Participants, interventions and outcomes
Study setting {9}
Patients will be recruited from a single site (TRIA Orthopaedic Center, Bloomington, MN) neighboring the fourteenth largest US metropolitan area. (40) Patients will be considered for enrollment in the study if they meet all of the inclusion criteria and none of the exclusion criteria. The criteria are based on clinical (history and physical examination), intraoperative, and postoperative findings. Patients who meet the clinical inclusion and exclusion criteria will be enrolled provisionally until the surgery has been performed. Information pertaining to the study site location can be found at: URL:https://clinicaltrials.gov/ct2/show/NCT03804853?cond = reverse+total+shoulder+arthroplasty&draw = 1&rank = 5
Eligibility criteria {10}
Inclusion criteria: Any patient who meets all of the following criteria may be included in this study. The patient must be:
- > 55 years of age.
- Candidate for a primary rTSA. (CPT code 23472)
- 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.
- A surgical history including ipsilateral aTSA, rTSA, hemiarthroplasty, or instability repair.
- 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.
- Complications from Primary rTSA (i.e., postoperative infection, bleeding, hardware failure).
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 surgeon.
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Not applicable
Interventions
Explanation for the choice of comparators {6b}
The comparator arms (Figure 1) are an accelerated rehabilitation (IASR) strategy versus standardized care following rTSA (CPT: 23472). Outcomes 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.
Intervention description {11a}
All rTSA will be performed and admitted as an inpatient procedure by a non-blinded, dual-fellowship (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.
IASR Protocol (Additional file 1): The IASR is a single-phase 6-week protocol that adheres to home rehabilitation. Patients begin immediate pendulum swings, seated scapular retraction exercises, four-quadrant-stretching, seated or standing table slides, and full aROM of the shoulder, hand, wrist, and elbow post-op day 1 in the hospital. Immediate pROM and aROM is unlimited within pain-free ranges. Patients are instructed that sling immobilization is not necessary. However, a sling can be used as needed for pain control. Protocol endpoint goals include achieving >120 degrees of passive flexion, > 45 degrees of passive external rotation (at side), active standing flexion to > 100 degrees with minimal compensation, a resting pain-free state, and restoring functional use of involved extremity for all required activities of daily living including return to work when cleared by surgeon.
Standardized Protocol (Additional file 2):The standardized TRIA physical therapy protocol follows a traditional two-phase approach. (9,18) Patients begin therapy followed by a gradual return to aROM of the shoulder beginning at post-op week 6, calling for 18 total physical therapy visits over 12 weeks. Therapy will transition from two sessions per week in Phase I (0–6 weeks) to one session per week in Phase II (6–12 weeks).
- Phase 1 (0–6 weeks): Patients are instructed to wear a sling at all times for four weeks, except for dressing changes, hygiene, and formal therapy. Motion restrictions and precautions include aROM, internal rotation, internal isometric rotation, internal rotation progressive resistive exercises (PREs), shoulder extension with adduction and internal rotation, and shoulder hyperextension. Patients, however, are permitted to begin pROM as tolerated prohibiting internal rotation in the scapular plane, aROM of the elbow wrist and hand, pendulum swings, submaximal scapular exercises (retraction, depression, circles) and submaximal pain-free deltoid isometrics.
- Phase 1 Goals: To maximize surgical repair protection, maintain mobility of the surrounding joints, and control swelling and pain.
- Phase 2 (6–12 weeks): Patients begin a progressive sit to stand active assistive ROM (aaROM) and aROM in all planes, and progressive rhythmic scapular and glenohumeral stabilization exercises. Post-op week 10 introduces isometric to isotonic progression of external and internal rotation, and PREs in all planes within ROM restrictions; emphasizing the deltoid.
- Phase 2 Goals: To achieve 80–120 degrees of elevation, 30 degrees of external rotation, and to restore the functional use of the involved extremity for all required activities of daily living, including return to work when cleared by the surgeon.
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 published by Roberts et al. (45) Scapular notching will be evaluated according to the Sirveaux classification. (46) Humeral radiolucent lines will be classified according to the Sperling System. (47,48) The inferior overhang of the glenosphere will be measured according to Bigorre et al. (49) And implant loosening will adhere to the principles published by Melis et al. (50)
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 linear-array 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
Sample Size {14}
The calculation was based on postoperative ASES scores in a previously published comparative study. (53) To detect a clinically ASES score relevant difference of 15.8 between groups, with a mean improvement standard deviation (SD) of 20.6, alpha of 5% and power of 80%, 31 patients were needed in each group. Assuming a drop-out rate of 20%, at least 37 patients were required per group. This leaves us with a total sample size of 74. If we consider the minimal clinical important difference (MCID) of 11.4 for SST, we would need 34 patients per group to possibly reach statistical significance. (54) A total of 34 patients will be necessary to detect a 10°difference in ROM of the shoulder in all planes based on an SD of 10°. (55)
Recruitment {15}
TRIA Orthopaedic Center is the ideal location for patient recruitment as Dr. Walsh performs approximately 100 anatomical and reverse total shoulder arthroplasty procedures (75%).
The research branch of the TRIA Institute is comprised of a Medical Director, Research Manager, 2 full-time Research Coordinators, a Research Assistant, a Research Fellow, a Ph.D. Research Scientist and an MD Research Scientist. The Research Coordinators and Assistant are primarily involved in the day to day research activities. All can take on the work of an additional study.
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}
Not applicable
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 2-sample 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
Composition of the coordinating center and trial steering committee {5d}
The research branch of the TRIA Institute is comprised of a Medical Director, Research Manager, 2 full-time Research Coordinators, a Research Assistant, a Research Fellow, a Ph.D. Research Scientist and an MD Research Scientist. The Research Coordinators and Assistant are primarily involved in the day to day research activities. All have the capacity to take on the work of an additional study.
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 Data Safety Monitoring Board (DSMB) will evaluate the safety of the study. The DSMB may consider stopping the study if there is evidence of study related death, upper limb neurovascular injury, high rate of secondary surgery, deep vein thrombosis with a pulmonary embolism.
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.
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.
- Peri-prosthetic bone fracture.
- Hematoma formation.
- Wound dehiscence.
- Prosthesis dislocation.
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.