first study to investigate an accelerated rehabilitation program without a period of protected immobilization following rTSA. Finally, the results will assist in the “general,” 3 problems, fatigue and in the last 7 Raw subscale scores for physical and mental health each are calculated out of 20. The raw score are converted to T scores for physical and mental health using the following formulas: the Global Physical Health score is generated by summing responses to Global03, Global06, Global07rescored, and Global08rescored. The Global Mental Health score is generated by summing responses to Global02, Global04, Global05, and Global10rescored. T scores range from 0–100. A high score represents a better outcome. There is not a total score for this tool. The 10 questions of the Global–10 have primarily been adapted from other frequently used “legacy” measures such as the SF–36 and EQ–5D. (44) Range of Motion (ROM): of the shoulder is an objective measure of shoulder function. A blinded examiner will measure the range of motion in forward elevation, external rotation in the neutral position external rotation with the arm in abduction, internal rotation in the neutral position, and internal rotation with the arm in abduction. A goniometer will be used measuring to the nearest degree. The range of motion for forward elevation will range between 0–180 degrees with a higher number indicating a better outcome. External and internal rotation ranges from 0–90 degrees with a higher number indicating a better outcome.

Despite these concerns, studies demonstrating immobilization type/length and precisely defined physiotherapy progression criteria are limited to expert opinion. As a consequence, conservative postoperative rehabilitation orthodoxy has recently been challenged by a select few. (6,7,10,20,21) These outliers adopted an accelerated rehabilitation approach, shortening post-surgical immobilization to a minimum of two weeks rather than the "agreed-upon" expert recommendation of four to six weeks.
Coupled with early initiation of range of motion (ROM) training, their protocol sought to optimize and restore shoulder mobility, eliminate postoperative joint capsule adhesions, and scarring between muscle groups; complications commonly associated with prolonged and restricted shoulder immobilization. {…} (22,23) These foreword thinking physicians recognized patients exceeding previously established human boundaries if given a chance. Nevertheless, one must question: What is truly possible? Are we creating fictional limitations? Barriers that prevent patients from pushing beyond their limits? To date, we are not aware of any literature describing immediate active shoulder rehabilitation (IASR) training without the utilization of a protective immobilizer, (16,24,25) abduction pillow, (26)(27)(28)(29) sling, (5)(6)(7)9,10,21,(30)(31)(32) or "simple sling" (20,(33)(34)(35)(36)(37)(38) following rTSA. Therefore, the purpose of this randomized controlled pilot study was to evaluate and compare the IASR protocol to current institutional outpatient controls. We hypothesize that the IASR will offer an accelerated return to independence, superior post-operative patient-reported out measures (PROMs), shoulder ROM, and patient satisfaction. Further, the IASR protocol will quantitatively demonstrate a reduction in the number of formal rehabilitation visits. Equating to enhanced costeffectiveness and overall value compared to control. Hypothesis: The IASR protocol will result in superior ASES, SST, PROMIS Global-10, and shoulder ROM scores at 1-year follow-up compared to control.

Objectives {7}
Rationale: Patients in the accelerated rehabilitation protocol group will regain ROM and strength at a faster pace than those in the rehabilitation control group.
Objective 2: To determine the safety and outcome differences of the IASR protocol compared to the control by assessing the subscapularis tear rate, prosthesis dislocation, and hardware failure at 1-year follow-up with radiographic and ultrasound analysis.
Hypothesis: Patients in both groups will have similar subscapularis tear, prosthesis dislocation, and hardware failure rates. However, patients with identifiable subscapularis tears will report lower functional outcomes scores coupled with inferior ROM.
Rationale: A current relationship between postoperative subscapularis tears and rehabilitation outcome measures post rTSA is unknown.
Objective 3:To evaluate the cost-effectiveness and overall value of implementing the IASR protocol compared to control.

Hypothesis:
The IASR protocol will quantitively reduce formal rehabilitation and physical therapy (PT) visits. Thus, implementation will demonstrate superior cost-savings and overall value compared to control.
Rationale: In today's medical landscape, healthcare providers, insurance companies, and patients are continually looking for faster, safer, and cheaper healthcare and surgical alternatives.
Outcomes (Table 1) will be assessed at baseline, 2, 6, 12, 26, and 52 weeks post-surgery with the 52-week assessment serving as the principal outcome assessor. The study protocol was developed based off and adhered to the Standard Protocol Items: Capable of completing self-administered questionnaires.
Be willing and able to return for all study-related follow-up procedures.
Able and willing to give informed consent. Proficient in the English language.
Exclusion Criteria:Any patients who meet any of the following criteria will not be included in this study.
In-Clinic, the patient cannot have/be: Been treated with a primary rTSA for proximal humeral fracture.
An active bacterial infection of the shoulder.
Additional ipsilateral or contralateral upper limb pathology, not including the shoulder, which requires active treatment (i.e., surgery or brace). Taken anticoagulants within ten days prior to surgery.
Peripheral neuropathy or other neurological disorders that may impair their ability to ambulate.
On worker's compensation.
Any condition requiring chemotherapy.
Active tobacco user or former tobacco user who is not free of using tobacco for eight weeks.
A current drug or alcohol abuser.
A major medical illness. (life expectancy less than two years or unacceptably high operative risk) Suspicion of cervical radiculopathy or myelopathy.
Deltoid insufficiency on physical examination. Intra-operative, the patient cannot have/be: An iatrogenic glenoid fracture.
Post-operative, the patient cannot have/be: A neurological injury of the upper extremity.
If a patient is a surgical candidate for a primary rTSA, their surgeon will evaluate him/her to determine if they are eligible for inclusion in this study. If the patient fulfills the eligibility criteria, they will be referred to the principal investigator.
Who will take informed consent? {26a} The principal investigator performs the final eligibility assessment, provide the patient with study specifics, and ask for consent to participate. It will be made clear that by agreeing to take part in the study, the patient will be advised to follow the postoperative physical rehabilitation protocol they were randomized to. The patient is further informed that they can refuse to participate in the study and/or wish to withdraw from the study at any time. After the patient has their questions answered and has been consented, following ample time to decide, the patient and the study staff with whom the informed consent was discussed will sign and date the informed consent form.
The study participant will be queried on the intent of the study and follow-up time points to assess their understanding of the consent. A copy will be provided to the study patient for future reference. The patient will be considered enrolled in the study and will be randomly assigned to one of the two postoperative physical rehabilitation protocols following a randomization scheme produced by a random number generator. Neither the patient nor the physician will be blinded to the intervention. If the patient does not consent to the study, they will receive appropriate treatment as determined by the

Intervention description {11a}
All rTSA will be performed and admitted as an inpatient procedure by a non-blinded, dualfellowship (Shoulder and Elbow, Sports Medicine) trained orthopaedic surgeon with 14 years of experience in this field. A deltopectoral approach will be employed. The biceps tendon will be tenotomized, and the circumflex vessels will be cauterized or ligated. Next, the humeral head will be dislocated and the rotator cuff will be inspected for tears. The humeral head will then be reamed up to size for the humeral broach and final component cortical contact. A cutting jig will be placed and the humeral head removed using an oscillating saw with the cut at 30 degrees retroversion at the level of the insertion of the rotator cuff. Broaching of the humeral canal will then take place to size the broach and final humeral stem implant appropriately. Exposure of the glenoid by retraction of the humerus and capsulectomy and labrectomy then will be completed. A guide pin will be inserted in the glenoid in 10 degrees of cephalic tilt and the glenoid reamed to a 3 O'clock to 9 O'clock subcortical ream. A single implant system (Comprehensive Reverse Shoulder System; Zimmer Biomet, Warsaw, Ind, USA) will be used for all study patients.
A 25 mm glenosphere base plate will be inserted and secured with a 6.5 mm center screw and 4 peripheral screws of both locking and cortical design. A glensosphere of 36 or 41 mm will be selected based on patient anatomy and inserted with a taper fit locking mechanism to the glenosphere base plate. The trial broach will be removed and repair stitches placed around the subscapularis osteotomy site. The final size-matched stem will be inserted in 30 degrees of retroversion followed by component trialing conducted. A tray/polyethylene combination that provides appropriate soft tissue tension and range of motion will be selected and assembled. These final components will be inserted onto the stem and the construct reduced. Subsequent osteotomy repair and biceps tenodesis to the upper pectoralis will be conducted.
A non-blinded, inpatient PT evaluation is scheduled for all patient's post-op day 1.
Randomization grouping is revealed to the patient at that time. Patients are appropriately educated on exercise execution and restrictions unique to their rehabilitation group and instructed to follow said protocol regimen. Patients are given supporting documentation specific to their rehabilitation grouping that details individual exercise descriptions and frequencies to complete on a temporal basis. Criteria for discontinuing or modifying allocated interventions {11b} Deviations will be documented using our standardized protocol deviation form, and the protocol deviation log will be updated. The protocol deviation form is signed by the coordinator documenting the deviation and the PI or research manager. At that time, a determination of subject status will be made-continue to follow, use data already collected, withdraw, lost to follow-up. Finally, the study may be stopped early by the investigator or the FDA for any of the following reasons: For the patients' safety If the patient does not follow the instructions for the study Hardware loosening

Strategies to improve adherence to interventions {11c}
The TRIA research team will facilitate protocol intervention adherence. Through a multifaceted collaborative effort, the research team developed the protocol, study delivery system, operating procedures, training, survey database, and patient report forms. Further, to ensure home therapy compliance, patients will receive a daily text message alert from a HealthPartners text reminding service.

Relevant concomitant care permitted or prohibited during the trial {11d}
Physical therapy may occur in off-site clinics and centers. However, we would prefer if patients received their physical therapy at a TRIA/HealthPartners location conveniently located close to the patients' residence.

Provisions for post-trial care {30}
If a patient gets hurt and/or sick from being in this study, they are instructed to seek medical treatment and inform the investigator as soon as possible. TRIA will bill the patient's insurance, if applicable, and the patient will be responsible for their usual copay or deductible. If the patient has Medicare, TRIA will facilitate the delivery of patient information that identifies said patient to the Medicare system. If a patient does not have insurance or if their insurance does not cover their treatment, TRIA will bill the patient for the costs of the treatment.

Outcomes {12}
American Shoulder and Elbow Score (ASES): The ASES is a standardized form used for the assessment and evaluation of patient shoulder function. Patients evaluate pain, instability, and their activities of daily living. Physicians record demographic details, ROM measurements, specific physical signs, stability, and strength scores. The ASES score validity, reliability, and responsiveness has been assessed in a variety of shoulder problems including rotator cuff disease, glenohumeral arthritis, shoulder instability, and shoulder arthroplasty. (41,42) The assessment consists of 11 items, one item for pain and 10 items for function. The score for each subscale is out of 50 (0-50), with a higher score indicating a better outcome. The total score is a sum of both subscales, ranging between 0-100, using the following formula, Total score = ((10 − VAS pain) × 5) + (5/3 × sum of function items).

Simple Shoulder Test (SST):
The SST is a series of 12 "yes" or "no" questions the patient answers about the function of the involved shoulder. The answers to these questions provide a standardized way of recording the function of a shoulder before and after treatment. (43) There are 2 items on function related to pain, 7 items about functions/strength and 3 items about range of motion. There are no subscales. A "yes" response is 1 point and a "no" response is 0 point. The following formula is used to calculate a score out of 100 (0-100), total = number of "yes" items/number of completed items × 100 = % "yes" responses. A higher score indicates better function from a scale of 0-100.
PROMIS Global-10: The PROMIS Global-10 is a publicly available global health assessment tool that allows measurements of symptoms, functioning, and healthcare-related quality of life (HRQoL) for a wide variety of chronic diseases and conditions. The PROMIS Global-10 short form consists of 10 items that assess general domains of health and functioning, including overall physical health, mental health, social health, pain, fatigue, and overall perceived quality of life. 7 questions inquire about health in "general," and 3 questions assess emotional problems, fatigue and pain in the last 7 days. Raw subscale scores for physical and mental health each are calculated out of 20. The raw score are converted to T scores for physical and mental health using the following formulas: the Global Physical Health score is generated by summing responses to Global03, Global06, Global07rescored, and Global08rescored. The Global Mental Health score is generated by summing responses to Global02, Global04, Global05, and Global10rescored. T scores range from 0-100. A high score represents a better outcome. There is not a total score for this tool. The 10 questions of the Global-10 have primarily been adapted from other frequently used "legacy" measures such as the SF-36 and EQ-5D. (44) Range of Motion (ROM): of the shoulder is an objective measure of shoulder function. A blinded examiner will measure the range of motion in forward elevation, external rotation in the neutral position external rotation with the arm in abduction, internal rotation in the neutral position, and internal rotation with the arm in abduction. A goniometer will be used measuring to the nearest degree. The range of motion for forward elevation will range between 0-180 degrees with a higher number indicating a better outcome. External and internal rotation ranges from 0-90 degrees with a higher number indicating a better outcome.
Radiographic (X-Ray) Measures: A musculoskeletal radiologist and dual-fellowship trained orthopaedic surgeon will evaluate anteroposterior, axillary, and scapular-y view radiographs. The prosthesis review will adopt the rTSA radiographic assessment checklist Shoulder Ultrasound: All ultrasonograms will be obtained in real-time with use of an ATL HDI 3000 scanner (Advanced Technologies Laboratories, Bothell, WA) or a Siemens Elegra scanner (Siemens Medical Systems, Issaquah, WA), and a variable high-frequency lineararray transducer (7.5 to ten megahertz) to assess subscapularis integrity. All patients will have standardized bilateral ultrasonography of the shoulder, performed by one of two radiologists who experienced with the technique. (51,52) A finding of a full-thickness rotator cuff tear will be recorded when the rotator cuff cannot be visualized due to either a complete cuff avulsion and retraction under the acromion or a focal defect in the cuff created by a variable degree of retraction of the torn tendon ends. If a rotator cuff tear is not visualized, the deltoid muscle will be compressed against the cuff with the transducer to separate the torn tendon ends at the site of a non-retracted tear. A finding of a partial-thickness tear is present if minimal flattening of the bursal side of the rotator cuff (a bursal-side partial-thickness tear) or a distinct hypoechoic or mixed hyperechoic and hypoechoic defect visualized in both the longitudinal and the transverse plane at the deep articular side of the rotator cuff (an articular-side partial-thickness tear).
The extent of the rotator cuff tear will be determined with transverse measurements. Both radiologists will report the ultrasound, regardless of who performs it.
Cost of Care Measures: Number of PT visits.
Cost of PT visits to the patient calculated as mentioned below: Request a list of all patients that had an rTSA and rehab at TRIA. At a per-patient level, we will see the number of visits and cost per PT session. Then take the total cost/total number of sessions to get an average. Total Cost of PT = Average cost per session x Number of PT visits Participant timeline {13} Table 2 shows the expected flow of participants through recruitment, assessment, intervention, and follow-up. The patient will have to attend a total of six visits. In all these visits the patient will be asked to complete questionnaires, undergo a shoulder examination, and x-rays. An additional shoulder ultrasound will be conducted at the last visit.
The study is expected to take up to 30 months, consisting of 20 months for recruitment and randomization, 8 months for final participant follow-up, and 2 months for analysis and manuscript writing. All staff listed on the study and participating in the research will attend a study kick-off meeting where the details of the study will be discussed. A review of the protocol, consent form, delegation of duties, case report forms and study procedures will be reviewed. All staff on the study have been trained by research staff and investigators on proper consent procedures and have completed CITI training.

Assignment of intervention: allocation
Sequence generation {16a} 1:1 for treatment to control. Randomization will be conducted during the initial evaluation after consent has been confirmed via block randomization and delivered through computerized slips. A random number generator will produce the randomization assignment and scheme.

Concealment mechanism {16b}
A senior non-blinded, research manager will be responsible for preparing the randomization scheme and inform the operating surgeon prior to each patient's designated surgery day.

Implementation {16c}
If a patient is a surgical candidate for a primary rTSA, their surgeon will evaluate him/her to determine if they are eligible for inclusion in this study. If the patient fulfills the eligibility criteria, they will be referred to the principal investigator. The principal investigator performs the final eligibility assessment, provide the patient with study specifics, and ask for consent to participate.
A senior non-blinded, research manager will be responsible for preparing the randomization scheme and inform the operating surgeon prior to each patient's designated surgery day. All assessors and study personnel other than the senior research manager and operating surgeon are blinded to group allocation. Patients are instructed not to communicate their group allocation to the study staff or other participating patients. All data assessed will be processed and analyzed by an institutional statistician blinded to treatment group allocation.

Assignment of interventions: Blinding
Who will be blinded {17a} All assessors and study personnel other than the senior research manager and operating surgeon are blinded to group allocation. Patients are instructed not to communicate their group allocation to the study staff or other participating patients. All data assessed will be processed and analyzed by an institutional statistician blinded to treatment group allocation.

Procedure for unblinding if needed {17b}
Data collection and management

Plans for assessment and collection of outcomes {18a}
Data collected from the follow-up will be answers to the functional shoulder (ASES, SST, and ROM), quality of life questionnaires (PROMIS Global-10), and imaging impressions at the time of consent (baseline), 2, 6, 12, 26, and 52 weeks post-surgery. If the patient misses the follow-up time points, we will consider data from 2 weeks ± 2 days as 2-week data, 6 weeks ± 1 week to be 6-week data, 12 weeks ± 2 weeks to be 12-week data, 26 weeks ± 3 weeks to be 26-week data, and 52 week ± 4 weeks to be 52-week data.

Plans to promote participant retention and complete follow-up {18b}
If the patient misses one of the follow-up visits or does not come in during the timeframes specified above, we will continue to collect data from the rest of the time points unless the patient no longer wishes to participate or the principal investigator terminates their study participation.

Data management {19}
The research coordinator, or delegate, will complete a chart audit form for all patients and enter all patient data into an electronic database that only the study personnel have access to. Each study participant will be identified by their assigned study subject number in an electronic database. The research coordinator will keep the password-protected cross-walk files linking the participant names and medical record numbers to their subject number. Each study subject will have their own binder that includes all case report forms and their signed consent form. Patient binders and any other paper forms related to the study will be stored in a locked file cabinet in the research department at TRIA.

Confidentiality {27}
This study is being conducted in accordance with the ethical principles that are consistent with the International Conference of Harmonisation (ICH) and good clinical practice (GCP) guidelines. All study staff are fully trained on the elements of patient privacy, HIPAA, and confidentiality. All data points collected will be reviewed to ensure values are within an acceptable range. Subjects will be selected at random to ensure case report forms match electronic databases. Data will be maintained per organizational policy.
No copies of consent forms will be placed in the subject's medical, employment, or educational records. The subject will be associated with the research study in the medical record, and a flag added to their account to alert other medical staff as to their participation in the study.
Paper-based records will be kept in a secure location and only be accessible to personnel involved in the study. Computer-based files will only be made available to personnel involved in the study through the use of access privileges, passwords, and encryption.
Prior to access to any study-related information, personnel will be required to sign statements agreeing to protect the security and confidentiality of identifiable information.
Whenever feasible, identifiers will be removed from study-related information. Precautions are in place to ensure electronic data is secure by using passwords and encryption. A number will code data that only the investigators or research staff will have access to. All staff will be trained in the collection of data, and training will be documented and stored in the site regulatory binder.
Monitoring will be conducted to assure the rights and safety of participants, confirm the study conduct follows the guidelines of good clinical practice, assure maintenance of required documents, verify adherence to the protocol, monitor the quality of data collected, and assure accurate reporting and documentation of all adverse events.
Monitoring will ensure all forms are completed. Internal monitoring will be completed on all investigator-initiated studies on a routine basis as determined departmental leadership. Findings will be regularly reported in summary format to the investigator and study team.
The senior research manager and PI or Institute Medical Director will monitor safety for this study. The research manager will routinely monitor protocol deviations. The PI or Institute Medical Director will provide oversight and review of any adverse events.
No data will be shared with external entities. Identifiers will be removed prior to statistical analysis and will be permanently deleted from the TRIA network upon publication of the results. If there is a violation of patient privacy, measures will be taken to inform the patient and to decrease the risk of further loss of privacy.
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33} Not applicable Statistical methods

Statistical methods for primary and secondary outcomes {20a}
Primary Outcome: The responder rate of the IASR group is compared to the responder rate of the control group. A patient is considered a responder if they achieve a clinically significant improvement of at least 13.6 ± 2.2 points in the ASES, 1.5 ± 0.3 points in the SST scores at postoperative 1-year compared to baseline. (55,56) Supporting Efficacy Endpoints: In addition to the primary outcome, the responder status to the PROMIS Global-10 will be calculated.
Secondary Endpoints:A comparison between the IASR and control rehabilitation groups will be made using a two-sided independent students t-test with an alpha = 0.05 Rate of a subscapularis tear.
Rate of prosthesis dislocation.
Rate of Hardware failure.
Rate of scapular notching.
The number of total PT visits.

Interim analyses {21b}
Two interim analyses will be performed, one at 26 and 52 weeks, so we use the Bonferroni correction to adjust the significance level for these additional tests will be utilized.
Methods for additional analyses (e.g., subgroup analyses) {20b} A descriptive statistical analysis will include all counts percentages and confidence intervals for group differences in percentages. Covariate analysis of the SST score and PROMIS Global-10 will be conducted using age, gender, BMI, tobacco use, rate of subscapularis tear, prosthesis dislocation, hardware failure, scapular notching, and the number of total PT visits.
Descriptive summaries of the patient and operative information will be generated. Means and SD will be reported for normally distributed continuous variables, medians, and ranges for non-normally distributed continuous variables; and frequencies and percentages for categorical variables. Age, symptom duration (in months), number of previous surgeries, number of comorbid conditions, BMI, and surgery duration using a 2sample t-test or the Mann-Whitney-Wilcoxon test if normality assumptions are not met.
These patients will also be compared on gender, race/ethnicity, employment, worker's compensation status, dominant hand, and smoking status using a chi-square test.
Similarly, patients who drop out of the study (i.e., have baseline information only) will be compared to patients who do not drop out on the same variables using the same tests as those stated above. A generalized chi-square test will be used to evaluate differences in the number of patients responding in each category to each preoperative expectation.
To address the primary objective, changes in scores on the quality of life measure from baseline to follow-up will be compared between the two groups using a 2-sample t-test. If the change scores are not normally distributed, we will use the Mann-Whitney-Wilcoxon test instead.
To address the primary objective, the ASES score, Simple Shoulder test score, and PROMIS Global-10 scores, changes in scores from baseline to follow-up will be compared between the two groups using a 2-sample t-test. If the change scores are not normally distributed, we will use the Mann-Whitney-Wilcoxon test instead.
To address the incidence of retear, prosthesis dislocation, and hardware failure (secondary objective 2), we will use a chi-square test to compare the number of patients in each group that had a retear confirmed by ultrasound at 12 months. To gain more information, logistic regression will be employed with retear (yes/no) as the response and any demographic or clinical variables that differ significantly between groups as predictors.
To address the tertiary objective, changes in the number of PT visits and total cost of PT (number of PT visits x average cost of a PT visit) from baseline to follow-up will be compared between the two groups using a 2-sample t-test. If the change scores are not normally distributed, we will use the Mann-Whitney-Wilcoxon test instead.
Statistical analyses will be conducted with IBM-SPSS 22.0 software (IBM-SPSS, Chicago, IL). In all tests, a statistical significance of p < 0.05 will be considered. The Kolmogorov-Smirnov test will determine normality. For comparison between groups, the unpaired Student t-test or nonparametric Mann-Whitney U test will be used for continuous variables, and the x2 test, Fisher exact test, or Mantel-Haenszel test for categorical variables. For comparison between preoperative and postoperative data and different postoperative periods within a group, the paired t-test or Wilcoxon signed-rank test will be used.
All tests will be two-sided, and a significance level of α = 0.0167 will be used throughout.
Two interim analyses will be performed, one at 26 and 52 weeks, so we use the Bonferroni correction to adjust the significance level for these additional tests will be utilized. That is, α = 0.05/3 = 0.0167.) Methods in analysis to handle protocol non-adherence and any statistical method to handle missing data {20c} Monitoring will be conducted to assure the quality of data collected, and assure accurate reporting and documentation of all adverse events. Monitoring will ensure all forms are completed and data entry is valid.Missing data will be assessed and determination of the subject status will be made-continue to follow, use data already collected, withdraw, or designate lost to follow-up.
Plans to give access to the full protocol, participant level-data and statistical code {31c} No data will be shared with external entities. Identifiers will be removed prior to statistical analysis and will be permanently deleted from the TRIA network upon publication of the results. If there is a violation of patient privacy, measures will be taken to inform the patient and to decrease the risk of further loss of privacy.
Oversight and monitoring All staff listed on the study and participating in the research will attend a study kick-off meeting where the details of the study will be discussed. A review of the protocol, consent form, delegation of duties, case report forms and study procedures will be reviewed. All staff on the study have been trained by research staff and investigators on proper consent procedures and have completed CITI training.
The study proposal was approved at TRIA's monthly research meeting and reviewed by the scientific review committee. The feedback from the scientific review committee was used to make changes to the protocol to ensure appropriateness in the research methodology and delivery.
This study proposal meets our organizational goals in improving healthcare and focusing on rehabilitation from a joint replacement procedure to bring value to the individual patient and decrease cost, simultaneously.
Composition of the data monitoring committee, its role and reporting structure {21a} The investigators of this study will abide by the study protocol, all applicable laws and federal regulations, and criteria set by the reviewing IRB. A study kick-off meeting will be held prior to the commencement of the study to orient the investigators and study staff. The DSMB for this study is the TRIA Institute Board of directors and is responsible for: Review of the research protocol informed consent documents and plans for data safety and monitoring; Evaluate the progress of the trial; Protect the safety of the study participants (review of adverse events); Report on the safety and progress of the trial; Make recommendations to the sponsor, PI, and, if required, to the Food and Drug Administration (FDA) and the IRB concerning continuation, termination or other modifications of the trial based on the observed beneficial or adverse effects of the treatment under study; and Ensure the confidentiality of the trial data and the results of monitoring.
Any findings (such as protocol violations, significant safety concerns) will be promptly submitted to the IRB (and sponsor).

Adverse event reporting and harms {22}
An adverse event is any untoward medical occurrence in a study patient administered a study treatment, regardless of whether a causal relationship exists between the medical occurrence and the study treatment. An adverse event, therefore, is any unfavorable and unintended sign, symptom, abnormal assessment, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Adverse events will be collected and recorded on the appropriate case report form until the patient participation is complete at the 1-year postoperative time point. Adverse events may be noted subjectively from the patient or objectively during the follow-up visits. Adverse events will be categorized (Table 3) based on the severity (mild, moderate, or severe), serious adverse events, or unexpected adverse events. Severe Signs/symptoms that make the patient disabled from work or routine activities.

Serious
Signs/symptoms that is life-threatening requires hospital admission, prolonging existing hospitaliz death.

Unexpected
That is not defined under mild, moderate, severe, and serious adverse events.

Risk Analysis
Risks of this study focus on the period after the surgery, since study intervention will occur postoperatively. The standard of care will be provided from the initial recruitment visit until the patient is discharged from the surgery.
The following risks are anticipated from the study generally: Radiation exposure for all radiographic films.
The following risks are anticipated from early shoulder activity and motion post rTSA: Loosening of hardware.
The questionnaires used in the study may make the participants uncomfortable or upset.
Participants will have the option not to answer any questions that make them uncomfortable and are free to stop a survey at any time. Investigators have chosen validated outcome tools for use in the study.
X-rays involved increase exposure to radiation. The total radiation in a knee x-ray is 0.01 mSv (Milli Sieverts). The average person is exposed to about 3.0 mSv of radiation per year from natural sources (naturally occurring radioactive materials and outer space). The radiation from a knee x-ray is equal to about 1.5 extra days of average exposure.
Physical performance testing: There are minimal risks associated with physical performance testing. Possible risks may include muscle fatigue, muscle or joint soreness, and in rare instances, muscle strain. To minimize physical risks, testing will be conducted under the direct supervision of a trained medical professional.
To minimize and protect the study subjects from anticipated risks mentioned, they will be counseled and instructed to contact the research study staff if they experience the above mentioned potential risk.

Frequency and plans for auditing trial conduct {23}
The research coordinator, or delegate, will complete the chart audit form for all patients and enter all the data into an electronic database that only the study personnel have access to. In the database, each study participant will be identified by their assigned study ID number. The research coordinator will keep the password-protected cross-walk file linking the participant names and MRNs to their study ID numbers. Each study subject will have their own binder that includes all case report forms and their signed consent form. These patient binders and any other paper forms related to the study will be stored in a locked file cabinet in the research department at TRIA.
Plans for communicating important protocol amendments to relevant parties (e.g., trial participants, ethical committees) {25} Protocol amendments associated with trial safety, scientific aspects of the study, and any emerging evidence as it relates to the trial will be directly communicated to the HealthPartners IRB, DSMB, TRIA research team, and trial participants.

Dissemination plans {31a}
Irrespective of the IASR trial outcome, the results will be submitted for publication in an appropriate journal. An abstract will be developed and submitted to appropriate shoulder conferences by the principal investigator. Subsequently, the principal investigator will be responsible for manuscript composition, which the co-investigators will review and approve prior to submission. The principal investigator must approve subsequent studies utilizing data obtained from the IASR trial. The results of our study will be incorporated into our practice and replace traditional physical therapy protocols.

Discussion
Reverse shoulder arthroplasty is an established and reliable surgical procedure that relieves pain and function. However, despite the procedural success, disagreement and controversy exist regarding the principle components and concepts of postoperative rTSA rehabilitation. While adequate postoperative protection and motion restriction during rehabilitation following aTSA was found essential, (57)  The IASR trial protocol will be the first randomized trial to compare the effectiveness of an accelerated shoulder rehabilitation program following rTSA compared to a traditional rehabilitation protocol adopted by our institution. (9,18) It will address the lack of randomized trials assessing post-surgical and functional outcomes by providing objective, scientifically based results, and information. Information that will be essential in determining the best practice that optimizes patient functional outcomes, satisfaction, and cost-effectiveness post rTSA.
The IASR protocol study is strengthened by utilizing a single surgeon with 14 years of experience performing a high volume of primary rTSA cases annually. Additionally, the surgeon, who also serves as our primary investigator (PI) has completed research studies, including trials with a high recruitment rate. Finally, the PI has a fully staffed research department with 10 years of experience at their disposal.
Our protocol, however, is not without limitation. Unfortunately, we are unable to blind the PI and patient; thus, the risk for confirmation bias and the Hawthorne effect cannot be eliminated, respectively. Additionally, we cannot guarantee absolute compliance with home self-directed physical therapy. To aid in patient compliance, our research department will remind study subjects via text message every morning to perform their designated home therapy protocol through our Institutional text messaging service.