Hip Fracture Evaluation With Alternatives of Total Hip Arthroplasty Versus Hemi-Arthroplasty: A Multi-Centre Randomized Trial Comparing Total Hip Arthroplasty and Hemi-Arthroplasty on Secondary Procedures and Quality of Life in Patients With Displaced Femoral Neck Fractures
Phase: NA
Conditions: Hip Fractures, Femoral Neck Fractures
Sponsor: McMaster University

 
 
Comparing Total Hip Arthroplasty and Hemi-Arthroplasty 
on Secondary Procedures and Quality of Life in Adults With 
Displaced Hip Fractures 
 
NCT00556842 
 
Study Protocol 
 
Prepared on: January 30, 2014 
 
 

 
 
 
 
 
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HEALTH Protocol, Version 10.0 
 
30 January 2014  
 
 
Hip Fracture Evaluation with ALternatives of Total Hip  
Arthroplasty versus Hemi-Arthroplasty (HEALTH): 
 
 
A Multi-Centre Randomized Trial Comparing Total Hip Arthroplasty and  
Hemi-Arthroplasty on Secondary Procedures and Quality of Life in Patients with  
Displaced Femoral Neck Fractures 
 
 
 
 
Prepared by:  
 
Mohit Bhandari and Gordon Guyatt  
 
 
 
                         
 
 
 
The HEALTH study protocol is the confidential intellectual property of  
the HEALTH Steering Committee and McMaster University. 
 
 

 
 
 
 
 
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Table of Contents 
 
LIST OF TABLES .......................................................................................................................... 4 
LIST OF FIGURES ........................................................................................................................ 5 
LIST OF ABBREVIATIONS ......................................................................................................... 6 
STUDY SUMMARY...................................................................................................................... 7 
1. INTRODUCTION ...................................................................................................................... 8 
1. INTRODUCTION ...................................................................................................................... 8 
1.1 Background ........................................................................................................................... 8 
1.2 Hemi-Arthroplasty ................................................................................................................ 9 
1.3 Total Hip Arthroplasty .......................................................................................................... 9 
1.4 Surgical Management of Hip Fractures – Uncertainty and Controversy .............................. 9 
1.5 Alternative Operative Management Strategies in Femoral Neck Fractures – Direct 
Comparisons for Randomized Trials .......................................................................................... 9 
1.6 Hemi-Arthroplasty versus Total Hip Arthroplasty – Indirect Comparisons from Meta-
Analyses .................................................................................................................................... 10 
2. STUDY OBJECTIVES ............................................................................................................. 10 
2.1 Primary Objective ............................................................................................................... 10 
2.2 Secondary Objectives.......................................................................................................... 10 
3. STUDY DESIGN...................................................................................................................... 11 
3.1 Study Overview .................................................................................................................. 11 
3.1.1 Expertise-Based Randomized Controlled Trial ........................................................... 11 
3.2 Proposed Primary and Secondary Outcome Measures ....................................................... 12 
3.2.1 Primary Outcomes ....................................................................................................... 12 
3.2.2 Secondary Outcomes ................................................................................................... 13 
4. SUBJECT SELECTION AND RISK ....................................................................................... 14 
4.1 Inclusion and Exclusion Criteria ......................................................................................... 14 
4.1.2 Exclusion Criteria ........................................................................................................ 15 
5. STUDY INTERVENTIONS .................................................................................................... 15 
5.1 Arthroplasty Procedures...................................................................................................... 15 
5.1.1 Total Hip Arthroplasty ................................................................................................. 15 
5.1.2 Hemi-Arthroplasty ....................................................................................................... 15 
5.2 Standardization of Procedures and Peri-Operative Care .................................................... 16 
5.2.1 Threshold Performance for Expertise in Total Hip Arthroplasty and Hemi-
Arthroplasty .......................................................................................................................... 16 
5.2.2 Peri-Operative and Post-Operative Treatment Common to Both Groups ................... 16 
5.2.3 Pre-Operative Care....................................................................................................... 17 
5.2.4 Post-Operative Care ..................................................................................................... 17 
5.2.5 Other Care .................................................................................................................... 17 
6. STUDY PROCEDURES .......................................................................................................... 17 
6.1 Patient Screening ................................................................................................................ 17 
6.2 Randomization .................................................................................................................... 18 
6.3 Frequency and Duration of Follow-up ................................................................................ 18 
6.4 Maximizing Patient Follow-up ........................................................................................... 18 
6.5 Crossovers and Co-interventions ........................................................................................ 18 
6.6 Differential Expertise Bias .................................................................................................. 19 

 
 
 
 
 
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6.7 Adjudication of Events ....................................................................................................... 19 
6.8 Blinding............................................................................................................................... 19 
7. STATISTICAL PLAN .............................................................................................................. 19 
7.1 Sample Size Determination ................................................................................................. 20 
7.2 Statistical Methods .............................................................................................................. 21 
7.2.1 Primary Analyses ......................................................................................................... 21 
7.2.2 Secondary Analyses ..................................................................................................... 21 
7.2.3 Planned Subgroup Analyses ........................................................................................ 22 
7.2.4 Frequency of Analysis ................................................................................................. 22 
7.2.5 Economic Analysis ...................................................................................................... 22 
8. DATA HANDLING AND RECORD KEEPING .................................................................... 22 
8.1 Confidentiality .................................................................................................................... 22 
8.2 Case Report Forms .............................................................................................................. 22 
8.3 Data Management ............................................................................................................... 23 
8.4 Data Monitoring Committee ............................................................................................... 23 
9. SAFETY AND ADVERSE EVENTS ...................................................................................... 24 
9.1 Definitions........................................................................................................................... 24 
9.2 Reporting of Serious Adverse Events and Unanticipated Problems Resulting in Risk to 
Subjects or Others ..................................................................................................................... 24 
9.2.1 Investigator Reporting: Notifying the Methods Center ............................................... 24 
9.2.2 Site Investigator – IRB/REB Reporting ....................................................................... 25 
10. ETHICAL CONSIDERATIONS ............................................................................................ 25 
REFERENCES ............................................................................................................................. 41 
Appendix 1: Schedule of Events Requiring Radiographs and Data Forms .................................. 44 

 
 
 
 
 
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 LIST OF TABLES 
 
Page
1. 
 
2. 
Classification of Types and Reasons for Unplanned Secondary Procedures 
 
Critical Aspects of Operative Procedure Requiring Presence of Experienced 
Surgeon 
 
26 
 
27
3. 
Sample Size Calculations Comparing Total Hip Arthroplasty (THA) and Hemi-
Arthroplasty (HA)  
 
28
4. 
Functions of the Data Monitoring Committee (DMC) 
29
 

 
 
 
 
 
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LIST OF FIGURES 
 
Page
1. 
Anatomy of the Proximal Femur and Fracture Line Level 
30
2. 
Undisplaced and Displaced Femoral Neck Fractures 
31
3. 
a. Unipolar Hemi-Arthroplasty Prosthesis 
b. Modular Unipolar Hemi-Arthroplasty Prosthesis  
c. Bipolar Hemi-Arthroplasty Prosthesis  
d. Total Hip Arthroplasty Prosthesis 
32 
33 
34 
35
4. 
Conventional Randomized Controlled Trial 
37
5. 
Expertise-Based Randomized Controlled Trial  
38
6. 
Recruitment Procedures (Baseline Radiographs & Data Collection) 
39
7. 
Post-Surgery Follow-Up Procedures 
40
8.  
Limiting Loss to Follow-Up 
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LIST OF ABBREVIATIONS 
 
Abbreviation 
Explanation 
AE 
Adverse Event 
ASA 
American Society for Anesthesiologists 
CAC 
Central Adjudication Committee 
CI 
Confidence Interval 
DAMOCLES 
Data Monitoring Committees: Lessons, Ethics, Statistics Study Group 
Charter 
D/C 
Discharge 
DMC 
Data Monitoring Committee 
DVT 
Deep Vein Thrombosis 
EQ-5D 
EuroQol-5D 
HA 
Hemi-Arthroplasty 
HEALTH 
Hip Fracture Evaluation with ALternatives of Total Hip Arthroplasty 
versus Hemi-Arthroplasty 
IHFRC 
International Hip Fracture Research Collaborative 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IU 
International Units 
LMWH 
Low Molecular Weight Heparin 
MRI 
Magnetic Resonance Imaging 
PI 
Principle Investigator 
PO 
By Mouth 
Pre-op 
Pre-operative 
Post-op 
Post-operative 
PD 
Protocol Deviation 
PTT 
Partial Thromboplaster Time 
RCT 
Randomized Controlled Trial 
REB 
Research Ethics Board 
RR 
Relative Risk 
RRR 
Relative Risk Reduction 
SF-12 
Short Form-12 
SP 
Secondary Procedure 
SPRINT 
Study to Prospectively Evaluate Reamed Intramedullary Nails in Tibial 
Fractures 
TEDS  
Thromboembolic Disease Stockings 
TUG  
Timed Up and Go 
THA 
Total Hip Arthroplasty 
W/D 
Withdraw 
WOMAC 
Western Ontario McMaster Osteoarthritis Index 
 
 

 
 
 
 
 
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STUDY SUMMARY  
 
Title 
Hip Fracture Evaluation with ALternatives of Total Hip Arthroplasty versus  
Hemi-Arthroplasty 
Short Title 
HEALTH 
Objective 
 
Our primary objective is to assess the impact of total hip arthroplasty versus 
hemi-arthroplasty (i.e., bipolar or modular unipolar) on rates of secondary 
procedures at 2 years in individuals with displaced femoral neck fractures.   
Hypothesis 
 
We hypothesize that total hip arthroplasty will have similar or lower rates of 
secondary procedures and higher functional outcome scores at 24 months 
compared with hemi-arthroplasty.   
Study 
Design 
We propose a multi-centre, concealed ‘expertise-based’ randomized trial 
design using minimization to determine patient allocation.  Surgeons across 
North America, Europe, Asia, and Australia will participate. Patients who have 
sustained a displaced femoral neck fracture will be randomized to one of two 
surgical interventions.  The first surgical intervention involves total hip 
arthroplasty (i.e., replacement of the femoral head and hip socket).  The 
second surgical intervention involves a hemi-arthroplasty (i.e., replacement of 
the femoral head only).  Each participating site will have on staff surgeons 
with expertise in both interventions to ensure adherence to the expertise-based 
design. Study personnel will monitor critical aspects of peri-operative care and 
rehabilitation. We will assess patients at hospital admission (baseline), 1 week, 
10 weeks, 6 months, 9 months, 12 months, 18 months, and 24 months after 
surgery.  Fracture eligibility when in doubt, technical placement of prostheses, 
secondary procedures, fracture-related complications, and deaths will be 
independently adjudicated.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
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1. INTRODUCTION 
 
This document is a protocol for a human research study. This is a multi-centre, blinded, 
randomized control trial to evaluate two alternative approaches (total hip arthroplasty and hemi-
arthroplasty) for treating displaced femoral neck fractures in elderly patients. Although current 
opinion among orthopaedic surgeons favours the use of arthroplasty for displaced femoral neck 
fractures, there is lack of agreement on which type of arthroplasty is optimal. The rationale for 
this study is driven by: 1) the high incidence and serious consequences of hip fractures; 2) the 
orthopaedic community’s uncertainty about the optimal type of arthroplasty; 3) a feasible and 
efficient study design; and 4) extensive support for the trial.     
 
1.1 Background   
 
Hip fractures occur in 280,000 Americans (over 5,000 per week) and 36,000 Canadians (over 
690 per week) annually (Cummings et al, 1990).  By the year 2040, the number of people aged 
65 or older will increase from 34.8 million to 77.2 million (U.S. Bureau of the Census, 1998).  
Demographic projections by Statistics Canada indicate that by the year 2041, 1 in 4 Canadians 
will be over the age of 65 years (Statistics Canada, 1994).  The number of hip fractures is likely 
to exceed 500,000 annually in the United States and 88,000 in Canada over the next 40 years 
(Johnell et al, 2004; Cooper et al, 1992; Cummings et al, 1990).  By the year 2040, the estimated 
annual health care costs will reach $9.8 billion in the United States and $650 million in Canada 
(Papadimitropolous et al, 1997).   
 
Hip fractures are associated with a 30% mortality rate at 1 year (Moran et al, 2005) and profound 
temporary, and sometimes permanent, impairment of independence and quality of life (Jongjit et 
al, 2003; Wilkins et al, 1999).  Worldwide, 4.5 million persons are disabled from hip fractures 
yearly with an expected increase to 21 million persons living with disability in the next 40 years 
(Johnell et al, 2004; Cooper et al, 1992; Cummings et al, 1990).  Hip fractures account for more 
hospital days than any other musculoskeletal injury and represent more than two thirds of all 
hospital days due to fractures (AAOS, 1999).  Length of hospital stays in Canada is estimated at 
465,000 patient-days annually with a projected increase to 1.8 million days annually by 2040 
(Papadimitropoulos et al, 1997).  The disability adjusted life-years lost as a result of hip fractures 
ranks in the top 10 of all cause disability globally (Cooper et al, 1992).  
 
Hip Fractures are anatomically classified in relation to the hip capsule as intracapsular fractures 
(i.e., femoral neck) or extracapsular fractures (i.e., inter-trochanteric and sub-trochanteric) 
(Figure 1). This trial focuses on the management of displaced fractures of the femoral neck. 
 
Femoral neck fractures may be either undisplaced (i.e., very little separation at the fracture site, 
about one third of femoral neck fractures) or displaced (i.e., greater separation, about two thirds 
of femoral neck fractures) (Figure 2).  The most popular classification system, the Garden 
Classification, identifies undisplaced fractures (i.e., Garden types I and II) and displaced 
fractures (i.e., Garden types III and IV).  Surgeons agree that internal fixation, in which a 
mechanical implant fixes the two segments of bone together, is the best way to manage 
undisplaced fractures (Bhandari et al, 2005).  For displaced fractures, the choice of internal 
fixation or arthroplasty (which involves replacing the femoral head, hemi-arthroplasty (HA), and 

 
 
 
 
 
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sometimes also the acetabulum, total hip arthroplasty (THA) (Figures 3a, 3b, 3c, and 3d) with 
prostheses) depends on patient characteristics and surgeon preference.  This trial focuses on 
displaced fractures in which patient characteristics and preference lead the attending surgeon to 
plan arthroplasty as the management approach.  
 
1.2 Hemi-Arthroplasty 
 
Advocates of hemi-arthroplasty make claims of reduced dislocation rates, lower rates of deep vein 
thrombosis (DVT), shorter operating times, less blood loss, a technically less demanding 
procedure, and lower costs than total hip arthroplasty (Poignard et al, 2011).  Newer implant 
designs (i.e., bipolar and modular unipolar hemi-arthroplasties) have reduced acetabular erosion 
(i.e., thinning out of the acetabulum) and the resultant need for a secondary procedure, a problem 
in earlier unipolar designs (i.e., single femoral head and shaft).  Furthermore, recent evidence has 
refuted a prior claim of advantages of bipolar over unipolar hemi-arthroplasties (Raia et al, 2003; 
Ong et al, 2002; Davison et al, 2001; Cornell et al, 1998).  These studies have shown no 
differences in blood loss, length of hospital stay, dislocation rates, post-operative pain, recovery of 
ambulatory status, and activities of daily living or post-operative functional outcome scores. These 
studies have established that unipolar and bipolar hemi-arthroplasties yield similar outcomes.  
 
1.3 Total Hip Arthroplasty 
 
Surgeons supporting total hip arthroplasty perceive benefits in improving patient function and 
improving quality of life (Skinner et al, 1989).  Advocates claim that modern implants have 
reduced increased dislocation rates that used to plague total hip arthroplasty, and that 
arthroplasty rates now approximate hemi-arthroplasty rates.  
 
1.4 Surgical Management of Hip Fractures – Uncertainty and Controversy 
 
The lack of definitive evidence regarding the optimal approach for surgical management has 
fueled debates at international orthopaedic surgical meetings.  A survey of 298 surgeons who 
were members of the Orthopaedic Trauma Association and European clinics affiliated with AO 
International (Davos, Switzerland) found that although surgeons agreed that arthroplasty is the 
preferred option in displaced femoral neck fractures (i.e., Garden IV) in patients aged greater 
than 60 years, they disagreed upon the optimal form of arthroplasty.  In the 60 to 80 year old 
patient, unipolar arthroplasty, bipolar arthroplasty, and total hip arthroplasty received 32%, 41%, 
and 17% endorsement, respectively.   
 
1.5 Alternative Operative Management Strategies in Femoral Neck Fractures – Direct 
Comparisons for Randomized Trials 
 
A comprehensive literature search to identify all studies relevant to the relative merits of hemi-
arthroplasty versus total hip arthroplasty for displaced femoral neck fractures identified 4 
randomized controlled trials (RCTs) comparing internal fixation, hemi-arthroplasty, and total hip 
arthroplasty.  Of these, 1 trial was an updated publication of an earlier study, and another 
reported only aggregate results for all arthroplasty.  Thus, 2 randomized trials (Ravikumar et al, 
2002; Keating et al, 2005) provided sufficient detail for statistical pooling of results.  Current 

 
 
 
 
 
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best estimates of treatment effect suggest that total hip arthroplasty reduces hip pain (RRR=0.24, 
95% CI: 2%-41%), and may reduce functional limitations (RRR=0.10, 95% CI: 24%-26%), 
when compared with hemi-arthroplasty.  The reduction in pain and improvement in function may 
come at the cost of an increased risk of hip dislocation (RR=2.95%, 95% CI: 0.40-21.74). 
Despite the trend toward an increase in hip dislocation, the data (point estimate) show a trend 
toward decrease in secondary procedure rates with hemi-arthroplasty, although the sparse data is 
associated with very wide confidence intervals (RRR=0.14, 95% CI: 53%-59%).  In addition to 
the small sample sizes, these trials are limited by lack of concealed randomization in 1 trial 
(Ravikumar et al, 2002), and a differential expertise bias (Devereaux et al, 2005), as more 
experienced surgeons usually conducted the total joint arthroplasty than the hemi-arthroplasty 
(Keating et al, 2005).         
 
1.6 Hemi-Arthroplasty versus Total Hip Arthroplasty – Indirect Comparisons from Meta-
Analyses 
 
Two meta-analyses (Lu-Yao et al, 1994; Bhandari et al, 2003) were identified that provided 
indirect comparisons of total hip arthroplasty and hemi-arthroplasty.  Lu-Yao pooled 
observational studies and randomized trials of total hip arthroplasty (N=746 patients) versus 
hemi-arthroplasty (N=4,530 patients), and found reductions in the risk of secondary procedures, 
mortality, wound infection, and hip pain with total hip arthroplasty. Bhandari’s meta-analysis 
restricted to randomized trials (N=662 patients) suggested similar rates of secondary procedures, 
decreased mortality, decreased infection rates, and large benefits in patient function with total 
hip arthroplasty.  Both meta-analyses reported at least 2-fold higher hip dislocation rates with 
total hip arthroplasty.  
 
In summary, both direct and indirect evidence suggests substantial benefit of total hip 
arthroplasty over hemi-arthroplasty in decreased pain and improved function.  Both direct and 
indirect evidence suggest increased rates of dislocation with total hip arthroplasty.  Despite this 
increased dislocation rate, indirect evidence suggests similar secondary procedure and mortality 
rates with the 2 procedures.  While direct evidence is consistent with similar rates of secondary 
procedures and mortality, the data from direct comparisons are so sparse as to be uninformative. 
 
 
2. STUDY OBJECTIVES 
 
2.1 Primary Objective   
 
The primary objective is to assess the impact of total hip arthroplasty versus hemi-arthroplasty 
(i.e., bipolar or modular unipolar) on rates of secondary procedures at 2 years in individuals with 
displaced femoral neck fractures.   
 
2.2 Secondary Objectives 
 
Secondary objectives are: 
   

 
 
 
 
 
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1. To examine the effect of total hip arthroplasty versus hemi-arthroplasty on health-related 
quality of life (Short Form-12, SF-12), functional outcomes and mobility (Western 
Ontario McMaster Osteoarthritis Index, WOMAC, and Timed Up and Go Test, TUG), 
and health outcome measures (EuroQol-5 Dimensions, EQ-5D).   
2. To evaluate the effect of total hip arthroplasty versus hemi-arthroplasty on mortality. 
3. To evaluate the effect of total hip arthroplasty versus hemi-arthroplasty on hip-related 
complications including: 
• Peri-prosthetic fracture 
• Hip instability or dislocation 
• Implant failure (loosening/subsidence and breakage) 
• Wound healing problems (including superficial/deep infection, wound necrosis) 
• Soft tissue problems (i.e. pseudotumor) 
• Heterotopic ossification 
• Abductor failure 
• Implant wear and corrosion 
• Osteolysis 
• Neurovascular injury 
• Decreased function 
• Pain  
 
3. STUDY DESIGN 
 
3.1 Study Overview 
 
HEALTH is a multi-centre, concealed ‘expertise-based’ randomized trial of 1,434 patients who 
have sustained a displaced femoral neck fracture. Minimization will be used to determine patient 
allocation.  Surgeons across North America, Europe, Australia, and Asia will participate.  In 
conventional surgical hip fracture trials, all surgeons involved in the trial have performed both 
total hip arthroplasties and hemi-arthroplasties based on the randomization process (Figure 4). 
HEALTH will utilize an alternative randomized trial design that allocates patients to surgeons 
with expertise in total hip arthroplasty or hemi arthroplasty (Figure 5). Based upon their 
expertise, surgeons will use one of two surgical strategies in patients who have sustained a 
displaced femoral neck fracture.  The first strategy involves total hip arthroplasty (i.e., 
replacement of the femoral head and hip socket).  The second treatment strategy involves a 
hemi-arthroplasty (i.e., replacement of the femoral head only).   
 
Study personnel will monitor critical aspects of peri-operative care and rehabilitation. Patients 
will be assessed at hospital admission (baseline), 1 week, 10 weeks, 6 months, 9 months, 12 
months, 18 months, and 24 months after surgery. Fracture eligibility, technical placement of 
prostheses, secondary procedures, hip-related complications, and deaths will be independently 
adjudicated.  
 
3.1.1 Expertise-Based Randomized Controlled Trial   
HEALTH will utilize an alternative randomized trial design that allocates patients to surgeons 
with expertise in total hip arthroplasty who are committed to performing total hip arthroplasty, or 
to surgeons with expertise in hemi-arthroplasty who are committed to performing hemi-

 
 
 
 
 
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arthroplasty (Figure 5).  Those surgeons who feel confident enough in both will perform both 
total hip arthroplasty and hemi-arthroplasty.  Devereaux and colleagues have outlined the 
advantages of this trial design, which include the following:  
1. Elimination of differential expertise bias in which, in conventional designs, a larger 
proportion of surgeons are expert in one procedure under investigation than the other. 
2. Differential performance, co-intervention, data collection, and outcome assessment are 
less likely than in conventional RCT. 
3. Procedural crossovers are less likely because surgeons are committed and experienced in 
their procedures. 
4. Ethical concerns are reduced because all surgeries are conducted by surgeons with 
expertise and conviction concerning the procedure (Devereaux et al, 2005).  
 
 
3.2 Proposed Primary and Secondary Outcome Measures 
 
3.2.1 Primary Outcomes  
The primary outcome is any unplanned secondary procedure within 2 years of the initial joint 
replacement surgery.  A Central Adjudication Committee will review each reported secondary 
procedure to determine that they are study events (i.e. unplanned) and they will confirm the type 
of the procedure and the reason for the procedure (Table 1).  
 
 Specific unplanned secondary procedures include:  
1. Closed reduction of hip dislocation 
2. Open reduction of hip dislocation 
3. Open reduction of fracture 
4. Soft tissue procedure 
5. Insertion of antibiotic spacer 
6. Full implant exchange  
7. Partial implant exchange – stem only 
8. Partial implant exchange - head only 
9. Partial implant exchange - liner only 
10. Partial implant exchange - head and liner 
11. Partial implant exchange – acetabular component only  
12. Partial implant exchange – acetabular component and head  
13. Implant adjustment – re-orientation of the stem 
14. Implant adjustment – re-orientation of the acetabulum component 
15. Implant removal with no replacement 
16. Excision heterotopic ossification 
17. Supplementary fixation  
 
Classification of the reason for secondary procedures is as follows:  
1. Treat a peri-prosthetic fracture 
2. Treat hip instability or dislocation 
3. Treat infection – superficial 
4. Treat infection – deep 
5. Treat wound necrosis 
6. Treat another wound healing problem 

 
 
 
 
 
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7. Remove heterotopic ossification 
8. Manage abductor failure 
9. Manage another soft tissue problem (i.e. pseudotumor)  
10. Correct implant failure –loosening or subsidence 
11. Correct implant failure - breakage 
12. Treat implant wear  
13. Treat osteolysis 
14. Treat implant corrosion 
15. Improve function 
16. Relieve pain 
 
 
 
        
3.2.2 Secondary Outcomes 
Secondary outcomes will include:  
 
Functional outcome and quality of life will be measured using self-administered and interview-
administered questionnaires.  Functional outcome questionnaires will include a generic health 
status measurement instrument (SF-12), a hip function and pain questionnaire (WOMAC), a 
health outcome measure (EQ-5D), and a functional mobility test (TUG). HEALTH will further 
report the effect of total hip arthroplasty versus hemi-arthroplasty on mortality and hip-related 
complications including: 
• Peri-prosthetic fracture 
• Hip instability or dislocation 
• Implant failure (loosening/subsidence and breakage) 
• Wound healing problems (including superficial/deep infection, wound necrosis) 
• Soft tissue problems (i.e. pseudotumor) 
• Heterotopic ossification 
• Abductor failure 
• Implant wear and corrosion 
• Osteolysis 
• Neurovascular injury 
• Decreased function 
• Pain  
 
At 1 week, 10 weeks, 6 months, 12 months, and 24 months after surgery the research coordinator 
or nurse will ascertain patient status via clinic visits and completion of self-administered quality 
of life forms (SF-12, WOMAC, and EQ-5D) and the functional mobility test (TUG) (Figure 7).  
During all visits the research coordinator or nurse should be prepared to conduct interview-
administered data collection if patients are unable to complete the self-administered forms. Hip-
related complications will also be documented at each follow-up.  Other serious adverse events 
and non-hip related complications will also be recorded (refer to section 9.0).  At 9 months and 
18 months after surgery the research coordinator or nurse will ascertain patient status (i.e., 
secondary procedures, hip-related complications, deaths), as well as administer quality of life 
questionnaires (SF-12, WOMAC, and EQ-5D) via telephone calls and verifying information in 
medical records.   
      

 
 
 
 
 
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The SF-12 questionnaire was developed from the Medical Outcomes Study (McHorney et al, 
1992).  It is a self-administered, 12-item questionnaire that measures health-related quality of life 
in 8 domains. Both physical and mental summary scores can be obtained. Each domain is scored 
separately from 0 (lowest level) to 100 (highest level) (Ware et al, 1996).  
 
The WOMAC index is self-administered and assesses the three dimensions of pain, disability 
and joint stiffness in knee and hip osteoarthritis using a battery of 24 questions (Bellamy et al, 
1988).   
 
The EQ-5D is a comprehensive, compact health status classification and health state preference 
system (Brooks et al, 2003). Patients who are completing the self-administered version of the 
EQ-5D will also be asked to complete a test version of the EQ-5D questions that uses 5-level 
response options.  This data will be used in a sub-study comparing the test version to the 
validated version, which uses 3-level response options.   
 
 
The TUG is a simple test that involves documenting the time,  in  seconds, taken for subjects to 
“rise from a standard arm chair, walk to a line on the floor 3 meters away, turn, return, and sit 
down again” (Podsiadlo and Richardson, 1991).  
 
 
4. SUBJECT SELECTION AND RISK 
 
4.1 Inclusion and Exclusion Criteria 
 
4.1.1 Inclusion Criteria 
1. Adult men or women aged 50 years and older (with no upper age limit). 
2. Fracture of the femoral neck confirmed with either anteroposterior or lateral hip radiographs, 
computed tomography, or magnetic resonance imaging (MRI).  
3. Displaced fracture that is not, in the judgment of the attending surgeon, optimally managed by 
reduction and internal fixation. 
4. Operative treatment within 3 days (i.e. 72 hours) of the patient being medically cleared for 
surgery.  
5. Patient was ambulatory prior to fracture, though they may have used an aid such as a cane or a 
walker.  
6. Anticipated medical optimization for arthroplasty of the hip. 
7. Provision of informed consent by patient or proxy.  
8. Low energy fracture (defined as a fall from standing height). 
9. No other major trauma (defined as an Injury Severity Score <17*).  
10. Assurance that surgeons with expertise in both total hip arthroplasty and hemi-arthroplasty 
are available to perform surgery. Note: Surgeons do not need to be experts in both techniques. 
*The Injury Severity Score (ISS) is an anatomical scoring system that provides an overall score 
for patients with multiple injuries. Each injury is assigned an Abbreviated Injury Scale (AIS) 
score and is allocated to one of six body regions (Head, Face, Chest, Abdomen, Extremities 
(including Pelvis), and External). Only the highest AIS score in each body region is used. The 3 
most severely injured body regions have their score squared and added together to produce the 
ISS score. More information can be found at: http://www.trauma.org/archive/scores/iss.html.  

 
 
 
 
 
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4.1.2 Exclusion Criteria  
1. Patient not suitable for hemi-arthroplasty (e.g. inflammatory arthritis, rheumatoid 
arthritis, pathologic fracture (secondary to cancer), or severe osteoarthritis of the hip).   
2. Associated major injuries of the lower extremity (i.e., ipsilateral or contralateral fractures 
of the foot, ankle, tibia, fibula, knee, or femur; dislocations of the ankle, knee, or hip; or 
femoral head defects or fracture). 
3. Retained hardware around the affected hip that will interfere with arthroplasty.  
4. Infection around the hip (soft tissue or bone).  
5. Patients with a disorder of bone metabolism other than osteoporosis (i.e., Paget’s disease, 
renal osteodystrophy, osteomalacia). 
6. Patients with a previous history of frank dementia that would interfere with assessment of 
the primary outcome (i.e., secondary procedures at 2 years).  
7. Likely problems, in the judgment of the investigators, with maintaining follow-up (i.e., 
patients with no fixed address, report a plan to move out of town, or intellectually 
challenged patients without adequate family support).  
8. Patients whose fracture occurred as a result of an act of violence. 
For Item 6 above, patients with a history of frank dementia are unlikely to survive to 2 years, 
which will cause problems with assessment of the primary outcome. 
Exclusion of a patient because of enrolment in another ongoing drug or surgical intervention trial 
will be left to the discretion of the attending surgeon, on a case-by-case basis.   
  
 
 
 
5. STUDY INTERVENTIONS 
 
5.1 Arthroplasty Procedures 
 
5.1.1 Total Hip Arthroplasty 
To optimize feasibility and applicability of results, this study will not standardize the surgical 
approach, the use of cemented components, the implant manufacturer, or femoral head size.  
Surgeons will use the manufacturer specific implant guides and jigs for insertion of the total joint 
arthroplasty. Proscribed approaches will include minimally invasive total hip arthroplasty (i.e., 2 
incision approaches) and hinged prostheses or capture cups. 
 
5.1.2 Hemi-Arthroplasty 
Surgeons will use modern implants for hemi-arthroplasty excluding non-modular, non-canal 
filling unipolar implants such as Moore’s and Thompson’s prostheses.  The choice of modular 
unipolar versus bipolar hemi-arthroplasty will not be standardized. This study will not 
standardize whether implants are inserted with cement or with a press-fit design.  Surgeons will 
use the manufacturer specific implant guides and jigs for insertion of the total joint arthroplasty. 
The manufacturer, implant material, and bearing surface of the implant will be documented in all 
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5.2 Standardization of Procedures and Peri-Operative Care 
Given the inherent variability in practice patterns among orthopaedic surgeons, it is important to 
ensure that surgeons adhere as closely as possible to the surgical management protocol and to 
current accepted practice. 
 
To ensure that all participating surgeons perform their respective procedures in a similar manner, 
they will be required to review training materials that highlight critical aspects of the surgical 
protocols which are posted on the HEALTH trial website (clarityrand.mcmaster.ca/HEALTH).  
 
Several strategies will be instituted to ensure adherence to the protocol, including the following:  
1. Interactive educational sessions or presentations with orthopaedic trainees, nurses, and 
fellows at the beginning of their rotations. 
2. Daily reminders (i.e., email and verbal, as well as posters and pocket cards) for on call 
surgeons by the site research coordinator.    
3. Weekly quality control report forms to flag protocol violations. 
4. Monthly newsletters re-emphasizing important aspects of the protocol and highlighting 
compliance figures across all participating sites. 
5. Personal telephone calls from the principal investigator or project coordinator to site 
investigators when protocol violations occur.   
6. 24-hour mobile phone contacts for any queries regarding the study protocol. 
7. Frequent investigator’s meetings to discuss protocol violations and strategies to improve 
adherence.   
8. An active trial website with information updates.   
 
5.2.1 Threshold Performance for Expertise in Total Hip Arthroplasty and Hemi-Arthroplasty 
Surgeons participating in the HEALTH trial are required to meet both of the following 2 criteria 
for expertise for either total hip arthroplasty or hemi-arthroplasty:  
1. Surgeons must have performed at least 50 procedures (either THA or HA) in their career 
(including residency experience in which they assumed responsibility for the procedure).  
2. Surgeons must continue to perform at least 5 procedures (either THA or HA) in the year 
prior to trial start date, as well as each year for the duration of the study.   
 
Surgeons who meet the threshold for both total hip arthroplasty and hemi-arthroplasty will 
perform both procedures if no overwhelming bias in favour of one procedure is evident. A 
surgeon will be considered biased for an approach if he/she has performed less than 5 cases of 
either procedure in his/her last 50 procedures for a displaced femoral neck fracture.  
 
Residents and fellows may perform the procedures under the supervision of a participating 
attending surgeon.  The surgeon most responsible for the case must meet threshold expertise 
criteria and must be present in the operating room for the critical aspects of the procedure (Table 
2).  
 
5.2.2 Peri-Operative and Post-Operative Treatment Common to Both Groups 
To ensure similar peri-operative regimens, it is recommended that participating centres 
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5.2.3 Pre-Operative Care  
1. Pre-operative antibiotic prophylaxis (i.e., cephalosporin, Ancef, or equivalent coverage). 
2. Thromboprophylaxis (i.e., Thromboembolic Disease Stockings (TEDS), pneumatic 
compression boots, or medical prophylaxis to be discontinued in sufficient time to allow 
surgery as guided by International Normalized Ratio (INR) / Partial Thromboplasty Time 
(PTT)).   
3. Medical consultation to optimize condition prior to surgery.   
 
5.2.4 Post-Operative Care 
1. Antibiotic prophylaxis (i.e., cephalosporin or equivalent) for 24 hours.  
2. Thromboprophylaxis with unfractionated heparin, Low Molecular Weight Heparin 
(LMWH), warfarin, anti-platelet agents, or intermittent pneumatic compression boots.  
3. Weightbearing as tolerated will be allowed as patients autoprotect the affected hip during 
rehabilitation.  Post-surgery, patients will be weightbearing as tolerated, and then 
advanced according to the attending surgeon’s best judgment (i.e., touch weightbearing 
will be permitted, and then advanced according to the surgeon’s best judgment).   
4. Calcium 600 mg by mouth (PO) daily and vitamin D 1000 International Units (IU) per 
day (provided there are no contraindications) and further investigation and treatment of 
osteoporosis as recommended by a local osteoporosis expert/consultant. 
5. Appropriate nutritional assessment with administration of oral micronutrient feeds as 
needed. 
 
5.2.5 Other Care  
Due to a lack of evidence favouring a particular approach, the following will be recorded but not 
standardized: 
1. Use of pre-operative traction.   
2. Surgical delay. 
3. Type of anesthetic (i.e., general or regional).   
4. Physiotherapy and rehabilitation programs.    
 
6. STUDY PROCEDURES 
 
6.1 Patient Screening 
 
All patients presenting to participating surgeons with a diagnosed displaced femoral neck 
fracture amenable to arthroplasty will be screened.  Such patients will be classified as: 
1. Excluded (if they subsequently do not meet the eligibility criteria).  
2. Missed (due to error or staff availability).  
3. Eligible and randomized (if applicable).   
If the participating surgeon identifies the eligible patient who consents to randomization, the 
surgeon or delegate will contact the automated computer randomization system by Internet (see 
Section 6.2) (Figure 6).  The surgeon or delegate will enter in the patient’s prognostic factors 
(Section 6.2).  The automated system will then allocate the patient into 1 of 2 groups (total hip 
arthroplasty or hemi arthroplasty).  
 

 
 
 
 
 
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6.2 Randomization 
 
Allocation will be concealed using a centralized 24-hour computerized randomization system 
that will allow Internet-based randomization.  Patients will be the unit of randomization.  To 
protect against prognostic imbalance between groups, minimization will be used to ensure 
balance between intervention groups for several patient factors.  The minimization approach 
measures marginally each prognostic variable and sums over the variables.   
 
Unlike random permuted block within strata, minimization works toward minimizing the total 
imbalance for all factors together instead of considering mutually exclusive subgroups (Pocock, 
2005).  Based upon our international survey of surgeons (Bhandari et al, 2005), and current 
evidence (Gillespie, 2001), we will minimize for the following prognostic factors:  
1. Age (i.e., 50-80 years or >80 years). 
2. Pre-fracture living setting (i.e., institutionalized or not institutionalized). 
3. Pre-fracture functional status (i.e., using aid or independent ambulator). 
4. American Society for Anesthesiologists (ASA) Class (i.e., Class I/II or III/IV/V). 
5. Centre number. 
 
6.3 Frequency and Duration of Follow-up 
 
All patients will be followed for a period of 2 years (Figures 6 and 7).  In addition, at the 2-year 
follow-up visit, the surgeon will document any secondary procedures that may be planned for the 
patient. Clinical assessments will occur at the time of admission to hospital (baseline), 1 week 
(24 hours – 10 days window), 10 weeks (8-12 weeks window), 6 months (5-7 months window), 
12 months (11-13 months window), and 24 months (≥24 months window) after surgery. X-rays 
will be taken at the time of admission to hospital (baseline), within 48 hours post surgery, and at 
10 weeks (8-12 weeks window), 12 months (11-13 months window), and 24 months (≥24 
months window) post surgery.  At 9 months (8-10 months window) and 18 months (17-19 
months window) after surgery the research coordinator or nurse will ascertain patient status (i.e., 
secondary procedures, hip-related complications, deaths, as well as interview-administered 
quality of life questionnaires (SF-12, WOMAC, and EQ-5D)) via telephone calls and verifying 
information within medical records.  At 1 week (24 hours – 10 days window), 10 weeks (8-12 
weeks window), 6 months (5-7 months window), 12 months (11-13 months window), and 24 
months (≥24 months window) post surgery the research coordinator or nurse will ascertain 
patient status via clinical visits and completion of self-administered quality of life questionnaires 
(SF-12, WOMAC, and EQ-5D), and the functional mobility test (TUG).   
 
6.4 Maximizing Patient Follow-up 
 
Previous trials in hip fracture surgery have lost up to 50% of patients to follow-up (Bhandari et 
al, 2003).  To avoid this problem, the strategies outlined in Figure 8 will be used to minimize 
loss to follow-up.   
 
6.5 Crossovers and Co-interventions 
 

 
 
 
 
 
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Crossovers are extremely unlikely between total hip arthroplasty and hemi-arthroplasty as 
patients will be treated by surgeons with expertise to the allocated procedure.  Any patients who 
do cross over will be analyzed in the group to which they were allocated, maintaining the 
intention to treat approach of the analysis.  Surgical co-intervention such as a general, 
neurosurgical, or orthopaedic procedure may confound outcomes. The standardization of 
management protocols and the expertise-based trial design will limit co-intervention, and the use 
of drugs that affect the bone, and major additional procedures that patients undergo will both be 
recorded. Research coordinators will record all medications such as a bisphosphonates, vitamin 
D, calcium, hormone replacement therapy, selective estrogen receptor modulators, calcitonin, 
and anabolic steroid therapy used concurrently in included patients.   
 
6.6 Differential Expertise Bias 
 
The HEALTH trial design will eliminate differential expertise bias by establishing a minimal 
threshold for expertise, as well as ensuring that all surgeons performing either hemi-arthroplasty 
or total hip arthroplasty are dedicated to and expert in the procedure.  
 
6.7 Adjudication of Events 
 
An independent Central Adjudication Committee (CAC) will review cases where fracture 
eligibility is in doubt and the technical placement of prostheses. They will also review secondary 
procedures and hip-related complications, and will decide if a secondary procedure and/or hip-
related complication meeting study criteria has occurred. Planned secondary procedures will not 
be considered study events. The CAC will also review cases of mortality. Adjudication will 
occur after patients have completed their 2 year follow-up. Any disagreements among the CAC 
members will be resolved during monthly conference calls. The CAC will include 3 orthopaedic 
surgeons who specialize in orthopaedic trauma and have expertise in research methodology and 
experience with clinical trials. 
 
All centres will submit digital x-rays to the Methods Centre, and fax all relevant hospital records.  
All relevant patient records devoid of personal identifiers (i.e., DataFax forms, chart notes, and 
x-rays) will be posted on a specially designed, and password protected, Internet website for study 
adjudication. Additional information will be requested from the participating site to clarify areas 
of uncertainty. All decisions made by the committee will be final. 
 
6.8 Blinding 
 
While surgeons, patients, and outcome assessors cannot be blinded to the surgical arms (i.e., 
total hip arthroplasty or hemi-arthroplasty), data analysts will remain blinded throughout the 
trial.  The primary outcome (secondary procedures) is objective and lack of blinding introduces 
minimal threats to validity. 
 
 
7. STATISTICAL PLAN 
 

 
 
 
 
 
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7.1 Sample Size Determination 
 
The choice of sample size is based upon a comparison for the primary outcome (secondary 
procedures) of THA versus HA. All statistical hypotheses will be two-sided. Alpha levels of 0.05 
for the primary and 0.01 for the secondary outcomes were chosen. Previous studies have 
reported secondary procedure rates in hip fracture patients treated with HA that have ranged 
from 4 to 10% at one year, with a weighted pooled risk of 5.3% (95% CI 3.2 to 8.9%) in a fixed 
effect meta-analysis, or 4.9% (95% CI 2.6 to 9.2%) using random effects. A pooled estimate 
from 5 randomized trials comparing THA with HA gave a relative risk of 1.67 (95% CI 0.86 to 
3.24, p=0.13) (Table 3a). 
 
The sample size calculation reflects the proposed approach to the primary analysis, which will 
use the Cox proportional hazards model. The calculation is based on methods described by 
Collett (Collett, 1994). The goal is to calculate the required number of patients that will yield a 
sufficient number of outcome events (secondary procedures) in order to have adequate statistical 
power for a given size of treatment effect. This was done taking into account the anticipated 
secondary procedure rates in the HA group, postulated values of the relative risk increase 
associated with THA vs. HA, and the rates of mortality and loss to follow-up. Because some of 
these inputs are expected to change over the two year period of follow-up, the expected number 
of person-years of follow-up and the expected numbers of study events in each group were 
calculated, initially for the first year of follow-up; the calculation was then repeated for the 
second year of follow-up, after having estimated the number of patients in each group who 
would survive, be event-free, and available for continued follow-up between 12 and 24 months 
post-randomization.  
 
Based upon aggregate data from the pilot study, annual mortality rates of 15% and a loss to 
follow-up of 5% in each group were assumed, these rates applying to each of the two years of 
follow-up. Informed by the meta-analysis, the following assumptions were made: a one year risk 
of having a secondary procedure of 5% in the HA group and a risk of 1% in the second year. 
Various values of the relative risk reduction (HA vs. THA) were then used to identify the 
specific value that would correspond to a cumulative risk difference between THA and HA of 
5% after 2 years. This figure was identified in a survey of participating surgeons as the 
minimally important difference to clinicians. Annual event risks by group were converted into 
equivalent hazard rates, assuming for simplicity that the hazard rate would be approximately 
constant within each of the two years. It is estimated that approximately 72% of the group 
receiving THA and 76% of the group receiving HA will be event-free and available for further 
follow-up at the start of the second year. The sample size was increased to allow for a combined 
7.6% crossover rate from the assigned to the alternate treatment, based on pilot data. These 
assumptions lead to a required total sample size of 1,316 patients, which will yield an expected 
number of 96 secondary procedures. The associated relative risk reduction (RRR) is 0.45.  
These calculations were repeated after replacing the 5% event risk at one year for HA by 4% and 
6% and leaving the other factors unchanged (Table 3b). To account for potential surgeon level 
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For the secondary outcomes, an important difference in SF-12 is considered to correspond to a 
moderate effect as reported by Cohen (Cohen, 1988) as well as a minimally important difference 
in the SF-12 as reported by Ware (Ware & Sherbourne, 1992).  In both cases, the value is at least 
half the standard deviation, equivalent to 4-point difference in score.  Specifying an alpha 
level=0.05, a beta=0.20 (study power=80) and a standard deviation of 8 (Jaglal et al, 2000), a 
sample of at least 128 patients (64 per group) is required to ensure detection of a half standard 
deviation improvement.  In clinical drug trials, a 9-point change in WOMAC functional score 
was accepted as a minimally significant improvement in symptoms (Turbach et al, 2005). In this 
study, at least 90 patients (45 per group) would be required to detect this difference (alpha 
level=0.05, beta=0.20, σ =15).  Previous studies have found a standard deviation of 0.20 for the 
EQ-5D (Tidermark et al, 2003). To detect a difference of 0.10 (half the standard deviation) with 
80% power at an alpha level of 0.05, this study requires a total of 128 patients (64 per group).  
Thus, in all circumstances, the desired sample size of 1,434 patients will be sufficient to detect 
clinically meaningful differences in the secondary measures of outcome.   
 
7.2 Statistical Methods 
 
7.2.1 Primary Analyses 
All outcome analyses will be performed by an intention to treat approach.  To evaluate the effect 
of total hip arthroplasty versus hemi-arthroplasty on time to secondary procedures (the primary 
outcome), a Cox proportional hazards model will be used with the following covariates:   
1. Age (i.e., 50-80 years or >80 years). 
2. Pre-fracture living setting (i.e., institutionalized or not institutionalized). 
3. Pre-fracture functional status (i.e., using aid or independent ambulator). 
4. American Society for Anesthesiologists (ASA) Class (i.e., Class I/II or III/IV/V). 
5. Centre number. 
 
Results will be reported as hazard ratios with 95% confidence intervals.  Kaplan-Meier curves 
will be constructed. 
 
 
 
7.2.2 Secondary Analyses  
A generalized linear model will estimate the effect of total hip arthroplasty versus hemi-
arthroplasty on quality of life (SF-12), function (WOMAC), health outcome (EQ-5D), and 
mobility (TUG) at follow-up using the following covariates that are included in our 
minimization procedure:  
1. Age (i.e., 50-80 years or >80 years). 
2. Pre-fracture living setting (i.e., institutionalized or not institutionalized). 
3. Pre-fracture functional status (i.e., using aid or independent ambulator). 
4. American Society of Anesthesiologists (ASA) Class (i.e., Class I/II or III/IV/V). 
5. Centre number.   
 
Cox proportional hazards modeling will estimate the relative effect of total hip arthroplasty 
versus hemi-arthroplasty on time to mortality and hip-related complications.  Results will be 
reported as hazard ratios with 95% confidence intervals.  Kaplan-Meier curves will be 
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7.2.3 Planned Subgroup Analyses 
There are no planned subgroup analyses. 
 
7.2.4 Frequency of Analysis 
The approach to interim analyses is guided by a desire to avoid spuriously inflated estimates of 
treatment effect (Montori et al, 2005; Briel et al, 2009). A single interim analysis will be 
performed when 60% of the planned patient-years of follow-up have been accrued.  The data 
analyst will present the results of these analyses to our independent Data Monitoring Committee 
(see Section 8.4). The committee will be guided by the O’Brien-Fleming stopping rule based on 
the primary outcome, which will maintain the overall specified type I error rate at 5% for the 
combined interim and final analyses. According to this rule, the required p-value to declare a 
significant result at the interim analysis is 0.00762, and at the final analysis, the required p-value 
is 0.0476. The rule is conservative, making it difficult to stop the trial early unless a large 
treatment effect is observed. We will only apply our stopping rule to the primary outcome.  The 
secondary functional outcomes may demonstrate significance quickly due to the nature of the 
instruments, but we will not stop the study for that reason. No one other than committee 
members will be aware of the data on which the committee makes its decision, and no one 
involved in the study will be aware of the content of their deliberations. 
 
7.2.5 Economic Analysis 
Including an economic analysis in the current proposal will substantially increase the resource 
requirements. To ensure the future feasibility of an economic analysis, patient utilities will be 
collected utilizing the EQ-5D and a separate proposal for additional funds will be developed to 
conduct a full economic analysis. 
 
 
8. DATA HANDLING AND RECORD KEEPING 
 
8.1 Confidentiality 
 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). 
Those regulations require a signed subject authorization informing the subject of the following:  
1. what protected health information (PHI) will be collected from subjects in this study,  
2. who will have access to that information and why,  
3. who will use or disclose that information, and  
4. the rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization. For subjects that have revoked authorization to collect or use PHI, attempts should 
be made to obtain permission to collect at least vital status (i.e. that the subject is alive) at the 
end of their scheduled study period. 
 
8.2 Case Report Forms 
 

 
 
 
 
 
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The CRFs are the primary data collection instrument for the study. All data requested on the 
CRF must be recorded. All missing data must be explained. If a space on the CRF is left blank 
because the procedure was not done or the question was not asked, write “N/D”. If the item is not 
applicable to the individual case, write “N/A”. All entries should be printed legibly in black ink. 
If any entry error has been made, to correct such an error, draw a single straight line through the 
incorrect entry and enter the correct data above it. All such changes must be initialed and dated.  
 
8.3 Data Management 
 
Data from the case report forms will be entered into the study’s electronic data capture system 
(iDataFax). Upon receipt of the data, the staff at the Methods Centre will make a visual check of 
each form. Methods Centre personnel will query all missing data, implausible data, and 
inconsistencies. Frequent reports summarizing all queries will be sent to the research 
coordinators from each clinical centre by email. The quality control report will include the 
following: 
1. Patients entered into the trial. 
2. Completed follow-up visits. 
3. Outstanding data clarification requests. 
4. Date when patient’s next follow-up visit is due. 
5. Overdue assessments. 
 
Follow-up telephone calls will be made frequently to ensure problems are corrected. Once 
problems have been resolved and the case report forms are deemed complete and accurate, the 
data are marked clean in the iDataFax system. The system has built-in range and logic checks.  
When logic errors have been corrected, the information is entered into the master file containing 
data suitable for analysis.   
 
8.4 Data Monitoring Committee 
 
The Data Monitoring Committee (DMC) will be comprised of at least 4 members who remain 
completely independent of the study investigators and have never received any honoraria from, 
or held stock in any of the manufacturers whose products are used in this trial.  The DMC 
members will span the spectrum from clinical experts with prior trial experience, a clinical trial 
methodologist, and a biostatistician.  The DMC function in an advisory rather than executive 
capacity and its duties are detailed in Table 4.   
 
When the DMC decide that a definitive answer to the trial question has been achieved (in terms 
of efficacy, safety, or futility) they will unblind the Principal Investigator.  These terms of 
reference and functions are derived from the principles established by the Data Monitoring 
Committees: Lessons, Ethics, Statistics (DAMOCLES) Study Group charter.  They have been 
approved by the ethics committees and implemented successfully in several international multi-
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9. SAFETY AND ADVERSE EVENTS 
 
9.1 Definitions 
 
Adverse Event (AE)  
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in 
severity during the course of the study.  
 
Serious Adverse Event (SAE) 
Adverse events are classified as serious or non-serious. A serious adverse event is any AE that 
is:  
1. fatal,  
2. life-threatening,  
3. requires or prolongs hospital stay,  
4. results in persistent or significant disability or incapacity,  
5. a congenital anomaly or birth defect, or  
6. an important medical event.  
 
Unanticipated Problems Resulting in Risk to Subjects or Others  
Any incident, experience, or outcome that meets all of the following criteria:  
1. unexpected in nature, severity, or frequency (i.e. not described in study-related 
documents such as the IRB-approved protocol or consent form, the investigators 
brochure, etc.),  
2. related or possibly related to participation in the research (i.e. possibly related means 
there is a reasonable possibility that the incident experience, or outcome may have been 
caused by the procedures involved in the research),  
3. suggests that the research places subjects or others at greater risk of harm (including 
physical, psychological, economic, or social harm).  
 
Unanticipated problems resulting in risk to volunteers or others encompass more than what one 
usually thinks of as adverse events. “Problems involving risk” may not necessarily result in 
harm. For example, misplacing a volunteer’s study records containing identifiable private 
information introduces the risk of breach of confidentiality. Confidentiality may or may not be 
breached, but either way this would be a reportable event. Risks to others must also be reported. 
For example, an unexpected outburst during questionnaire administration by a volunteer that puts 
study staff at risk would be a reportable event.  
 
9.2 Reporting of Serious Adverse Events and Unanticipated Problems Resulting in Risk to 
Subjects or Others 
 
All serious adverse events and unanticipated problems resulting in risk to subjects or others are 
to be reported to the Methods Center immediately.  
 
9.2.1 Investigator Reporting: Notifying the Methods Center 
Any AEs and SAEs must be reported promptly to the Methods Center by completing the AE 
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keep a copy of this AE/SAE Form on file at the study site. The AE/SAE form should include a 
written narrative and any other information that will assist the understanding of the event. 
Significant new information on ongoing Serious Adverse Events should be provided promptly to 
the Methods Center by updating the AE/SAE form. Unanticipated problems resulting in risk to 
subjects or others are to be reported to the Methods Center by either fax or email. 
 
9.2.2 Site Investigator – IRB/REB Reporting 
Investigators are responsible for reporting AEs, SAEs, and unanticipated problems resulting in 
risk to subjects or others to their local IRB/REB. Investigators are responsible for complying 
with their local IRB’s/REB’s reporting requirements. Copies of each report and documentation 
of IRB/REB notification and receipt will be kept in the investigator’s study file. 
 
 
10. ETHICAL CONSIDERATIONS 
 
This protocol and any amendments will be submitted to a properly constituted independent REB 
or IRB, in agreement with local legal prescriptions, for formal approval of the study conduct. 
The decision of the REB/IRB concerning the conduct of the study will be made in writing to the 
investigator and a copy of this decision will be provided to the Methods Center before 
commencement of this study.  
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study. The consent form will be submitted with the protocol for review and approval by the 
REB/IRB for the study. The formal consent of a subject, using the REB/IRB-approved consent 
form, must be obtained before that subject undergoes any study procedure. The consent form 
must be signed by the subject or legally authorized representative, and the investigator-
designated research professional obtaining the consent. 

 
 
 
 
 
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Table 1: Classification of Types and Reasons for Unplanned Secondary Procedures 
 
Specific unplanned secondary procedures 
include:  
Classification of the reason for secondary 
procedures is as follows:  
1. Closed reduction of hip dislocation 
2. Open reduction of hip dislocation 
3. Open reduction of fracture 
4. Soft tissue procedure 
5. Insertion of antibiotic spacer 
6. Full implant exchange  
7. Partial implant exchange – stem only 
8. Partial implant exchange - head only 
9. Partial implant exchange - liner only 
10. Partial implant exchange - head and 
liner 
11. Partial implant exchange – acetabular 
component only  
12. Partial implant exchange – acetabular 
component and head  
13. Implant adjustment – re-orientation of 
the stem 
14. Implant adjustment – re-orientation of 
the acetabulum component 
15. Implant removal with no replacement 
16. Excision heterotopic ossification 
17. Supplementary fixation  
 
1. Treat a peri-prosthetic fracture 
2. Treat hip instability or dislocation 
3. Treat infection – superficial 
4. Treat infection – deep 
5. Treat wound necrosis 
6. Treat another wound healing problem 
7. Remove heterotopic ossification 
8. Manage abductor failure 
9. Manage another soft tissue problem 
(i.e. pseudotumor)  
10. Correct implant failure –loosening or 
subsidence 
11. Correct implant failure - breakage 
12. Treat implant wear  
13. Treat osteolysis 
14. Treat implant corrosion 
15. Improve function 
16. Relieve pain 
 

 
 
 
 
 
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Table 2: Critical Aspects of Operative Procedure Requiring Presence of Experienced 
Surgeon 
 
 
Hemi-Arthroplasty 
• Trial component insertion and verification of hip stability 
• Implant insertion to ensure correct version 
• Cement procedure, if used 
• Final assessment of hip stability after implant insertion 
 
Total Hip Arthroplasty 
• Trial component insertion and verification of hip stability 
• Implant insertion to ensure correct alignment of femoral and acetabular 
components 
• Cement procedure, if used 
• Final assessment of hip stability after implant insertion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
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TABLE 3:  Sample Size Calculations Comparing Total Hip Arthroplasty (THA) and Hemi-
Arthroplasty (HA) 
 
A. Studies included in a meta-analysis comparing THA with HA for the outcome of re-
operation at one year 
 
Reoperation Rate 
Study 
THA 
HA 
van den Bekerom 2010 
5/110 
1/136 
Baker 2006 
4/36 
2/39 
Blomfeldt 2007 
4/56 
3/57 
Keating 2006 
6/63 
5/64 
Macaulay 2008 
1/16 
0/23 
THA vs. HA Combined Effect: fixed and random, relative risk = 1.67 (95% CI 0.86 to 3.24), 
p=0.13 
Pooled Event Rates:  THA fixed and random, incidence rate = 7.8% (95% CI 5.2 to 11.6) 
HA fixed, incidence rate = 5.3% (95% CI 3.2 to 8.9) 
HA random, incidence rate = 4.9% (95% CI 2.6 to 9.2) 
 
 
B. Sample size requirement for HEALTH Pivotal Trial [Non-Inferiority Design] 
 
 
 
 
 
 RRR = Relative Risk Reduction 
HA 1 yr event risk 
Total patients required 
Expected events 
RRR 
4% 
1123 
72 
0.50 
5% 
1316 
96 
0.45 
6% 
1435 
108 
0.42 

 
 
 
 
 
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Table 4: Functions of the Data Monitoring Committee (DMC) 
 
 
The DMC will function in an advisory rather than executive capacity and its duties will 
include the following:  
 
• Offering advice about the research protocol and proposals for data safety and monitoring, 
including statistical ‘warning rules’ for efficacy, safety and futility.  
 
• Evaluating the progress of the trial, including periodic assessments of data quality and 
timeliness, participant recruitment, accrual and retention, clinician adherence to the trial 
protocol and progress toward an orderly completion of the study.  
 
• Carrying out the rapid evaluation of serious unanticipated adverse events. 
 
• Evaluating pre-planned interim analyses for efficacy, safety, and the triggering of 
statistical warning rules.  When the DMC decides that a definitive answer to the trial 
question has been achieved (in terms of efficacy, safety, or futility) they will unblind the 
Principal Investigator. 
 
 
 
 
 

 
 
 
 
 
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 Figure 1: Anatomy of the Proximal Femur and Fracture Line Level 
 
 
 
                          
 
 
                           
 
Sub-capital
Mid-cervical
Basal
 
Femoral Neck Fracture 
Intertrochanteric Fracture 
Subtrochanteric Fracture 
      Intracapsular  
     Extracapsular  
      Sub-capital 
 
    Mid-cervical  
 
    Basi-cervical 

 
 
 
 
 
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Figure 2: Undisplaced and Displaced Femoral Neck Fractures 
 
 
 
 
     I   
          II                       III                   IV 
Undisplaced (I, II) and Displaced (III, IV) Femoral Neck Fractures

 
 
 
 
 
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Figure 3a. Unipolar Hemi-Arthroplasty Prosthesis 
 
 
 

 
 
 
 
 
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Figure 3b. Modular Unipolar Hemi-Arthroplasty Prosthesis 
 
 
 
 
Legend: 
A = Collar for neck to allow for the metal femoral head component 
B = Tapered neck to allow tight fit to metal femoral head component 
C-E = Metal stem of the femoral component 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
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Figure 3c. Bipolar Hemi-Arthroplasty Prosthesis 
 
 

 
 
 
 
 
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Figure 3d. Total Hip Arthroplasty Prosthesis 
 
 
 
 
 
 
 
  

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Figure 4: Conventional Randomized Controlled Trial 
 
Conventional randomized controlled trials typically randomize patients to one of two surgeries 
(A or B), and individual surgeons administer surgery A to some participants and surgery B to 
others.  
 
 
 
All health care providers involved in the trial will administer  
interventions A and B based on the randomization process 
 
 
Randomize Participants 
Intervention AA 
Intervention B 
 

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Figure 5: Expertise-Based Randomized Controlled Trial 
 
An alternative randomized controlled trial design randomizes participants to surgeons with 
expertise in surgery A who are committed to performing only surgery A or to surgeons with 
expertise in surgery B who are committed to performing only surgery B.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Potentially Eligible Patients 
With Displaced Femoral Neck Fractures 
Application of Eligibility Criteria 
(Met Eligibility Criteria) 
Surgeons with Threshold Level of 
Expertise  
In Total Hip Arthroplasty 
Surgeons with Threshold Level of 
Expertise  
In Hemi-Arthroplasty 
Outcome Assessments: 
Secondary Procedures and Function 
at 24 months 
Outcome Assessments: 
Secondary Procedures and Function 
at 24 months 
Threshold Expertise defined by: 
 
1) Total number of cases 
 
2) Cases in last year  

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Figure 6: Recruitment Procedures (Baseline Radiographs & Data Collection)  
 
Time Line 
 
Recruitment Procedures 
 
Data Collection 
 
Patient 
Identification  
 
•Direct referral within centre or between 
centres 
 
•None 
 
 
 
 
 
Eligibility 
Assessment 
•Study explanation  
•History-review, eligibility criteria, and 
other relevant medical conditions 
documented 
•Physical Examination 
•Radiographs  
 
•Informed Consent (if eligible) 
 
•Screening Form 
•Informed Consent 
•Patient Contact Form 
•Baseline Form 
•Fracture Characteristics Form 
•Pre-op Care Form 
 
 
 
 
 
 
Randomization •24-hour Internet randomization 
procedure 
•Eligibility criteria reviewed again 
•Key patient information recorded at 
Methods Centre 
•Allocation issued to patient  
•Entry Form at the Methods 
Centre 
 
 
 
 
 
 
Surgery 
•Either the total hip arthroplasty or hemi-
arthroplasty surgical protocols followed 
by a surgeon with expertise in the 
procedure 
•Surgical Report Form 
•Surgical PD Form 
•AE Form 
 
 
 
 
 
Peri-operative 
Care within 48 
hours post 
surgery 
•Standardization of key aspect of peri-
operative care             
•Radiographs  
•Peri-operative Form  
•Post-op Care Form 
•RS, AE Forms 
 
 
 
 
 

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Figure 7: Post-Surgery Follow-Up Procedures 
 
 
Time Line 
Outcome Events  
Assessment Procedures
 
Data Collection 
1 week  
(24 hrs –  
10 days 
window) 
In Person/  
Hospital/Clinic 
(if prior to D/C) 
•Follow-up Form  
•SP, AE Forms  
•SF-12, WOMAC, EQ-5D (self-administered*)  
 (asking about patient function prior to surgery) 
 
 
 
10 weeks 
(8-12 weeks 
window) 
 
In Person/ 
Hospital/Clinic 
 (if prior to D/C) 
or Telephone  
•Follow-up Form, and TUG Test 
•SP, AE Forms  
•SF-12, WOMAC, EQ-5D (self-administered*)  
•Radiographs  
 
 
 
6 months  
(5-7 months 
window) 
In Person/ 
Hospital/Clinic 
or Telephone 
•Follow-up Form, and TUG Test  
•SP, AE Forms  
•SF-12, WOMAC, EQ-5D (self-administered*) 
 
 
 
9 months 
(8-10 months 
window) 
Telephone  
or In Person/ 
Hospital/Clinic 
•Follow-up Form 
•SP, AE Forms  
•SF-12, WOMAC, EQ-5D (interview-administered) 
 
 
 
12 months  
(11-13 months 
window) 
In Person/ 
Hospital/Clinic 
or Telephone 
•Follow-up Form, and TUG Test  
•SP, AE Forms 
•SF-12, WOMAC, EQ-5D (self-administered*)  
•Radiographs 
 
 
 
18 months  
(17-19 months 
window) 
Telephone 
or In Person/ 
Hospital/Clinic 
•Follow-up Form  
•SP, AE Forms  
•SF-12, WOMAC, EQ-5D (interview-administered) 
 
 
 
24 months  
(>24 months 
window) 
In Person/ 
Hospital/Clinic 
or Telephone 
•Follow-up Form, and TUG Test  
•SP, AE Forms  
•SF-12, WOMAC, EQ-5D (self-administered*)  
•Radiographs 
•Planned RS after 24 months 
* Prepare for interview-administered data collection if patient unable to complete self-administered 
forms. 
 
AE = Adverse Event, D/C = Discharge, EQ-5D = EuroQol-5D, SP = Secondary Procedures, SF-12 = 
Short Form-12, TUG = Timed Up and Go, WOMAC = Western Ontario McMaster Osteoarthritis Index. 
 
 
 

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Figure 8: Limiting Loss to Follow-Up 
 
1. We will exclude individuals who are likely to present problems with follow-up (see 
exclusion criteria).  
 
 
2. At the time of randomization, as well as their own address and phone number, each 
patient will provide the name and address of their primary care physician, and the name, 
address and phone number of three people at different addresses with whom the patient 
does not live who are likely to be aware of the patient’s whereabouts. The research 
coordinator will confirm that these numbers are accurate prior to the patient’s discharge 
from hospital.   
 
 
3. Participants will receive information on hip fractures, their complications and the 
potential treatment effects, expectations for personal benefit from study participation, and 
motivation for adherence with follow-up visits and research protocols.  Aids used for 
education and support will include a patient information booklet, a toll free telephone 
number/pager (24 hour) for advice in case of complications or questions regarding follow-
up visits, and an Internet site for “commonly asked questions” for research investigators 
with patients enrolled in the study (www.ihfrc.ca).   
 
 
 
4. Patients will receive reminders for upcoming clinic visits from local study personnel.   
 
 
 
 
5. Follow-up schedules will coincide with normal surgical fracture clinic visits.   
 
 
 
6. Study personnel will contact patients no less frequently than once every six months to 
maintain contact and obtain information about any planned change in residence.   
 
 
 
7. If a patient refuses to return for a follow-up assessment, study personnel will determine 
his/her status with regard to secondary procedures or any secondary outcome by phone 
contact with the patient, alternate contact, or the patient’s family physician. 
 
Reference:  
 
 
 
 
 
 
Sprague S, Leece P, Bhandari M, Tornetta P, Schemitsch E, Swiontkowski M, SPRINT 
Investigators.  Limiting loss to follow up in a multicentre randomized controlled trial in 
orthopaedic surgery.  Controlled Clinical Trials. 2003;24:719-725. 

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Appendix 1: Schedule of Events Requiring Radiographs and Data Forms  
 
Radiographs & 
Event Forms 
 
Pre-Surgery 
 
Surgery 
 
Screening 
 
Enrollment 
 
Baseline 
 
(Day 0) 
< 48 hrs 
Post 
Surgery 
 
D/C 
1 wk 
(24 hrs 
-10 ds) 
10 wk 
(8-12 
wks) 
6 mo 
(5-7 
mos) 
9 mo 
(8-10 
mos) 
12 mo 
(11-13 
mos) 
18 mo 
(17-19 
mos) 
24 mo 
(≥24 
mos) 
Radiographs 
 
 
● 
 
● 
 
 
● 
 
 
● 
 
● 
Screening  
● 
 
 
 
 
 
 
 
 
 
 
 
 
Informed 
Consent 
 
● 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
● 
 
 
 
 
 
 
 
 
 
 
 
Baseline  
 
 
● 
 
 
 
 
 
 
 
 
 
 
Patient Contact  
 
● 
 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Surgical Report  
 
 
 
● 
 
 
 
 
 
 
 
 
 
Post-Op Care  
 
 
 
 
● 
 
 
 
 
 
 
 
 
Clinic or 
Telephone  
Follow-Up 
 
 
 
 
 
 
● 
● 
● 
● 
● 
● 
● 
Secondary 
Procedure 
 
 
 
 
* 
 
* 
* 
* 
* 
* 
* 
* 
AE 
 
 
 
* 
* 
 
* 
* 
* 
* 
* 
* 
* 
TUG 
 
 
 
 
 
 
● 
● 
● 
 
● 
 
● 
SF-12 
 
 
 
 
 
 
● 
● 
● 
● 
● 
● 
● 
WOMAC 
 
 
 
 
 
 
● 
● 
● 
● 
● 
● 
● 
EQ-5D 
 
 
 
 
 
 
● 
● 
● 
● 
● 
● 
● 
Missed  
Follow-Up 
 
 
 
 
 
 
* 
* 
* 
* 
* 
* 
 
Early W/D 
 
 
 
 
 
 
* 
* 
* 
* 
* 
* 
* 
* Complete forms when and/or if applicable.