Randomized Trial of a Multifactorial Fall Injury Prevention Strategy
Phase: PHASE3
Conditions: Accidental Falls, Wounds and Injuries
Sponsor: Brigham and Women's Hospital

 
 
 
 
TITLE:  RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
STUDY PROTOCOL 
COMMUNICATING PI:  
 
SHALENDER BHASIN, MD 
JOINT PIS: 
 
 
 
THOMAS GILL, MD; DAVID B. REUBEN, MD 
 
APPLICANT CONSORTIUM: 
THE PEPPER CENTERS CONSORTIUM FOR PREVENTION OF 
SERIOUS FALL-RELATED INJURIES 
FUNDING AGENCIES: 
 
NATIONAL INSTITUTE ON AGING AND PCORI 
NIA GRANT NUMBER: 
 
UO1AG0 48270 
NCT NUMBER:  
 
NCT02475850 
APPLICANT ORGANIZATION: 
BRIGHAM AND WOMEN’S HOSPITAL 
DATE OF INITIAL IRB APPROVAL: APRIL 30, 2015 
VERSION DATE: 
 
 
December 31, 2019 
VERSION NUMBER:  
 
2.8 
 
 

RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
 
Summary of Changes from Protocol Version 2.1 to Version 2.2 
 
In addition to corrections to typographical errors and spelling mistakes, the following changes were made to 
convert version 2.1 to version 2.2: 
 
1. Eliminate the postal questionnaire to ascertain fall/fall injury data.  Instead, obtain these data through 
telephone calls from the RAC to all participants.  (Note:  all STRIDE participants will continue to use the fall 
calendars as a memory aid). 
 
2. Change the timing of follow-up calls to patients to inquire about falls/fall injuries from every 3 months to 
every 4 months. 
 
3. To comply with Pennsylvania state law, the list of people who are eligible to serve as proxy respondents for 
people who are unable to provide informed consent due to cognitive or hearing impairment has been adjusted. 
 
Summary of Changes from Protocol Version 2.2 to 2.3 
 
1. Changed the lower age limit for eligibility from 75 to 70. 
 
Summary of Changes from Protocol Version 2.3 to 2.4 
 
2. Clarification to the Adjudication process with CMS 
 
Summary of Changes from Protocol Version 2.4 to 2.5 
 
1. Duration of the study changed from 36 months (18 months of recruitment and 18 months of follow-up) to 
40 months (20 months of recruitment and minimum 20 months of follow-up). 
2. Target sample size adjusted to n = 5,322 for a 40-month study instead of n = 6000 for a 36-month study. 
3. Interim monitoring was changed from efficacy and futility to efficacy or futility, if necessary.  
Summary of Changes from Protocol Version 2.5 to 2.6 
1. The definition of the primary outcome has been modified to reflect the recommendations of the DSMB 
working group 
Summary of Changes from Protocol Version 2.6 to 2.7 
1. Extend the study from a minimum of 20 and maximum of 40 months follow-up to a minimum of 24 and 
maximum of 44 months of follow-up. Final end date of the study, including the analytic phase is now 
extended to April 30 2020. 
Summary of Changes from Protocol Version 2.7 to 2.8 
1. Addition of new and updated information to the description of the statistical analysis plan in the protocol 
document. 
 
 
 

RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
 
 
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STUDY SUMMARY FOLLOWS 
Title 
RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY 
PREVENTION STRATEGY 
Study Design 
The design is a cluster randomized, parallel group superiority trial with 
practices stratified by healthcare system and patients nested within 
practices.  The unit of randomization is the practice. 
Study Duration 
5 years 
Trial Sites 
10 trial sites: The Partners’ Health Care System; Essentia; Hopkins 
Health Care System; HealthCare Partners; Reliant Health Care 
System; Mount Sinai Health Care System; University of Pittsburgh 
Health Care System; University of Texas Medical Branch Health Care 
System; University of Iowa Health Care System; University of Michigan 
Health Care System.      
Objective 
Conduct a cluster-randomized trial to determine the effectiveness of an 
evidence-based, patient-centered multifactorial fall injury prevention 
strategy.  
Number of Subjects 
The original target sample size was 6,000 participants enrolled from 86 
practices to provide 90% power to detect a 20% reduction in the rate of 
the primary outcome with intervention relative to control. Later, the 
duration of the trial was extended to a total of 40 months (20 months of 
recruitment and an additional 20 months of follow-up), which reduced 
the target sample size to 5,322 participants.  Recruitment ended after 
20 months on March 31, 2017, with a total of 5,451 participants 
enrolled.  
Main Inclusion 
Criteria 
Community-living persons, 70 years or older, who are at increased risk 
for serious fall injuries.  
Intervention 
An evidence-based patient-centered intervention that will combine 
elements of a multifactorial, risk factor-based, standardly-tailored fall 
prevention strategy developed at Yale, practice guidelines offered by 
the CDC's "STEADI" toolbox and the joint American Geriatrics 
Society/British Geriatrics Society guidelines, and ACOVE practice 
change approach. 

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Duration of 
Intervention 
A minimum of 20 months and a maximum of 40 months. 
Primary Outcome 
The primary outcome is serious fall injuries, operationalized as a fall 
resulting in:   (1) (fracture other than thoracic/lumbar vertebral; joint 
dislocation; or cut requiring closure) AND any medical attention; OR (2) 
(head injury; sprain or strain; bruising or swelling; or other) requiring 
hospitalization.  
Primary Analysis 
The risk of any serious fall injury (i.e., time to first event) will be 
analyzed using a survival model that incorporates competing risks (due 
to death) and clustering. In this analysis, participants who are lost to 
follow-up without a prior serious fall-related injury will be censored at 
their date last seen. In a secondary analysis, we will adjust for the pre-
specified set of baseline covariates to examine their influence on the 
intervention effect. 
Secondary 
Outcomes 
Number of falls, number of all fall injuries, and measures of well-being.  
Adaptive 
Components 
Adaptive components of the trial include: 1) monitoring the accrual 
rate to determine whether the study eligibility criteria need to be 
reconsidered if recruitment is lower than expected, taking into account 
that any changes could affect the inferences; 2) monitoring the potential 
for ascertainment bias because of interactions between the FCMs and 
study participants and changing the primary outcome definition if 
necessary; 3) monitoring the primary outcome rate to determine 
whether the outcome needs to be adapted, e.g., from time to first 
serious fall-related injury to time to all recurrent serious fall-related 
injuries if the former rate is too low, affecting the power of the study;  4) 
interim monitoring for efficacy or futility, if necessary; and 5) refining the 
analytic methods based on the validity of the assumptions; such an 
adaptation will be done blinded to treatment, e.g., if the death rate is 
low, competing risks could be considered as a secondary, rather than a 
primary, analysis. 
Interim Analysis 
Interim monitoring will focus on patient accrual, baseline comparability 
of treatment groups, protocol adherence, data completeness and 
quality, accrual of fall events, safety, and efficacy or futility. 

RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
 
 
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ABBREVIATIONS 
ACOVE 
 
Assessing Care of Vulnerable Elders Project 
AE 
 
 
Adverse Event 
AGS 
 
 
American Geriatrics Society 
AHRQ  
 
Agency for Healthcare Research & Quality 
BGS 
 
 
British Geriatrics Society 
CAT 
 
 
Computer Adaptive Testing 
CDC 
 
 
Centers for Disease Control and Prevention 
CDRN  
 
Clinical Data Research Network 
CTSA  
 
Clinical Translational Science Award 
CCFP  
 
Connecticut Collaborative Falls Program 
CMS  
 
Centers for Medicare and Medicaid Services 
CPMC  
 
Central Project Management Center 
D & I  
 
Dissemination and Implementation 
DCC 
 
 
Data Coordinating Center 
DE 
 
 
Design Effect 
DSMB  
 
Data and Safety Monitoring Board 
DSMP  
 
Data and Safety Monitoring Plan 
EDC 
 
 
Electronic Data Capture 
EHR 
 
 
Electronic Health Record 
EMR  
 
Electronic Medical Record 
FCS 
 
 
Falls Care Software 
FCM 
 
 
Falls Care Manager 
FICSIT  
 
Frailty and Injury Cooperative Studies of Intervention Technologies 
FRID   
 
Fall Risk Increasing Drug 
FES 
 
 
Falls Efficacy Scale 
GCP 
 
 
Good Clinical Practice 
HIPAA  
 
Health Insurance Portability and Accountability Act 

RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
 
 
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ICC 
 
 
Intracluster Correlation  
ICF 
 
 
Informed Consent Form 
ICH 
 
 
International Conference on Harmonization 
IT 
 
 
Information Technology 
ITS 
 
 
Information Technology Services 
LIFE 
 
 
Lifestyle Interventions and Independence for Elders 
LPSC  
 
Local Patients and Stakeholders Council 
LL-FDI  
 
Late Life Function and Disability Instrument 
MAR  
 
Missing at Random 
MMSE  
 
Mini-Mental State Examination 
MOP  
 
Manual of Procedures 
MSO  
 
Medical Safety Officer 
NP 
 
 
Nurse Practitioner 
NPSC  
 
National Patients and Stakeholders Council 
OAC 
 
 
Outcomes Adjudication Committee 
OAIC  
 
Claude D. Pepper Older Americans Independence Centers 
OHRP  
 
Office of Human Research Protections 
OT 
 
 
Occupational Therapist 
PCORI  
 
Patient-Centered Outcomes Research Institute 
PCORTF 
 
Patient-Centered Outcomes Research Trust Fund 
PCP 
 
 
Primary Care Provider 
PDC 
 
 
Publications and Dissemination Committee 
PHI 
 
 
Personal Health Information 
PPRN  
 
Patient Powered Research Network 
PreFIT  
 
A Fall Injury Prevention Trial in the UK 
ProFaNE 
 
Prevention of Falls Network Europe 
PROMIS 
 
Patient Reported Outcomes Measurement Information System 
PVQ 
 
 
Pre-visit Questionnaire  

RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
 
 
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PT 
 
 
Physical Therapist 
RAC 
 
 
Recruitment and Assessment Center 
RCT 
 
 
Randomized Clinical Trial 
RN 
 
 
Registered Nurse 
SAE 
 
 
Serious adverse event 
SAP 
 
 
Statistical Analysis Plan 
SAS 
 
 
Statistical Analysis System 
SPPB  
 
Short Physical Performance Battery 
STEADI 
 
Stopping Elderly Accidents, Deaths, and Injuries 
STRIDE 
 
Strategies to Reduce Injuries and Develop Confidence in Elders 
UP 
 
 
Unanticipated Problem 
VA 
 
 
Veterans Administration 
 
 

RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
 
 
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CONTENTS 
1. INTRODUCTION ............................................................................................................................................ 10 
2. STUDY OBJECTIVES .................................................................................................................................... 10 
3. BACKGROUND ............................................................................................................................................. 11 
4. STUDY DESIGN ............................................................................................................................................. 11 
4.1 NUMBER OF SUBJECTS ................................................................................................................................................................................... 13 
4.2 SUBJECT SELECTION AND WITHDRAWAL .................................................................................................................................................. 13 
4.2.1 Inclusion and Exclusion Criteria ........................................................................................................................................................... 13 
4.3 SCREENING, RECRUITMENT, AND ENROLLMENT ...................................................................................................................................... 13 
4.3.1 Screening .......................................................................................................................................................................................................... 13 
4.3.2 Recruitment and Enrollment .................................................................................................................................................................. 14 
4.3.3 Patients with Cognitive Impairment ................................................................................................................................................... 15 
4.3.5 Early Withdrawal of Participants ........................................................................................................................................................ 15 
5. STUDY INTERVENTION ................................................................................................................................ 15 
5.1 ACTIVITIES PRIOR TO INITIAL VISIT ........................................................................................................................................................... 16 
5.2 ACTIVITIES DURING AND IMMEDIATELY AFTER INITIAL VISIT.............................................................................................................. 16 
5.3 ACTIVITIES AFTER INITIAL VISIT AND BETWEEN VISITS ........................................................................................................................ 17 
6. CONTROL INTERVENTION .......................................................................................................................... 18 
6.1 ACTIVITIES AFTER SCREENING .................................................................................................................................................................... 18 
6.2 ACTIVITIES CONDUCTED AT THE SITES ...................................................................................................................................................... 18 
6.2.1 Rationale .......................................................................................................................................................................................................... 18 
7. OUTCOME MEASURES ................................................................................................................................ 18 
7.1 DEFINITION AND ASCERTAINMENT OF OUTCOMES .................................................................................................................................. 18 
7.1.1 Fall-Related Outcomes ............................................................................................................................................................................... 19 
7.1.2 Well-Being Outcomes (assessed by phone at baseline, 12m, and 24m in random sample of 720 participants 
enrolled in first 12 months) ................................................................................................................................................................................ 20 
7.1.3 Tertiary Outcomes ....................................................................................................................................................................................... 21 
8. STUDY PROCEDURES AND VISITS ............................................................................................................ 21 
8.1 RANDOMIZATION ........................................................................................................................................................................................... 21 
8.2 SCHEDULE OF EVENTS ................................................................................................................................................................................... 22 
9. STATISTICAL ANALYSIS, SAMPLE SIZE AND POWER CALCULATIONS ............................................... 23 
9.1 DESIGN OVERVIEW ........................................................................................................................................................................................ 23 
9.2 SUBJECT ALLOCATION TO TREATMENT ARMS .......................................................................................................................................... 23 
9.3 SAMPLE SIZE ................................................................................................................................................................................................... 23 
9.5 INTERIM MONITORING .................................................................................................................................................................................. 25 
9.6 STATISTICAL ANALYSIS PLAN ...................................................................................................................................................................... 25 
10. DATA MANAGEMENT ................................................................................................................................. 26 
10.1 FIELD OPERATIONS SUPPORT ................................................................................................................................................................... 27 
10.1.1 Screening ....................................................................................................................................................................................................... 27 
10.1.2 Baseline Interviews ................................................................................................................................................................................... 27 
10.1.3 Outcome Surveillance .............................................................................................................................................................................. 27 
10.2 WEBSITE TOOLS .......................................................................................................................................................................................... 27 
10.2.1 STRIDE Portal (stridestudy.org) ........................................................................................................................................................ 27 
10.2.2 Screening Support ..................................................................................................................................................................................... 27 
10.2.3 Adjudication Support ............................................................................................................................................................................... 27 
10.2.4 Intervention Support ............................................................................................................................................................................... 28 
10.3 ADMINISTRATIVE TRACKING APPLICATION ........................................................................................................................................... 28 
10.4 THE DATA MART ......................................................................................................................................................................................... 28 

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10.5 DATA SECURITY ........................................................................................................................................................................................... 28 
10.6 PROTECTION FROM DATA LOSS AND DOWNTIME ................................................................................................................................. 28 
11. SAFETY AND ADVERSE EVENTS ............................................................................................................. 29 
11.1 BACKGROUND ............................................................................................................................................................................................... 29 
11.2 DEFINITIONS ................................................................................................................................................................................................ 29 
11.3 RESPONSIBILITIES ....................................................................................................................................................................................... 30 
11.4 LEVEL OF MONITORING IN THIS STUDY ................................................................................................................................................... 30 
11.5 ASCERTAINMENT OF AE, UNANTICIPATED PROBLEMS (UP), AND SAE ........................................................................................... 31 
11.5.1 Adverse events............................................................................................................................................................................................. 31 
11.5.2 Unanticipated Problems (UP) .............................................................................................................................................................. 31 
11.5.3 Ascertainment of SAEs and Deaths ................................................................................................................................................... 31 
11.6 SAFETY PERSONNEL .................................................................................................................................................................................... 32 
12. ETHICAL AND REGULATORY CONSIDERATIONS .................................................................................. 32 
12.1 GOOD CLINICAL PRACTICE STATEMENT .................................................................................................................................................. 32 
12.2 INFORMED CONSENT .................................................................................................................................................................................. 32 
12.3 INSTITUTIONAL REVIEW BOARD .............................................................................................................................................................. 33 
12.4 PROTOCOL AMENDMENTS ......................................................................................................................................................................... 34 
12.5 RISKS TO HUMAN SUBJECTS ...................................................................................................................................................................... 34 
12.5.1 Protection Against Risks ........................................................................................................................................................................ 34 
12.5.2 Potential Benefits of the Proposed Research to Human Participants and Others ...................................................... 34 
12.5.3 Importance of the Knowledge to be Gained .................................................................................................................................. 35 
12.6 SAFETY MONITORING PROTOCOL ............................................................................................................................................................. 35 
12.7 INCLUSION OF WOMEN AND MINORITIES ............................................................................................................................................... 35 
13. STUDY DOCUMENTS ................................................................................................................................. 36 
13.1 RETENTION OF RECORDS ........................................................................................................................................................................... 36 
14. PUBLICATION AND DISSEMINATION POLICY ........................................................................................ 36 
14.1 DISSEMINATION ........................................................................................................................................................................................... 36 
15. ORGANIZATIONAL FRAMEWORK OF AN INTERDISCIPLINARY TEAM OF INVESTIGATORS, 
PATIENTS, AND STAKEHOLDERS ................................................................................................................. 37 
15.1 COMMITTEES ................................................................................................................................................................................................ 37 
15.2 REPORTING STRUCTURE ............................................................................................................................................................................ 37 
15.3 MEETING SCHEDULE AND FUNCTIONS OF THE LEADERSHIP ............................................................................................................... 38 
15.4 ADDITIONAL COMMITTEES ........................................................................................................................................................................ 39 
15.5 INTEGRATION OF PATIENT AND STAKEHOLDERS IN THE TRIAL’S PLANNING, IMPLEMENTATION, ANALYSES AND 
DISSEMINATION ..................................................................................................................................................................................................... 39 
15.5.1 Local Patient and Stakeholder Councils ......................................................................................................................................... 40 
15.5.2 National Patient and Stakeholder Council .................................................................................................................................... 41 
15.5.3 Training patients, stakeholders, and investigators ................................................................................................................... 41 
15.5.4 Engaging patients and other stakeholders as partners in all phases of the research: ............................................. 41 
15.5.5 Eliciting patients’ and stakeholders’ voices through focus groups .................................................................................... 42 
15.5.6 Monitoring the study’s progress ......................................................................................................................................................... 42 
15.5.7 Dissemination and implementation of study findings .............................................................................................................. 42 
15.5.8 Ongoing Evaluation and Feedback ................................................................................................................................................... 42 
 
 

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1. INTRODUCTION 
This document is a protocol for a human research study to be conducted according to US and international 
standards of Good Clinical Practice (FDA Title 21 part 312 and International Conference on Harmonization 
guidelines), applicable government regulations, and institutional research policies and procedures.  
2. STUDY OBJECTIVES 
 
The proposed multi-site randomized clinical trial will determine the effectiveness of an evidence-based, 
multifactorial patient-centered intervention to reduce the risk of serious fall injuries among non-institutionalized 
older persons. The project is a collaboration among investigators, patients, and other key stakeholders from 
the 14 Claude D. Pepper Older Americans Independence Centers (OAICs) and 10 healthcare systems where 
patients will be recruited.  The OAIC investigators bring decades of research experience in developing, 
implementing, and testing interventions to treat and prevent complex geriatric conditions, including falls. The 
patients and stakeholders bring their unique personal perspective of how falls and fall injuries affect their lives, 
the difficulties they face in adhering to interventions, what outcomes are important to them, and what attributes 
of the interventions render them feasible, scalable, and sustainable. The clinical sites bring participants, clinical 
environments, and expertise in patient-centered research and implementation.  The investigators, patients, and 
other stakeholders planned and prepared this proposal jointly; these partners will continue to be collaboratively 
engaged in all aspects of the trial’s implementation.  
Our integrated strategy to reduce serious fall injuries, guided by continuous input from our patient advisors and 
stakeholders during conference calls and focus groups, encompasses several patient-centered components, 
including screening to identify persons at high risk for falls and injuries, assessing high risk individuals to define 
their risk factors, individualized intervention based on each person’s risk factors, and intervening to implement 
appropriate care processes and behavioral changes. Because the contributors to fall injuries are multifactorial, 
the proposed interventions to reduce serious fall injuries also comprise multiple components, including:   
 
Changing organizational and provider behavior (quality improvement through ACOVE-2 practice 
redesign model) to initiate care processes, based on an individual patient’s identified risk factors; 
 
Treating or mitigating medical and environmental risk factors specific to each individual (e.g., orthostatic 
hypotension, multiple medications, visual impairment, foot problems, hazards at home); 
 
Providing exercise and rehabilitation interventions (e.g., physical therapy and community-based 
multimodality exercise programs) tailored to the participant’s physical and cognitive ability, to improve 
balance, gait, and other motor functions; 
 
Reducing the risk of injury if person does fall (e.g., osteoporosis treatment; preventing long lie after a 
fall); 
 
Patient engagement throughout the trial’s implementation, including ascertainment of individual goals, 
and patient activation based on successful approaches developed at Yale to prevent falls and injuries. 
 
Accordingly, we will conduct a randomized trial to determine the effectiveness of an evidence-based, 
intervention that will combine elements of ACOVE-2 practice redesign, a multifactorial, individually-tailored 
intervention developed at Yale, and practice guidelines offered by the CDC's "STEADI" toolbox and the joint 
American Geriatrics Society/British Geriatrics Society guidelines, and will utilize a cluster randomization 
strategy for participant allocation. The primary outcome is serious fall injuries operationalized as a fall resulting 
in: (1) (fracture other than thoracic/lumbar vertebral; joint dislocation; or cut requiring closure) AND any medical 
attention; OR (2) (head injury; sprain or strain; bruising or swelling; or other) requiring hospitalization. The trial 
originally had a slightly different primary outcome definition. The first primary outcome definition will be 
explored as a secondary outcome as explained below. The definition was changed based on the 
recommendation of a DSMB working group.  Secondary outcomes, based on input from patients and 
stakeholders, include all injurious falls and all falls regardless of injury. The pre-existing operationalized 
primary outcome which was “a fall resulting in (fracture other than thoracic/lumbar vertebral; joint dislocation; or 

RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
 
 
11
cut requiring closure; head injury; sprain or strain; bruising or swelling; or other) AND any medical attention” is 
now a secondary outcome. Other secondary outcomes are indicators of well-being, including fall efficacy, 
physical function and disability, anxiety, and depressive symptoms.  
Collaboratively, the investigators, patient advisors, and stakeholders will accomplish the following Specific 
Aims: 
1. To conduct in partnership with patients and stakeholders a cluster randomized trial of the intervention 
in a sample of 5322 participants from 86 practices in 10 health care systems that reflect geographic 
and sociodemographic diversity.  The trial will include features of an adaptive design, to facilitate 
“learning”, including a pre-specified, mid-term analysis. 
2. To identify and evaluate jointly with patients and stakeholders the obstacles and facilitators of the post-
trial scalability, sustainability, and dissemination of the fall injury prevention strategy. 
3. BACKGROUND 
Approximately one in three older Americans falls each year and 20-30% of those who fall suffer moderate to 
severe injuries such as lacerations, hip fractures, or head trauma.1,2  The problem is important particularly 
among those 75 years and older when the incidence of falls rises dramatically.3  Among older adults, falls are 
the leading cause of both fatal and nonfatal injuries. In 2010, 2.3 million nonfatal fall injuries were treated in 
emergency departments and more than 662,000 of these patients were hospitalized.4  These numbers will rise 
with the aging of the baby boomers.  In addition, many who do not sustain injuries develop fear of falling,5 
which may result in self-limiting their activities, leading to reduced mobility and loss of physical fitness, further 
increasing their risk of falling.6 
Despite decades of research that has demonstrated conclusively that many falls in the elderly can be 
prevented,7-10 quality of care for falls remains low.  Fewer than half of those who fall each year discuss their 
falls or fall prevention with a health care provider.11  Moreover, only a third of elderly patients in primary care 
practice are screened for falls and the quality of care for those who are at risk for falling has not improved in 
the past decade.12,13 
Accordingly, this project funded jointly by the National Institute on Aging and the Patient Centered Outcomes 
Research Institute (PCORI) is a multi-site cluster randomized clinical trial (RCT) of an evidence-based, 
multifactorial individually-tailored intervention to reduce the risk of serious fall injuries among non-
institutionalized older persons.  
4. STUDY DESIGN 
The proposed trial is a cluster-randomized, parallel group superiority trial with practices stratified by healthcare 
system and patients nested within practices. The unit of randomization is the practice. This avoids the potential 
for contamination of controls, allows staff to be trained efficiently, and improves the feasibility of applying the 
intervention practice-wide. The primary outcome is time to first serious fall injury assessed at the patient level. 
This outcome was selected as primary because the initial event is associated strongly with subsequent 

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adverse outcomes14 regardless of the occurrence of another event; however, all serious fall injuries will be 
evaluated in a supportive analysis.  
Adaptive features will include:  
1. Monitoring the accrual rate to determine whether the eligibility criteria should be altered if enrollment is 
lower than expected (e.g., by lowering the age entry criterion); 
2. Monitoring the potential for ascertainment bias and changing the primary outcome definition if 
necessary 
3. Monitoring the primary outcome rate to determine whether the outcome needs to be adapted, e.g., from 
first serious fall injury to all serious fall injuries if the former rate is too low, affecting the power of the 
study; 
4. Interim monitoring for efficacy or futility, if necessary; and  
5. Refining the analytic methods (blinded to treatment) based on the validity of the assumptions (e.g., 
models that consider non-proportional hazards).  Because the recruitment period will be relatively short, 
other commonly used adaptive features are not feasible, such as adapting the randomization, 
intervention or sample size (based on nuisance parameters (e.g., intracluster correlation [ICC] and/or 
observed treatment effect).15 
 
 

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4.1 Number of Subjects 
The original protocol had planned for randomization of 80+ practice sites – each randomizing an average of 75 
participants, for a total of 6,000 randomized participants in a study of 36 months duration (18 months of 
recruitment and a further 18 months of follow up).  Later, the duration of the trial was extended to a total of 40 
months (20 months of recruitment and a minimum 20 months of follow-up), which reduced the target sample 
size to 5,322 participants.  Recruitment ended after 20 months on March 31, 2017, with a total of 5,451 
participants enrolled.  
4.2 Subject Selection and Withdrawal 
4.2.1 Inclusion and Exclusion Criteria 
Table 1 lists the inclusion and exclusion criteria for screening patients for participation in the trial. 
Because participants must be able to provide consent (or assent) over the phone, it is not feasible to enroll 
participants who do not speak English or Spanish.  
4.3 Screening, Recruitment, and Enrollment 
Our procedures have been designed to maximize efficiency and have been vetted with our stakeholders. As 
described in Human Subjects, we are committed to enrolling ethnic minorities and disadvantaged populations, 
including those for whom Spanish is their primary language. 
4.3.1 Screening 
From each practice, patients aged 70 or older will be identified via the electronic health record (EHR) and 
subsequently screened to identify those at increased risk for falls and fall-related injuries.  Based on our pilot 
testing, the primary strategy will be centralized screening.  The clinic sites will provide the Yale Recruitment 
and Assessment Center (RAC) with the names and addresses of patients in the practice who are aged 70 
years or over.  These people will be sent a letter addressed from their primary providers asking them to 
Table 1: Inclusion and Exclusion Criteria 
Inclusion Criteria 
i. 
The patient is at least 70 years of age. 
ii. 
The patient must answer ‘yes’ to one or more of the following questions: 
ii.a Have you fallen and hurt yourself in the past year? 
ii.b Have you fallen 2 or more times in the past year? 
ii.c Are you afraid that you might fall because of balance or walking problems? 
Exclusion Criteria 
i. 
The patient is enrolled in hospice.  
ii. 
The patient resides in a nursing home. 
iii. 
The patient is not capable of providing informed consent (or assent), and a proxy is not 
available. 
iv. 
The patient does not speak English or Spanish 

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14
complete the fall screening questionnaire, which will include the three questions in Table 1, and mail it back to 
the RAC.  If needed, a second mailing may be sent out to non-responders to improve response rates. 
To allow some flexibility, we will also use a clinic screening strategy, as needed.  Practice staff will screen all 
age-eligible patients during routine primary care visits.  Those responding positively to any of the 3 screening 
questions in Table 1 will be deemed to have “screened in” and will be recruited into the study.  As part of a 
practice change, the screening questions will be imbedded in the usual work flow, as a part of standard vital 
signs.  This approach has been implemented successfully in Assessing Care of Vulnerable Elders (ACOVE) 
program,16-18 and was successfully pilot-tested during Year 1 at practices across each of the 10 clinical sites. 
During the trial, the age of eligibility was lowered from 75 to 70 to expand our pool of eligible patients. Based 
on data available from the Center for Disease Control injury data and other studies, the reduction in the 
outcome rate will likely be relatively modest for ages down to 72, and this reduction will be obviated, at least in 
part, by the need to meet one or more of the three fall-injury screening criteria.8,19,20   We will implement the 
enrollment of people with a lower age eligibility age in steps.  EHR data will be obtained for people aged 70 
and above.  The study team will proceed to screen patients who are 74 years or older. The study team will 
monitor the impact of lowering the eligibility age to 74 on the recruitment pool, recruitment yield, and the 
proportion of patients enrolled based solely on the “fear of falling” criterion. If the study team determines that 
further lowering of the age criterion is required, the study team will request Steering Committee’s approval, 
based on its evaluation of the afore mentioned monitoring results. While it is unlikely that we would need to 
enroll participants younger than 72, the age of eligibility was lowered to 70 to allow efficient enrollment if 
needed. 
The screening questions were selected based on evidence indicating that persons meeting these criteria are at 
significantly elevated risk for injurious falls.8,19 Evidence from the ACOVE prime study suggests that nearly 
40% of persons aged 75 or older screen positive for any one of screening questions.17 Comparable results 
were obtained during our pilot testing. 
4.3.2 Recruitment and Enrollment  
For the centralized screening strategy, patients who screen positive will be sent a recruitment packet.  For the 
clinic screening strategy, screen-positive patients will be handed (or mailed) the recruitment packet. For each 
strategy, the recruitment packet will include an invitation letter from their primary provider and an information 
sheet about the study. The letter will indicate that they can opt out from being contacted about the study by 
returning a self-addressed, pre-stamped postcard to the RAC within two weeks.   
Screen-positive patients in both intervention and control practices who do not opt out will be called by a study 
staff member at the RAC. During this telephone interview, the recruiter will confirm the absence of any 
exclusion criteria, review the purpose of the study, answer any questions and, after obtaining verbal consent, 
collect baseline data on: key demographic characteristics – including ethnicity, marital status, living situation, 
and educational attainment; a cognitive screen using the Callahan 6-item screener;21 health insurance and 
other PHI; chronic conditions; fall history; self-rated health; height and weight; functional status; and other 
secondary outcomes (among a random subset of 720 participants based on our sample size estimates). 
Screen-positive patients will be recruited until the desired number (average n=75) has been enrolled in each 
practice.  
Because randomization of practices will occur prior to participant enrollment, it will be important to minimize 
any potential bias due to lack of allocation concealment.  The central recruitment staff will be kept blinded to 
randomization status of the practices and will be rigorously trained to reduce potential bias.  Although practice 

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15
staff cannot be kept blinded to intervention status, we will carefully monitor performance at practices that 
implement clinic screening to ensure that all age-eligible patients are screened for fall risk. 
4.3.3 Patients with Cognitive Impairment 
Patients with cognitive impairment will be included in the study because: (1) cognitive impairment is a risk 
factor for fall injuries;22 (2) patients with cognitive impairment may benefit from several components of the 
multifactorial intervention, including physical exercise;23 (3) patients with cognitive impairment are more 
susceptible to the adverse consequences of fall injuries;8 and (4) the inclusion of patients with cognitive 
impairment will enhance the generalizability of this pragmatic trial, facilitate the subsequent translation of 
results into clinical practice, and reduce the likelihood of selection effects. Patients with significant cognitive 
impairment/dementia will be required to have a caregiver/proxy willing to: (1) provide consent; (2) facilitate 
adherence to the study protocol, and (3) assist with implementing the intervention as needed.   
Significant cognitive impairment will be defined as 4 or more errors on the Callahan 6-item cognitive screener.  
The six-item screener is a brief and reliable instrument for identifying participants with cognitive impairment 
and its diagnostic properties are comparable to those of the full Folstein Mini-Mental State Examination 
(MMSE). The six-item screener can be administered by telephone and is easily scored by a simple summation 
of errors. The six items include the three-item recall (apple, table, penny) and three-item temporal orientation 
(day of the week, month, year) from the MMSE.  Additional information about the inclusion of patients with 
cognitive impairment is provided in the Informed Consent section. 
4.3.4 Rescreening 
Patients who screened out initially as low risk for the centralized strategy will not be rescreened.  Because 
screening will be imbedded in the usual work flow for the clinic strategy, patients who screened out initially as 
low risk will be rescreened during subsequent clinic visits. However, screen positive patients who had 
previously opted out or declined to participate will not be re-contacted, even if they screen positive during a 
subsequent clinic visit. 
4.3.5 Early Withdrawal of Participants 
Because this trial is based on the principle of “intent-to-treat”, all participants in a particular practice will be 
analyzed in the group to which that practice was randomly assigned, regardless of whether they complete the 
intervention or are noncompliant.  This preserves the effect of randomization.  Because the intervention will be 
integrated into the work flow of the practice, we expect withdrawals from the intervention will be limited. 
Nonetheless, we plan to follow participants for the study outcomes even if they elect to stop the study 
intervention. For participants who are lost to follow-up, we will be able to obtain some information from the 
electronic health record or from the utilization or claims data on the primary outcome of serious fall injuries.   
If the participant elects full withdrawal from the study, this will be recorded on the Participant Final Disposition 
Form and all contact with the participant will cease, as will any acquisition of participant data (e.g., CMS 
claims, clinical trial site encounter data, or medical records). 
5. STUDY INTERVENTION 
The intervention focuses on quality improvement and includes a multifactorial risk assessment and 
individually tailored set of recommendations/interventions.  The intervention will utilize a primary care co-
management model with nurse Falls Care Managers (FCM) that follows four steps: 
 
Risk assessment by a FCM using a standardized structured visit note. 
 
Use of structured visit notes and algorithms to develop an individualized Falls Care Plan by the FCM 
that will be presented to the patient’s primary care physician (PCP) for modification and approval, to 
include:   

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16
o Fall risk reduction interventions that the FCM can directly implement; 
o Recommendations that the PCP can implement (e.g., medication changes); 
o Referrals to health providers or community-based organizations for more detailed assessment 
or implementation of specific components identified in the Risk Assessment. 
 
Explanation of identified risks to the patient (and caregiver, when appropriate) and suggested 
interventions, using motivational interviewing to elicit patient preferences and readiness to participate in 
treatments.  
 
Ongoing monitoring of response to treatment as indicated in the Care Plan and reassessment of risk 
factors at scheduled intervals by the FCM with revision of the Care Plan as needed. 
The broad pillars of the intervention (e.g., the FCM), the linkage with health care system providers, and 
referrals to community-based programs) are consistent across practices.  Moreover, the content of the 
individual components is consistent across sites. As with all quality improvement efforts, implementation 
depends upon local resources; accordingly, the precise approach to implementation will vary from site to site 
and sometimes from practice to practice.   
Below are the specific activities to be implemented for each patient. The detailed information and procedures 
relating to Intervention fidelity and quality assurance are contained in the Manual of Procedures. 
5.1 Activities Prior to Initial Visit 
a. Identification of Participants. Eligible participants (i.e., those who have met eligibility criteria and 
consented to the study) are identified by the RAC and their names are transmitted to sites as well as 
information regarding cognition to determine whether the patient or caregiver is the informant for the 
pre-visit call, initial visit, and subsequent communication.  For patients with significant cognitive 
impairment/dementia, defined as 4 or more errors on the Callahan 6-item cognitive screener, the 
caregiver/proxy will be interviewed for the pre-visit call and will need to accompany the patient to the 
initial visit to provide clinical information.  
  
b. Scheduling and sending pre-visit forms to patients.  
 
c. Pre-visit calls. FCMs will conduct the pre-visit phone call and obtain additional information. 
5.2 Activities During and Immediately After Initial Visit 
a. Initial visit.  
i. Determining individual risk factors based on findings from Pre-Visit Questionnaire (PVQ) 
and initial assessment. All risk factors will be assessed through PVQ review and physical 
examination. Some specific risk factor protocols will be applied to all participants whereas others 
will be applied only to patients who meet specified criteria (triggers). 
 
ii. Linking risk factors to possible interventions. For each risk factor, standard of care interventions 
will be identified and a template will be used to communicate the recommendation; the template will 
include several different messages depending upon what the risk factor-specific protocol 
determines is appropriate for the patient. Risk factors and triggers include: 
1. Medications.  
a. Triggers. Fall Risk Increasing Drugs (FRIDs) or symptoms identified from PVQ. 
2. Osteoporosis.  
a. Triggers. All patients. 
3. Vitamin D.  

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17
a. Triggers. Only patients who have had a vitamin D level drawn within the last year. (Vitamin 
D recommendations for all others will be covered in Osteoporosis). 
4. Home safety.  
a. Triggers. All patients complete a home safety checklist prior to initial visit that is reviewed 
with the FCM. 
5. Orthostatic hypotension.  
a. Triggers. Patients identified with orthostatic hypotension during initial visit. 
6. Visual impairment.  
a. Triggers. Patients who have not been seen by eye doctor in past year or have vision risk 
factors (macular degeneration, glaucoma, diabetic eye disease, near or far vision loss) even 
if they have seen an eye doctor within the past year. 
7. Unsafe feet and footwear.  
a. Triggers. All patients. 
8. Strength, balance, gait impairment.  
a. Triggers. All patients. 
iii. Patient engagement/motivational interviewing. Patients identify 1-3 recommendations to initially 
work on and develop action items with FCM. 
iv. Care Plans will be developed based on action items. 
v. Approval of Care Plans by Primary Care Provider (PCP). 
b. Follow up with FCM. For each participant, the frequency and timing of follow-up visits to reassess risk 
factors and monitor progress towards risk factor reduction will be determined by the patient’s individual 
needs as defined in the Care Plan and initial visit EHR note. During the time when components of the 
intervention are being implemented actively, many participants will need to see or communicate with 
the FCM frequently to monitor progress and change the treatment plan and implement alternative 
interventions if there is failure to improve. 
c. Documentation of care will be site specific and will include: 
i. Initial visit and referrals. 
ii. Follow-up (in-person, telephone, e-mail) contacts.  
iii. Storage of clinical documents (e.g., PVQ, home safety checklist). 
5.3 Activities After Initial Visit and Between Visits 
a. Referrals to other health providers will be based on the individual patient’s specific risk factors 
and chosen action items.  Referrals include resources: 
i. Within health system.  
ii. Home health.  
iii. Community-based falls prevention programs. 
b. Acute and recent falls will be managed by the practice and FCM according to standards of care. 
c. Follow-up visits. 
i. Routine. During the first year of the intervention, all participants will be seen by the FCM at least 
twice and after the first year at least annually to mitigate new risk factors, consistent with AGS/BGS 
guidelines. During scheduled follow-up visits, the FCM will re-assess risk factors and repeat 
physical performance (SPPB) assessments. 
ii. Triggers for additional follow-up visits. Because acute illness can precipitate deconditioning and 
place participants at higher risk of falling, all participants will be scheduled to see the FCM for a 
reassessment following discharge from the hospitalization or after an Emergency Department visit. 

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18
6. CONTROL INTERVENTION 
6.1 Activities after Screening 
Eligible patients (i.e., those who have met eligibility criteria and consented to the study) are identified by the 
RAC (see 4.3.2), and their names are transmitted to the relevant clinical sites. 
6.2 Activities Conducted at the Sites 
a. Providers in the control group practices, i.e. usual care, will receive the results from the screening 
questions to identify age-eligible patients at high risk for falls.  
b. Patients receiving care at Control group practices will receive a falls informational booklet and will be 
encouraged to discuss fall prevention with their primary provider at their next clinic visit. This booklet, 
entitled “Stay Independent”, is part of the STEADI tool kit.   
c. A webinar about falls and fall prevention will be available to providers and staff in the control practices. This 
will be based on the existing fall prevention webinar, which is part of the STEADI tool kit. 
6.2.1 Rationale 
All patients enrolling in STRIDE will be told that their practices are delivering fall prevention programs. The 
control group needs to receive some fall prevention information that is part of the current standard of care for 
the following reasons:  (1) all participants will be at increased risk for falls, so there is an ethical obligation to 
inform their PCP;  (2) to increase adherence to using the fall calendars (and avoid differential reporting of the 
study’s primary outcome between the two groups), the control group needs to believe that they are part of 
some program to prevent falls;  (3) to avoid cross-overs to the intervention group (i.e. patients choosing to 
change their practice if they believe other patients in their health system are receiving superior care at 
practices located near their home) or drop-outs from the study (i.e. patients refusing to report falls and/or to 
allow their health information to be shared), it is important that the control group does not perceive that they 
are receiving a clearly inferior intervention.   
STRIDE will provide the control participants with materials that are part of the STEADI tool kit.  These materials 
have been produced by the CDC to raise awareness about falls in primary care.  These materials can be 
considered part of standard of care since they are currently being disseminated widely in primary care 
practices around the country. 
7. OUTCOME MEASURES 
7.1 Definition and Ascertainment of Outcomes 
Our approach to choosing outcome measures and assessment methods has been informed by discussion with 
our patients and stakeholders. With their help, we reviewed measurement domains from the Prevention of 
Falls Network Europe (ProFaNE) consensus.24 Based on these discussions and review of the literature, we will 
assess outcomes in two domains: 1) fall-related and 2) well-being, as summarized in Table 2. 
 
 

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19
 
7.1.1 Fall-Related Outcomes 
The primary outcome of serious fall injuries is defined as: a fall resulting in: (1) (fracture other than 
thoracic/lumbar vertebral; joint dislocation; or cut requiring closure) AND any medical attention; OR (2) (head 
injury; sprain or strain; bruising or swelling; or other) requiring hospitalization. 
A fall is defined as “an unexpected event in which the participant comes to rest on the ground, floor, or lower 
level.”24  To ensure that this definition is met, participants are asked, “Did you fall all the way fall to the floor, 
ground or other lower level when you fell?”  
All fall injuries, a secondary outcome, include serious fall injuries as well as less severe falls that result in 
bruises, cuts, persistent pain, and restricted activities, but not necessarily medical attention. The importance of 
these less severe injuries was recognized and articulated by our stakeholders. We propose to collect data on 
falls, serious fall injuries (both as defined by the current primary outcome and as defined by the original 
definition of the primary outcome) and other fall injuries every four months in all participants using a structured 
telephone interview. This interview will ask about falls, injuries, hospitalizations, emergency department (ED) 
visits, and other health care utilization.  To facilitate recall, participants will be instructed to record their 
falls/injuries on a monthly fall calendar.25,26 To enhance efficiency and consistency, ascertainment of these 
outcomes will be conducted centrally at Yale, which has an unparalleled track record for falls surveillance and 
participant retention.  
To confirm participant reports of the primary outcome (serious fall injuries) and identify instances of the primary 
outcome that were not reported by participants, we have developed a verification system based on 
administrative health care claims and encounter data that will be provided by sites and by Medicare, and 
medical records that will be provided by sites.  Participants reporting a fall-related injury that led to medical 
attention will have this injury confirmed in administrative claims/encounter data; we will request medical 
records when administrative claims/encounter data do not confirm the injury.  Once appropriate data have 
been assembled as noted above, fall-related injuries will be reviewed independently by two members of the 
Table 2. Primary and Secondary Outcome Measures, assessed centrally by Yale RAC 
Domain 
Measure (1˚ & 2˚) 
Source, Frequency, and Sample 
Fall-
related 
Serious fall injuries (1˚) 
 
Telephone interview every 4 months, supplemented by administrative 
claims/encounter data (including data from clinical trial sites and Medicare) 
for date and type of injury; medical record adjudication for discrepancies with 
fall-injury claims 
All fall injuries (2˚) 
Telephone interview every 4 months: serious fall injuries plus other injuries 
that may not come to medical attention 
Original operationalized 
definition of primary 
outcome (2˚) 
Telephone interview every 4 months, supplemented by administrative 
claims/encounter data (including data from clinical trial sites and Medicare) 
for date and type of injury  
All falls (2˚) 
Telephone interview every 4 months  
Well-
being 
  
Concern about falling (2˚) 
Modified FES at baseline, 12 m and 24 m (telephone) in 720 participants, 
representing a random sample of participants enrolled in first 12 months 
Physical function and 
Disability (2˚) 
LL-FDI via CAT at baseline, 12 m and 24 m (telephone) in 720 participants 
Anxiety/Depressive 
symptoms (2˚) 
PROMIS scales measured at baseline, 12 m and 24 m (telephone) in 720 
participants 
CAT: Computer Adaptive Testing; FES: Fall Efficacy Scale; LL-FDI: Late-Life Function and Disability Instrument; 
PROMIS: Patient Reported Outcomes Measurement Information System 

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20
Outcomes Adjudication Committee (OAC), which will be masked to group assignment.  These physicians will 
use available data to confirm: a) the occurrence of a fall; b) whether a fall-related injury has occurred; and c) 
the type of injury.   For cases where the two initial reviewers disagree and cannot reconcile their differences, 
the OAC as a whole will review the case masked to group assignment to make a final designation.  Similar 
procedures have been used successfully in the Lifestyle Interventions and Independence for Elders (LIFE) 
Study, under the direction of Dr. Gill.27  This triangulation approach will ensure that the primary outcome is 
captured accurately and completely. 
Process for Linking to Data from Medicare:  The Medicare ID/SSN are needed as the link to the patient’s 
Medicare data.  Subjects provided consent for us to review their medical records at the time of enlistment into 
STRIDE.  The 10 Clinical Trial Sites (CTSs) will be instructed to supply enrolled participants’ Medicare ID, SSN 
or both if they have both along with the STRIDE ID directly to a third-party vendor. To prevent a mismatch, the 
CTS will send two additional identifiers, date of birth and gender, which the third-party vendor can compare 
against lists provided by the Yale DCC (i.e., STRIDE ID, date of birth, gender) to make sure there is no 
mismatch between the STRIDE ID and Medicare ID/SSN.  
The SSN/Medicare ID will have two legs to its journey. The first leg is from the STRIDE CTS to Health 
Information Solutions. The second leg is from Health Information Solutions to General Dynamics Information 
Technology (GDIT). GDIT, acting as a contractor for the Centers for Medicare and Medicaid Services, will then 
use the Medicare ID and/or SSN to identify patients’ Medicare enrollment and claims data that is needed, after 
which GDIT will strip out the Medicare ID/SSN so the central STRIDE team researchers never see it. Because 
the Medicare ID/SSN are sent to GDIT with the STRIDE ID next to each Medicare ID/SSN, when the Medicare 
ID/SSN are stripped out, we still have the STRIDE ID left, which we can use to identify our patients. 
Health Information Solutions is acting as a third-party intermediary to save STRIDE researchers from 
responsibility to manage the SSN’s/Medicare ID’s themselves. GDIT is the CMS’ contractor that handles CMS 
data for researchers. It should be noted that while ResDAC and GDIT are acting on behalf of CMS, Health 
Information Solutions is acting on behalf of STRIDE.  Since Health Information Solutions is providing a 
technical service to STRIDE, they are being treated as a vendor by Yale and are considered covered under the 
entity to whom they are providing the service (in this case, Yale).   
The Centers for Medicare and Medicaid Services Privacy Board approved the use of their data to be able to 
complete this linkage process. 
7.1.2 Well-Being Outcomes (assessed by phone at baseline, 12m, and 24m in random sample of 720 
participants enrolled in first 12 months) 
Based on input from stakeholders, the four indicators of well-being will include: fall efficacy, physical 
function/disability, anxiety, and depressive symptoms.  We identified instruments that were brief and could be 
administered by phone.  We gave preference to computerized adaptive testing (CAT), when available, and to 
demonstrated responsiveness to change in studies of comparable populations.  Fall efficacy will be 
operationalized as the level of concern for falling (4-point scale: not at all, somewhat, fairly, very) when 
performing a series of activities, using a modified version of the Fall Efficacy Scale (FES).28 While fall efficacy 
had been operationalized originally as degree of confidence,29 more recent work by the ProFaNE group has 
asked about level of concern.  Fall efficacy has been used previously as an outcome in two successful 
interventions to reduce falls30 and improve falls care in primary care.17  
The Late-Life Function and Disability Instrument (LL-FDI) measures two areas that stakeholders viewed as 
important consequences of sustaining a fall injury (physical function and disability).  The LL-FDI has been 
validated psychometrically31 and can be administered efficiently by phone via CAT.32  The physical function 
area includes items such as going up a flight of steps, getting in/out of a car, and walking around one’s home; 
while the disability area includes items such as visiting friends/family, taking part in organized social activities, 
taking care of personal errands and preparing meals.  The LL-FDI is responsive to interventions designed to 
improve physical function, and effect sizes of .3-.45 SD units are considered minimally important differences.33 

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We will use the Patient Reported Outcomes Measurement Information System (PROMIS) to assess anxiety 
and depressive symptoms.34 The eight-item anxiety short scale asks about the frequency of feeling fearful, 
worried or anxious (among others), while the eight-item depression short scale asks about the frequency of 
feeling worthless, hopeless or having nothing to look forward to (among others).  Somatic items are not 
included because they are confounded with symptoms of frailty, do not fit the item response theory model well, 
and exhibit differential item functioning by age.34 The brevity of these measures obviated the use of CAT.  
These measures are responsive to clinically meaningful changes over time,35 using both mixed methods and 
anchor-based effects. Changes of 0.33 to .5 SD units have been observed36 in very similar PROMIS cancer 
instruments, and an effect size of 0.33 is considered a minimally important difference.37 
 
7.1.3 Tertiary Outcomes 
Tertiary outcomes will include hospitalizations (from interviews and claims), long-term nursing home 
admissions14 (from interviews and claims), and deaths.  
  
8. STUDY PROCEDURES AND VISITS 
 
8.1  Randomization 
The trial has a cluster randomized design. The unit of randomization is the practice. This avoids the potential 
for contamination of controls, allows staff to be trained efficiently, and improves the feasibility of applying the 
intervention practice-wide.  

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8.2 Schedule of Events 
The trial Schedule of Events is shown in Table 3. 
The STRIDE Study will follow subjects for up to 44 months through contacts every four months to 
inquire about falls. At 12 and 24 months, selected participants will have a longer contact for the 
Wellbeing outcomes subsample (n=720). 
 
Activity/assessment 
 
Screen
/ 
Enroll 
 
BL 
4 
mon 
8  
mon 
12 
 mon 
16  
 mon 
20   
mon 
24 
 mon 
28  
 mon 
32  
 mon 
36   
mon 
 
40   
mon 
 
44   
mon 
Screening for high fall risk 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Recruitment packet mailed 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment - Verbal Consent / Assent 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Telephone interview 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Demographic characteristics 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Cognitive screen 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Chronic conditions 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Fall history 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Self-rated health, height/weight 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical function and disability* 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
Concern about falling* 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
Anxiety/depressive symptoms* 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
Falls, fall injuries, serious fall injuries 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Health care utilization 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BL: Baseline; mon: months 
*Among a random subset of 720 participants 
 

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23
 
9. STATISTICAL ANALYSIS, SAMPLE SIZE AND POWER CALCULATIONS 
9.1 Design Overview 
STRIDE is designed as a cluster randomized, parallel group superiority trial with practices stratified by 
healthcare system and patients nested within practices. The unit of randomization is the practice to avoid the 
potential for contamination of controls, which could occur more easily if randomization was at the level of the 
participant or physician. The primary outcome is time to first adjudicated serious fall injury assessed at the 
patient level. The target sample size is 5,322 participants enrolled in 86 practices to provide 90% power to 
detect a 20% reduction in the rate of the primary outcome with intervention relative to control.  
Adaptive design features will include: 1) monitoring the accrual rate to determine whether the eligibility criteria 
need to be reconsidered if recruitment is lower than expected, e.g. by lowering the age entry criterion; 2) 
monitoring the potential for ascertainment bias because of interactions between the FCMs and study 
participants and changing the primary outcome definition if necessary; 3) monitoring the primary outcome rate 
to determine whether the outcome needs to be adapted, e.g., from first serious fall injury to all serious fall 
injuries if the former rate is too low, affecting the power of the study; 4) interim monitoring for efficacy or futility; 
and 5) refining the analytic methods based on the validity of the assumptions; such an adaptation will be done 
blinded to treatment, e.g., if the death rate is low, competing risks could be considered as a secondary, rather 
than a primary analysis.  Because the recruitment period will be relatively short, other commonly used adaptive 
features were deemed to be infeasible, such as adapting the randomization, intervention or sample size (based 
on nuisance parameters, e.g., intracluster correlation [ICC]) and/or observed treatment effect).38  
9.2  Subject Allocation to Treatment Arms  
All participating clinical practices will be randomized at one time using a stratified randomization approach with 
stratification by clinical site to control for potential site differences. Practices will not be added after trial 
initiation. The method of randomization will balance practice characteristics within and across the clinical sites 
to enhance homogeneity and to provide some control for the ICC to maintain the power of the trial. The 
balancing covariates include practice size, geography (urban/rural), and race/ethnicity.  
An important consideration, particularly in cluster trials, is allocation concealment to control for selection bias. 
Potential approaches include 1) randomizing after enrollment, 2) blinding the recruiters, 3) standardizing the 
enrollment process with adequate training of screeners and recruiters, and 4) covariate adjustment in the 
analysis. Because enrollment must occur after practices have been randomized in STRIDE, the first approach 
is not feasible. However, as discussed under Recruitment, we will mitigate the possible effects of selection bias 
through approaches 2 and 3, along with covariate adjustment in the analysis, if necessary.  
9.3 Sample Size  
Sample Size estimates were informed by preliminary data from MOBILIZE Boston, a longitudinal study of 765 
community-living seniors, with monthly ascertainment of serious fall injuries.39 Although based solely on self-
report, the operational definition of serious fall injury was otherwise the same as in the proposed trial. Analyses 
were restricted to 135 participants meeting our entry criteria, with a median follow-up of 2.8 y. The annual rate 
of first serious fall injury was 18% (95%CI: 14%-24%); a preliminary estimate of the overall serious fall injury 
rate (including recurrent events) was comparable, at 21% (95%CI: 16%-24%).  For the proposed trial, we 
project an annual outcome rate in the control group of 14% to 18%, since fall injuries will be assessed every 
four months rather than monthly, and our protocol requires that serious fall injuries be confirmed by data from 
claims or medical records.  We project a 20% reduction in serious fall injuries (intervention relative to control, 
assuming constant and proportional hazards).  This reduction, which would have considerable clinical and 
public health impact, is intermediate between that found in Yale FICSIT (31% reduction in all falls) and 
Connecticut Collaborative  Falls Program (CCFP) (9% reduction in serious fall injuries), two prior multifactorial 

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24
fall prevention studies.30,40 Because many aspects of our intervention will be implemented at the level of the 
patient (as in FICSIT) rather than geographic region (as in CCFP), our effect size should be closer to that of 
FICSIT than CCFP, making the sample size estimates given here conservative.  
Sample size estimates were determined for a clustered design for time to first serious fall injury (the primary 
outcome) based on the logrank statistic in the presence of competing risk due to death.41-43  Table 4 provides 
sample size estimates for a trial duration of 3 y assuming: 1) type I error = 5% (2-sided) and 90% power; 2) 
uniform accrual with periods of 1, 1.5 and 2 y; 3) equal allocation to intervention and control groups; 4) no 
adjustment for non-adherence to intervention (accounted for with conservative treatment effect); 5) all patients 
followed to end of the trial (max = 3 y); 6) 7% annual death rate without experiencing a serious fall injury (i.e., 
competing risk); 7) 3% annual loss to follow-up in the absence of serious fall injury or death (expected to be 
low due to the use of multiple sources, including claims data, but will be examined in Year 1 due to potential 
impact of migration out of the healthcare system; 8) 3% inflation for the proposed interim monitoring for efficacy 
and futility;44 and 9) 57% inflation for the design effect (DE) of clustering, assuming an average of 75 
participants enrolled per practice and an ICC of 0.0076 estimated from an analysis of serious fall injuries in the 
LIFE Study.45 Based on Table 4, we had selected a target sample size of 6000 participants to be accrued from 
80+ practices, each enrolling an average of 75 participants over a 1.5 year recruitment period. The target 
number of serious fall injuries to detect a 20% reduction for intervention relative to control at 90% power is 845 
(unadjusted for clustering or interim monitoring). When the duration of the study was extended to 40 months, 
sample size was revised to 5,322 participants.   
Data from the pilot study indicate that recruiting the desired number of participants is feasible. First, to achieve 
the targeted sample size, we will need to enroll about 4 participants per month per practice. During the pilot 
study, 164 participants who met the inclusion/exclusion criteria described in Table 1 were enrolled from 10 
practices (1 from each clinical site) over an average of about 1 month, a rate of about 16 participants per 
month per practice. The target rate was exceeded by all practices. Second, central screening will be the 
primary method of enrolling age-eligible participants. The probability of being enrolled using central screening 
was 0.08 in the pilot, which included a 50% nonresponse rate.  To increase the response rate, we will send out 
a second mailing to nonresponders.  A 
few sites will use a clinic screening 
strategy that had a probability of 
enrollment of 0.16 in the pilot. 
Therefore, we conservatively estimate 
that about 10% of screened patients will 
be enrolled in the trial. Thus, to enroll 
6000 participants, we initially estimated 
a pool of 60,000 age-eligible patients 
would be required.  
 
 
 
9.4 Sample size and power for secondary outcomes 
Power for all fall injuries and all falls (regardless of injury) was calculated using the same assumptions as 
above, but with a 1% Type I error to control for multiplicity and no adjustment for interim analysis. Annual rates 
of first fall and first fall injury from MOBILIZE Boston are 0.92 (95%CI: 0.75, 1.10) and 0.57 (95%CI: 0.46, 
0.69), respectively. Using conservative rates of 0.70 and 0.40, and based on the targeted sample size of 6000, 
power is > 99% to detect a 20% reduction with intervention relative to control for both of these secondary 
outcomes. For the indicators of well-being, an unadjusted sample size of 524 participants is required to detect 
Table 4. Sample size estimates. 
Accrual Period 
(Years) 
Annual Event Rate, 
Control Group 
Total Sample 
Size 
1 
0.14 
5680 
0.16 
5036 
0.18 
4535 
1.5 
0.14 
6190 
0.16 
5474 
0.18 
4920 
2 
0.14 
6844 
0.16 
6046 
0.18 
5426 
0.18 
5426 

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25
a standardized effect size of 0.3 between intervention and control at 1 and 2 years with 80% power and 1% 
type I error. The sample size adjusted for missing outcomes due to death (10%/y) and lost to follow-up (5%/y 
with or without a serious fall injury), and for clustering (DE = 6% assuming ICC = 0.0076 with 80 practices each 
enrolling 9 participants) is 720 (360 per group), a 12% subsample of the 6000 participants.  
9.5  Interim Monitoring   
Interim monitoring will focus on patient accrual, baseline comparability of treatment groups, protocol 
adherence, loss to follow-up, data completeness and quality, accrual of fall events, safety, efficacy, and futility. 
A risk-based monitoring approach15 will be taken focusing on centralized monitoring that will include: 1) 
monitoring data quality in real time (e.g. values out of range, missing data); 2) conducting statistical analyses to 
identify trends in the data; and 3) developing metrics for monitoring practice performance (e.g., practice report 
cards) based on the aggregated data, such as enrollment of ineligible patients, protocol violations, timeliness 
and quality of the data, losses and withdrawals. The inter-practice variation will be measured by the intracluster 
correlation coefficient (ICC) calculated for the primary outcome, serious fall injuries. Because the ICC has a 
direct impact on the power of the trial, it will be carefully monitored by the DCC and reported to the DSMB in 
closed session to ensure that power is adequate, recognizing that early estimates based on limited data may be 
unstable. A set of data monitoring tables will be developed as part of the Statistical Analysis Plan (SAP) that 
includes the above elements for presentation to a Data Safety Monitoring Board (DSMB) at approximately 6-
month intervals.  Per RFA, a “preliminary statistical analysis of the effects of the preventive strategy on the rate 
of serious fall injuries must be reported in March 2017.”  At this time, recruitment will have ended and about 
55% of the expected number of primary events will have been accrued, sufficient for an interim look.46 (The 
expected number of events is based on the ratio of average follow-up time at the interim look [1.25 y] relative 
to the average total follow-up time for the study [2.25 y, assuming recruitment begins on June 1, 2015].)  Thus, 
we propose consideration of stopping the trial at this time only for compelling evidence of efficacy (~p<0.008) 
or a trend in the wrong direction (i.e., futility) taking into account trends in secondary outcomes.  Future looks 
will be left to the purview of the DSMB based on emerging trends in the data; however, by March 2017, there 
will be less than one year left in the trial and it may be impractical to conduct another interim look before it ends 
in February 2018.  Interim monitoring boundaries will be established using an alpha spending approach.44,46 
The original proposal to the DSMB included an interim look in March 2017, but that date was considered 
unrealistic because of the trial’s late start and the accrual of insufficient numbers of adjudicated events by that 
date. Accordingly, the sponsors and the DSMB left the exact timing and content of the interim monitoring to the 
discretion of the investigators. At its May 31, 2017 meeting, the trial’s DSMB approved a revision to the interim 
monitoring plan specifying “that a formal interim analysis for efficacy or futility with the potential for early 
termination may not be necessary, and that a final decision about a formal interim analysis can be made 
sometime in 2018.” 
9.6  Statistical Analysis Plan 
This section provides an overview of the analytic plan for the final analysis, which consists of comparability of 
treatment groups, safety, and treatment efficacy. Per protocol, the analytic plan will be refined based on the 
validity of the assumptions; such an adaptation will be done blinded to treatment, e.g., if the death rate is low, 
competing risks could be considered as a secondary, rather than a primary, analysis. The analysis of the 
primary and secondary outcomes will be according to the principle of intent-to-treat (i.e., practices/participants 
will be analyzed according to their original treatment assignment regardless of adherence to protocol). All 
analyses will account for the cluster design with the participant as the unit of analysis. SAS 9.4 and R 3.6.1 
software will be used for all analyses. Comparability of treatment groups will be assessed by comparing the 
distribution of baseline characteristics in the two groups using appropriate graphical procedures, summary 
statistics and multivariate methods. The randomization is designed to produce balance on important covariates 
at the practice level (unit of randomization) but not necessarily at the patient level. Therefore, in a secondary 
analysis, the following pre-specified set of baseline covariates will be selected for adjustment to determine their 
influence on the treatment comparisons: age, sex, race/ethnicity, education, number of chronic conditions, and 

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26
number of positive screening items (out of three) for serious fall injuries.47 Analysis of safety will involve 
tabulating the occurrence of serious adverse events (SAEs) between the two groups using methods 
appropriate for discrete and continuous measures.  SAEs will be tabulated both on a per event and per patient 
basis. Survival rates will be monitored and calculated by the method of Kaplan-Meier.         
Analysis of the primary outcome will be done using a survival model that incorporates competing risks (due 
to death) and clustering. 48,49 The model will be adjusted for the randomization of practices by healthcare 
system and include the covariates used for the constrained-covariate randomization (practice size, location 
and race/ethnicity). Participants lost to follow-up without a prior serious fall injury will be censored at their date 
last seen. In a sensitivity analysis, we will also adjust for the pre-specified set of baseline covariates to 
examine their influence on the treatment comparisons. Standard approaches (e.g., examination of Martingale 
residuals and the proportional hazards assumption) will be used to examine the fit of the models. The effect of 
intervention relative to control will be estimated as a hazard ratio with corresponding 95% confidence intervals. 
Also, in a supplementary analysis, we will obtain an estimate of the intervention effect at the practice level. The 
effect of intervention will be evaluated in the following five pre-specified subgroups of participants using 
appropriate tests of homogeneity (e.g., interaction): age (70-79, 80+), sex (male, female), fear of falling alone 
(yes, no), multimorbidity (0-1 chronic conditions, 2+ chronic conditions), and hip fracture or other fracture since 
age 50 (yes/no) adjustment for multiplicity will be done using the method of Hochberg.50 The cumulative 
incidence of serious fall injuries will be estimated using non-parametric maximum likelihood methods (Aalen-
Johansen estimator) 48 and will be used to estimate freedom from falling over the entire follow-up period. Also, 
in a supportive analysis, we will evaluate serious fall injuries as a recurrent outcome using a joint frailty model 
that accounts for clustering, competing risk and recurrent events. 51  An overall type-I error rate of 0.05 (2-
sided) will be used as the level of statistical significance for the primary endpoint. 
Analysis of the secondary and tertiary outcomes.  All fall injuries and all falls (regardless of injury) will be 
analyzed both as time to first event and as recurrent events similar to the primary outcome. Indicators of well-
being (fall efficacy, physical function, anxiety and depressive symptoms) will be analyzed using generalized 
linear mixed models assuming missing at random (MAR) with adjustment for baseline indicator of well-being 
and factors that are predictive of missingness. Sensitivity analyses will be conducted to investigate the MAR 
assumption, such as methods that model jointly the missingness and outcome distributions.52 To provide 
some control for multiplicity, we will test the secondary outcomes using a significance level of 1% (2-sided) and 
report 99% confidence limits. Hospitalizations will be analyzed using a Poisson regression model accounting 
for practice-level clustering with follow-up time as an offset. Time to first long-term nursing home admission will 
be analyzed using a multistate model accounting for clustering (as described for the primary outcome). Death 
will be analyzed using the marginal Cox model.49 No control for multiplicity will be done for analysis of tertiary 
outcomes.  
10. DATA MANAGEMENT 
Components required to screen and recruit participants, collect baseline assessments, and obtain outcome 
data are managed centrally by the Data Coordinating Center (DCC). Field operations, including interviewing 
and mailings, are carried out by Recruitment and Assessment Center (RAC) staff following workflows that are 
supported closely by DCC systems. 
The main components of DCC support are: 
 
An Electronic Data Capture (EDC) system and database (REDCap) to support RAC field operations; 
 
A “portal” website to disseminate STRIDE information to the public, provide access to STRIDE 
resources, and to support intra-project communications; 
 
A website tool to support clinic screening; 
 
A website tool to support adjudications; 
 
A software application to support Falls Care Managers (FCMs); 
 
An administrative tracking application to support RAC office activities; and 

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27
 
A data mart of de-identified data in SAS format, for use by DCC programmers for conduct-of-study 
monitoring and analyses. 
 
These components are described below, in the context of the support they provide. 
10.1 Field Operations Support 
Almost all STRIDE data collection and data entry is based on REDCap, an NIH-supported electronic data 
capture (EDC) application that is used at more than 1000 institutions in 60 countries (http://project-redcap.org). 
The DCC hosts Yale's implementation of REDCap and has the expertise to employ thoroughly its many 
features, and to extend REDCap's capabilities as required to meet special study needs. 
10.1.1 Screening  
Central Screening will be the primary strategy for recruitment.  To maintain flexibility, clinic-based screening 
will also be available on a limited basis.  Under Central Screening, age-eligible patient contact data are 
imported from EHR data warehouses at each site and stored in a patient information database. Patients are 
randomly selected for screening from this database. The clinic screening protocols require clinic staff to 
administer the fall risk screen. The recruitment materials may either be handed directly to the patient or mailed 
by the RAC. 
10.1.2 Baseline Interviews 
The recruitment, consent and enrollment or “baseline” interviews will be managed using REDCap with 
extensions designed by DCC to better support the interviewers’ workflow. The Administrative Tracking 
application will identify newly enrolled participants and will provide tools to manage the post-enrollment 
mailings. 
10.1.3 Outcome Surveillance 
The Administrative Tracking application will identify participants nearing the end of their 4-month surveillance 
cycles so that they can be called for telephone interviews,.These data will then be made available to the 
outcomes adjudication team via a secure web-based tool designed by DCC. 
10.2 Website Tools 
10.2.1 STRIDE Portal (stridestudy.org) 
An important website developed and maintained by DCC is stride-study.org, which serves two main functions. 
First, it includes a public section that is used for disseminating STRIDE information.  
The second main function is to support STRIDE project activities. This section requires login authentication, 
and provides role-specific pages (Site Coordinator, FCM, etc.), blogs, study resources (including the screening 
and adjudication-support tools), discussion forums and other features. 
10.2.2 Screening Support 
DCC has developed a secure website tool for use by site coordinators to help them manage clinic screens and 
to monitor patient study status. Through this website, a site coordinator can identify patients for screening, 
enter screening data, and enter or update patient contact information. Specialized views are provided, such as 
lists of screen-positive patients and enrolled patients. 
10.2.3 Adjudication Support 

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28
Another secure website tool will support adjudication activities. Features offered will include:  
 
Access to claims/encounter data acquired from site EHR data warehouses; 
 
A means to request medical records; 
 
A means to enter claims and encounter data if unavailable from EHR systems;  
 
Access to scanned medical record documents (a PDF browser); and 
 
An administrative module for assigning interviewers and tracking the status of each adjudication. 
10.2.4 Intervention Support 
An important component of the intervention is specialized software that supports the Fall Care Managers 
(FCMs). This software has two major components: an electronic data capture module that is designed and 
maintained by DCC, and a workflow support module that is designed and maintained by an external vendor 
(High5LA). 
10.3 Administrative Tracking Application 
The Administrative Tracking Application will track each patient’s progress through the study, and provide lists 
and alerts for patients requiring action by the RAC.  It will also provide support for RAC office procedures. 
These include initiating and tracking all mailings, preparing and emailing monthly site “report cards,” managing 
gift card acquisition, distribution and replenishment, and other functions that are identified during the STRIDE 
field operations phase.  Many of these functions are based on tools already developed by DCC for other 
national studies.  
10.4 The Data Mart 
To facilitate the production of conduct-of-study reports, error-check reports and interim analyses, a read-only 
SAS “data mart” is maintained and updated weekly. The data mart is a well-documented, read-only snapshot 
of administrative and research data, in a format readily accessible to data managers and statisticians. The data 
mart is the basis for all conduct-of-study reports, which will be generated by SAS programs and posted on the 
Study Website. Permanent copies of the data mart will be created for DSMB reports and interim analyses.  
10.5 Data Security 
All of the databases described in this section are maintained on very strongly firewalled servers managed 
jointly by Yale Information Technology Services (ITS) and DCC.  These servers are not accessible outside the 
Yale internal network, and access to the databases are further restricted to a carefully controlled set of 
authorized DCC and RAC users. Servers are physically secured in environmentally-controlled server facilities 
to which access is limited to ITS and DCC systems staff.  Implementation of the DCC and REDCap database 
and application server is monitored by the Yale Information Security Office, and are certified as following Yale 
and NIH HIPAA guidelines. 
10.6 Protection from Data Loss and Downtime 
Secure, encrypted daily backups of all databases and applications are maintained by the DCC. All servers are 
configured with RAID 10 drive arrays that will survive the simultaneous loss of two drives.  To protect against 
downtime, the REDCap and STRIDE application and database servers will be duplicated in virtualized 
environments in two separate data centers, with documented failover procedures that will minimize downtime 
caused by a critical component failure in the primary system. 

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29
11. SAFETY AND ADVERSE EVENTS  
11.1 Background 
This section describes the requirements and processes for reporting adverse events (AE), serious AE (SAE) 
and unanticipated problems to the Central IRB, National Institute on Aging (NIA), and DSMB. It incorporates 
guidelines provided by the Office of Human Research Protections (OHRP) of the Department of Health and 
Human Services (DHHS) and Food and Drug Administration (FDA) reporting requirements. NIH is obligated to 
ensure that researchers comply with their approved reporting procedures.  Clinical trial investigators funded by 
NIA are obligated under federal regulations to appropriately inform the Institute of adverse events and 
unanticipated problems, and NIA is required to ensure that the appropriate procedures are in place to support 
this reporting. 
11.2 Definitions 
Adverse Event: Because 45 CFR 46 does not provide a specific definition for an adverse event (AE), the 
definition of an AE will conform to the International Conference on Harmonization (ICH) Good Clinical Practice 
(GCP) Guidelines. The same definition is used by the U.S. Food and Drug Administration (FDA) except that 
“drug” is typically used instead of the term “intervention.” An AE is defined as any untoward medical 
occurrence in a patient or clinical investigation subject administered an intervention and which does not 
necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with 
the use of an investigational intervention, whether or not related to the intervention. 
Serious Adverse Event (SAE): Any AE that: 
 
Results in death; 
 
Is life threatening, or places the participant at immediate risk of death from the event as it occurred;  
 
Requires or prolongs hospitalization; 
 
Causes persistent or significant disability or incapacity; 
 
Results in congenital anomalies or birth defects; 
 
Is another condition, which the investigators judge to represent significant hazards. 
Unanticipated Problem: any incident, experience, or outcome that meets all of the following criteria: 
 
unexpected, in terms of nature, severity, or frequency, given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and informed 
consent document; and (b) the characteristics of the study population;  
 
related or possibly related to participation in the research; in this guidance document, 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;  
 
suggests that the research places participants or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
Adverse Event Reporting Period: The study period during which adverse events must be reported is 
normally defined as the period from the initiation of any study procedures to the end of the study treatment 
follow-up. 
Preexisting Condition: A preexisting condition is one that is present at the time of providing the consent for 
the study.  A preexisting condition is considered an adverse event if the frequency, intensity, or the character of 
the condition worsens during the study period. 
 

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30
11.3 Responsibilities 
Both the NIA and the investigators it funds have responsibilities with respect to safety reporting. 
NIA program staff members are responsible for providing: 
 
Assistance to extramural investigators in understanding and applying adverse event and serious 
adverse event guidelines and for ensuring compliance with OHRP guidance in all NIA-funded clinical 
research. 
 
Oversight of these guidelines, which includes periodic review and revision as relevant rules and 
regulations change. 
 
Assurance that the Data and Safety Monitoring Plan (DSMP) addresses reporting of adverse events, 
serious adverse events, and unanticipated problems. 
 
Verification that all corrective action plans have been adequately implemented.     
 
Assurance that the study has an independent safety monitoring body commensurate with study risk 
(Data and Safety Monitoring Board or Medical Safety Officer).    
 
Ongoing oversight of the safety reporting process to assure that potential safety issues are addressed.  
Investigators conducting clinical research are responsible for: 
 
Assurance that their procedures are conducted in compliance with these guidelines. 
 
Submission of IRB-approved protocol to the NIA program office.  A DSMP that is commensurate with 
the study risks and reflects these guidelines will also be submitted to the NIA program staff.  
 
DSMP describes the plans for adverse events, serious adverse events, and unanticipated problems 
commensurate with the nature and complexity of the study. 
- 
Recipients of Serious Adverse Event and Unanticipated Problem reports must include the IRBs, 
DSMB or Medical Safety Officer, and NIA. 
- 
Adherence to the DSMP with respect to timely submission of adverse events, serious adverse 
events, and unanticipated problems. 
11.4 Level of Monitoring in this Study  
General Description/Overview: This pragmatic trial differs from a typical randomized, controlled trial (RCT) in 
important ways. First, no experimental interventions are used. All interventions are standard of care and not 
research. Indeed, the consent form does not include language for consent to an intervention, only for collecting 
data. Thus, the definitions of research and therefore AE, SAE, Unanticipated Problems and Pre-existing 
conditions do not apply to the intervention. However, this appraisal does not preclude the need to monitor the 
study and its impact on participant safety. There are no study visits; the only data collection methodologies are 
interviews, EMR review, and examination of claims data. Therefore, our safety monitoring procedures focus on 
data collection via the methodologies available in the protocol design. Our plan is based upon the following 
principles:  
1) It is not feasible or necessary for participant safety to monitor AEs as the definitions above do not apply 
because the intervention is not research. 
2) Limited monitoring is justified for serious adverse events (SAEs) as many of these will not occur in our study 
population (e.g. congenital anomalies) AND this is not a trial that has implications for FDA approval. Thus, only 
Good Clinical Practice (GCP) need dictate the level of monitoring in accordance with Federal Registry Title 21.  
3) It is not necessary to assign monitored SAEs as “related” or “unrelated” to the study protocol because there 
is inherent bias in this assessment, attribution of “relatedness” would be a tremendous burden, and whether a 

RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
 
 
31
difference in SAE burden is considered “related” or not, a significant difference between groups would be 
treated with similar concern by the DSMB.  
4) Mechanisms for timely reporting after SAE ascertainment are important, but collective totals of monitored 
SAEs at assigned intervals will meet “timeliness” for the purposes of this study.  
5) The primary and secondary study outcomes will not require additional SAE reporting even though they are 
likely to meet the definition of an SAE.  
11.5 Ascertainment of AE, Unanticipated Problems (UP), and SAE 
11.5.1 Adverse events 
As noted in 11.4, AEs will not be collected in this trial since “any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the intervention” will be 
occurring in the course of routine care, not research. Limited SAEs will be collected and reported as outlined in 
11.5.3. 
11.5.2 Unanticipated Problems (UP) 
Investigator institutions must have written procedures for ensuring prompt reporting to the IRB and NIA, and 
others as appropriate, of any Unanticipated Problem involving risks to study participants or others (45 CFR 
46.103(b)(5)).  As shown in Table 6, if the site PI or study coordinator has an individual concern, they will be 
required to contact the Medical Safety Officer (MSO) within 48 hours of first knowledge of the event.  An UP 
form must be completed by the investigator and faxed to the MSO within 48 hours.  The investigator/ 
coordinator will keep a copy of this UP form on file at the study site.  The MSO will confirm that the UP is an 
anticipated event and, if confirmed, report the UP to the DSMB and NIA within 48 hours of its notification. An 
UP will result in corrective plans and measures to prevent reoccurrence.  An electronic record of such 
concerns and the action plan will be filed by the MSO with the DCC so that concerns can be tabulated and 
reported as outlined below. 
11.5.3 Ascertainment of SAEs and Deaths 
Given the principles in 11.4, our plan focuses on a limited set of SAEs for acquisition and monitoring with data 
derived from the interviews, EHR data downloads and claims data. Only hospitalizations and deaths will be 
collected, which will ensure the protection of participants from potential harm but remain feasible within the 
study design. The vast majority of SAE ascertainment will occur from telephone interviews every 4 months 
and/or in aggregate via biannual data downloads from the EHR and claims data as described below If the 
event occurred within the same health care system where the participant usually receives care, it also will be 
confirmed via EHR review by the MSO. The aggregate claims data will be collated separately (to avoid double 
Table 6. Methods to ascertain safety concerns and SAEs 
 Site PI or FCM has specific concern  contact MSO directly; 
 Hospitalizations: 
 Four-monthly telephone interview reported hospitalization –assessed as one of the following: 
 Intra-health system  confirmed by MSO via EHR data; 
 Extra-health system  not confirmed, but tallied for separate reporting; 
 EHR data – reported in aggregate; 
 Deaths: 
 Four-monthly telephone interview - non-response will result in telephone call from the RAC to the designated 
contact person to assess status; 
 EHR data; 
 Death certificates (if needed for confirmation). 

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32
counting of events).  Self-reported hospitalizations will be reviewed quarterly by the Medical Safety Officer 
(MSO), as described in the Safety Plan. 
Participants who die within the participating health care systems will be verified by EHR review by the MSO 
from routine data transfers utilized for outcomes monitoring. However, participants, who die during the interval 
between their visits, at home or outside the participating health care systems, may be missed in this process. 
Therefore, when a participant is lost to follow-up we will ask their designated contact person whether s/he has 
died. If a death cannot be confirmed through the EHR, we will ask the relevant clinical site to obtain a death 
certificate.  These procedures worked well in the recent multi-center NIA-sponsored LIFE Study.  The National 
Death Index cannot be used routinely because of substantial delays in recording deaths, but will be considered 
as a back-up option.  We will also consider querying the CMS Master Beneficiary Summary File if needed.  
As outlined in the safety plan below, SAEs will be reported to the DSMB, cIRB and local IRBs in accordance 
with the NIH and local regulations, and in conformity with the Data and Safety Monitoring Plan developed by 
the DSMB and approved by NIA and PCORI.  
11.6 Safety Personnel 
Medical Safety Officer (MSO): The MSO will coordinate reporting of the safety data. The MSO will monitor 
and evaluate all collected UPs and SAEs from all sites efficiently and effectively by regular review/monitoring of 
reports of monitored SAEs or UP reported directly by site PIs/personnel. The MSO will have a critical role, 
ensuring that all participants receive the highest quality care and that safety concerns are foremost in the 
conduct of this trial. The MSO may suggest measures to the PIs to improve monitoring or prevent risk to 
participants. Upon approval by the DSMB, these modifications may be submitted as protocol modifications to 
the cIRB with communication to the local IRBs. The MSO will review reports of UPs and SAEs (in total, but not 
segregated by treatment assignment) and submit these to the DSMB, NIA, cIRB and the DCC for distribution to 
Reporting of Unanticipated Problems and Serious Adverse Events. 
A summary report of the UP and SAE collected by all methods of ascertainment will be prepared by the MSO 
and DCC for submission to the DSMB, NIA and cIRB in accordance with the Safety Monitoring Plan. 
12. ETHICAL AND REGULATORY CONSIDERATIONS 
12.1 Good Clinical Practice Statement 
The trial will be conducted in accordance with the ethical principles that have their origin in the Declaration of 
Helsinki, and that are consistent with the ICH guidelines for Good Clinical Practice (GCP) and all federal as 
well as local regulatory requirements. 
12.2 Informed Consent 
The principles of informed consent are described in ICH guidelines for GCP (ICH E6[R1]). The ICH used by the 
investigators at the trial sites will be reviewed and approved by the Trial’s DSMB prior to submission to the 
site’s IRB and Informed Consent. 
As noted previously in the screening procedures outlined above, participants identified by age and screening 
eligibility will be contacted by phone if they do not otherwise opt out. Informed verbal consent will be obtained 
by trained study personnel with all potential participants receiving a general description of the study, including 
the baseline and surveillance evaluations, along with the study specific evaluations. Importantly, written 
consent was not considered necessary to implement specific components of the intervention that will vary by 
risk assessment in any given individual, since it is facilitating standard of care in a consistent fashion, not 
providing an experimental intervention. The cIRB agreed with this premise in the pilot phase of the study and is 
anticipated to do so for this phase. Further, given the cluster randomized design, extensive discussion of the 
intervention for a specific individual may bias substantially the sample from site to site. Of course, data 

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33
collection does require consent and thus will be the primary focus of the consenting process. Verbal consent 
should be adequate per the learned opinion of two IRB Chairs (at Yale and Wake Forest) and approval of the 
process by the cIRB (Brigham and Women’s) in the pilot phase. 
Decisional capacity and proxy consent:  It is likely that potential participants with impaired decisional 
competency will be identified for this study by the Callahan 6-item screener as described previously. It is 
recognized that such participants need to be identified – not to exclude them from participation, but to identify 
those who require added processes to participate in an ethical manner. Therefore, at the time any potential 
participant is approached, professional judgment will be used to determine the need for alternate consent with 
assent by the participant. Study personnel responsible for recruitment and consent will be highly trained and 
experienced in determining decisional capacity in senior populations. In addition, specific assessment of 
decisional capacity will be part of study training. For example, potential participants will be considered impaired 
with regard to decisional capacity, regardless of the score on the Callahan 6-item screener, if they: 1) have an 
inability to express or communicate a preference/choice; 2) cannot understand the consequences of a potential 
situation – e.g. cannot understand the implications of releasing their personal health information (PHI); 3) are 
unable to provide a logical rationale for participation/non-participation; 4) have a legal guardian or have been 
identified legally as incompetent to make decisions for themselves. If there is any uncertainty, study personnel 
will be instructed to obtain proxy consent.  
When proxy consent is deemed necessary, the proxy will be approached for consent. Potential participants 
deemed not to have decisional capacity will be informed that their proxy is going to be approached. If 
permission is granted by the proxy to enroll the participant, the potential participant will then be notified and 
asked to provide verbal assent, using the following items defined clearly to the potential participant: 
 
A simplified description of the purpose of the research study including risks/benefits; 
 
A description of the measures/outcomes to be collected and their method of collection; 
 
An explanation of the procedures involved and how long the study will last; 
 
An indication that the study is voluntary; 
 
A question/answer opportunity in which the potential participant will be encouraged to ask questions. 
If verbal assent is granted, the participant will be enrolled. 
12.3 Institutional Review Board 
A central IRB (cIRB; Brigham and Women’s) will be responsible for review and approval of the protocol, any 
amendments, the informed consent form (ICF) and any other materials provided to participants. Delegation 
agreements to the cIRB have been signed for all clinical study sites; however, at each trial site, an 
appropriately constituted IRB as described in ICH guidelines for GCP will also be responsible for needed 
review and approval of the study protocol, ICF and any other materials provided to the participants within the 
terms of the delegation agreement. The site IRB will also review any amendment to the study protocol or ICF 

RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
 
 
34
unless the change is necessary to remove an immediate danger to the participant, in which case the IRB will 
be informed as soon as possible. 
The cIRB and site IRBs also will be informed of any event likely to affect the safety of the participant or the 
continued conduct of the trial. Records of IRB review and approval of study protocol, ICF, and amendments will 
be kept by the site PI.  
12.4 Protocol Amendments 
Any change in the study protocol must be approved by the DSMB, NIA, and the Project’s Steering Committee 
and approved by the cIRB and trial sites’ IRBs before it can be implemented. 
12.5 Risks to Human Subjects 
The risks associated with participation in the study intervention itself are deemed to be minimal because: 1) the 
intervention is aimed at maximizing participation in components of current standard of care; and 2) the 
intervention is being implemented by trained professionals in the care setting in which they typically provide 
care. Our assessment of minimal risk does not, however, preclude the possibility that adverse events, and 
serious adverse events could occur. Therefore, a comprehensive data safety monitoring plan is outlined in the 
following sections. Authority for monitoring the safety of the protocol will reside in an independent DSMB 
responsible for holding the PIs accountable for data quality and completeness, and assessing the ongoing 
safety of the trial participants through periodic meetings/review. Ongoing participant safety monitoring is the 
responsibility of site PIs who will report adverse events to a Medical Safety Monitor appointed by the PIs. The 
Medical Safety Monitor has the authority to directly report concerns to the DSMB if they arise. 
There are potential risks associated with data collection and information management and, in fact, these risks 
are the major reason consent will be required in this trial. These include inadvertent disclosure of personal 
health information or research data collected. Every effort will be made to inform the participant of this potential 
and minimize the risks as outlined below.  
12.5.1 Protection Against Risks 
Minimizing Risks: The study protocol will be implemented at each clinic only after the PI, Falls Care Manager 
(FCM), and study coordinator have undergone rigorous protocol training. The training and monitoring of 
performance in accordance with the Manual of Procedures for the study will be the responsibility of the study 
PIs (Drs. Bhasin, Gill and Reuben). All efforts will be made to minimize risks and participant inconvenience, 
and mitigate interruptions of therapy. Risks will be minimized by: 1) adequate training of all staff with 
proficiency testing; 2) ensuring participants are verbally informed of the details of the interventions as they are 
delivered; 3) frequently encouraging participant questions throughout the interventions; and 4) Serious Adverse 
Event (SAE) Reporting and monitoring overall study safety by a DSMB as outlined below. 
12.5.2 Potential Benefits of the Proposed Research to Human Participants and Others 
There are a number of potential benefits of the study for the participants including: 1) close monitoring of the 
participant during the trial; 2) identification of fall risk factors during the customized risk assessment; and 3) 
medication reconciliation by trained professionals with experience in the care of seniors. 
The potential societal benefits from this protocol are also substantial. Optimizing models of care for reducing 
the risk of serious fall injuries has the potential to greatly enhance patient care – including the potential to 

RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
 
 
35
reduce both morbidity and mortality, as well as reduce costs. Further, quality of life benefits may be derived 
from reducing injurious fall risk, particularly as one’s confidence in balance and mobility is increased.  
12.5.3 Importance of the Knowledge to be Gained 
The knowledge to be gained from this trial is substantial. Injuries that result from falls pose a substantial public 
health burden, especially among older persons with risk factors for falling. Serious injuries, including 
hematomas, broken bones and lacerations may be important factors that contribute to older persons’ loss of 
independence. This research proposal aims to mitigate this public health burden by rigorously evaluating 
whether the multifactorial intervention reduce the risk of serious fall injuries. Our major goal is to address the 
obstacles of effectively reducing falls risk including: 1) establishing an effective method for control over 
implementation of preventive interventions; 2) enhancing provider knowledge/expertise/adherence to 
guidelines; 3) overcoming geographic, racial, ethnic, and cultural barriers; 4) enhancing patient adoption of 
self-management risk modification; and 5) organizational structure and support needed to implement and 
coordinate multifactorial strategies. The sustainability and effectiveness of scalable, multifactorial strategies 
have not been assessed previously, but are goals of this clinical trial. 
12.6 Safety Monitoring Protocol 
Safety monitoring will be accomplished in accordance with Safety Monitoring Manual of Procedures (MOP) to 
be approved by the DSMB and NIA. NIA will endorse all members of the DSMB, and the DSMB will determine 
reporting procedures and meeting frequency outlined in the Safety Monitoring MOP. 
12.7 Inclusion of Women and Minorities 
As shown in Table 7, women are expected to constitute nearly 60% of the overall sample, consistent with the 
higher prevalence of falls among older women than among older men, and the higher life expectancy of 
women than men. Also, women are more likely to participate in clinical trials than men. Table 7 also 
summarizes the racial and ethnic background of the potential participants at each of the ten trial sites. In 
aggregate, based on the 2012 census data from the trial sites, 12.3% of potential participants >75 years of age 
at the trial sites are expected to be African-Americans, 11.0% Hispanics, and 4.3% Asian-Americans. These 
proportions are higher for each of these racial/ ethnic groups than those in the general US population.  
Table 7. Projected enrollment by sex, race and ethnicity  
Site 
Male 
Female 
Hispanic 
Black 
American 
Indian 
Asian 
Native 
Hawaiian/ 
Pacific 
Islanders 
White 
Essentia 
252 
348 
3 
3 
6 
3 
0 
588 
Health Care Partners 
300 
300 
360 
180 
4 
122 
24 
270 
Hopkins 
240 
360 
12 
150 
1 
18 
0 
431 
Iowa 
218 
327 
16 
16 
5 
5 
0 
518 
Mount Sinai 
200 
400 
149 
75 
9 
39 
0 
477 
Partners 
245 
355 
36 
60 
1 
24 
0 
515 
Pittsburgh 
222 
378 
12 
71 
0 
11 
0 
518 
Reliant 
245 
355 
41 
17 
1 
16 
0 
566 
UTMB 
240 
360 
6 
41 
2 
35 
2 
520 
Michigan 
226 
374 
66 
126 
2 
6 
0 
466 
Total 
2410 
3590 
703 
741 
32 
280 
26 
4921 
Percent 
40.2 
59.8 
11.7 
12.3 
0.5 
4.7 
0.4 
82.1 
Site-specific cell counts represent projected sex, race and ethnicity totals assuming 600 randomized patients at each of the ten 
trial sites, for a total of the original target of 6000 participants enrolled.  

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36
Some of the rural health care systems have a lower proportion of minorities than the US population by virtue of 
their location and demography. In contrast, other participating health care systems centers in urban areas, 
such as Johns Hopkins Health Care System in Baltimore, MD, and Health Care Partners in Los Angeles, CA 
have a substantially higher proportion of African-Americans and Hispanics in their patient population. Thus, 
60% of patients at Health Care Partners describe themselves as Hispanic, 24% of patients at the Mount Sinai 
Health Care System in New York, NY describe themselves as Hispanic, while 25% of patients attending the 
Johns Hopkins Health Care System describe themselves as African-American.  
We will utilize the help of our patient advisors and stakeholders to effectively recruit older men, and men and 
women in the minority communities.   
13. STUDY DOCUMENTS 
13.1 Retention of Records 
The site PI will retain all study-related documents for at least seven years following the completion or 
discontinuation of the study. If the site PI’s personal situation is such that such archiving can no longer be 
ensured, the PI will inform the Central Project Management and the relevant records will be transferred to a 
central secure location for storage. 
14. PUBLICATION AND DISSEMINATION POLICY 
The project PIs in discussion with the Steering Committee will establish a Publication and Dissemination 
Committee, which will set the rules for publication of the data and authorship in conformity with PCORI and 
NIH policies.  In accordance with PCORI’s legislative mandate on public dissemination, we will collaborate with 
NIH and PCORI in order to make the study’s findings available to clinicians, patients, and the general public 
not later than 90 days after the completion of the study. 
14.1 Dissemination 
The findings of this trial have important implications for public health and policy, requiring wide dissemination; 
additionally, several aspects of this trial’s approach and implementation will shape clinical practice and form 
the basis for dissemination after the trial. First, the screening methods will be built to interface with major EHR 
vendor software and will be readily transferable to any site using similar software. Second, instruments used 
for risk assessment and intervention management by the FCM can be used in any primary care practice. Third, 
patient materials will be adapted and used in the program and will be exportable after the trial. Fourth, training 
materials and procedures will be available for propagating “train the trainer” programs. 
A Publication and Dissemination Committee (PDC) will be established to oversee the dissemination of the 
study’s findings. The PDC will include members of the National Patients and Stakeholders Council (NPSC) and 
investigators with content expertise. This structure will allow the stakeholders and investigators to jointly 
address how to disseminate study findings to impact clinicians, patients, policy makers, communities, CMS and 
other third party payers. Also, local councils will work with investigators from the trial site to plan dissemination 
and implementation in local communities.  
Dissemination of study results will be accomplished through traditional routes (e.g. scientific meeting 
presentations, publications), but also through novel routes felt to be most effective by our patients and other 
stakeholder partners using the PCORI Dissemination and Implementation Action Plan begun through a recent 
roundtable. 
In the PCORI roundtable, the Agency for Healthcare Research & Quality (AHRQ) efforts in dissemination and 
implementation (D&I) were highlighted, with particular reference to AHRQ’s work with the Patient-Centered 
Outcomes Research Trust Fund (PCORTF) and its legislative role in assisting PCORI with D&I of research 
findings in this space. The framework for the PCORTF investments by AHRQ include prioritization and topic 

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37
development, message development and strategy selection, audience identification, training and career 
development, and infrastructure. Further, AHRQ has products and tools for D&I activities that could be utilized 
to disseminate widely the successful tools developed during this project. These tools include consumer and 
clinician summaries, decision aids, and publicly focused instruments such as public service announcements 
that can be leveraged to engage patients, consumers, and caregivers in shared decision making. Producing 
these materials is well beyond the budget of this project. However, since D&I is a key activity for PCORI after 
sponsored research is completed, we will enlist our PCORI partners to access and optimize use of these 
resources for dissemination.  
A particularly valuable asset for dissemination of this project is the Pepper Older Americans Independence 
Centers, which form a network of fourteen key academic institutions and thought leaders who are likely to be 
early adopters of this program if proven effective. Two other major resources for dissemination will be the 
recently formed PCORI Patient Powered Research Network (PPRN) and the Clinical Data Research Network 
(CDRN). Because this is a multifactorial fall-related injury prevention intervention, it will be important to 
determine the readiness of specific research findings for D&I through these networks. As best as can be 
gleaned from a priori-defined outcomes, D&I efforts should focus on communicating what works, and what 
does not work, particularly tailoring the message to key relevant stakeholder groups. The proper balance 
between benefits vs. potential risks must be struck and clear guidance provided to stakeholders.  
15. ORGANIZATIONAL FRAMEWORK OF AN INTERDISCIPLINARY TEAM OF INVESTIGATORS, 
PATIENTS, AND STAKEHOLDERS 
This program will be a cooperative agreement with substantial NIH and PCORI programmatic involvement 
anticipated throughout the project.  
The project is led by three joint PIs – Bhasin, Gill and Reuben. The PIs have the primary responsibility for all 
aspects of the study, but will accept close coordination, cooperation, and participation of NIA and PCORI staff. 
The Steering Committee is the primary high-level decision-making body for the study with overall responsibility 
for the final approval of the study protocol, monitoring the study’s progress, approving revisions to the protocol, 
and deciding whether to advance the study from protocol development and refinement to the implementation 
phase. Members of the steering committee include the three PIs, the Director of the Data Coordinating Center, 
a representative of PCORI, NIA scientific officer, two clinical trial site PIs, a nurse scientist, the Safety Officer, 
three content experts, and an IT and Data Management expert. Additionally, the NIA Program Officer, the 
Study Director, the Study’s Communications Director, the Study Manager, a PCORI Officer, and a patient 
representative will serve as nonvoting members. 
The Operations Committee is responsible for overall operational management and coordination of the entire 
project, synthesizing information from various committees, preparing and executing operational plans, 
identifying problems and disseminating information throughout the operation.  The Operations Committee 
includes the three Joint PIs, Director of the OAIC Coordinating Center, and the Study Director. 
15.1 Committees 
Table 8 displays the functions of the current committees. The committees include scientific chairs, other highly 
regarded experts in the area of falls prevention, and patient and stakeholder representatives.  The Committees 
conduct their business through regularly scheduled conference calls; their approved minutes are posted in the 
STRIDE Study Box. 
15.2 Reporting Structure 
As shown in Figure 2, the various committees, DCC, and IT Management Group report to the Operations 
Committee, which in turn reports to the Steering Committee, which is the highest decision making body. The 
leadership of NIA and PCORI interfaces with the Stride Study leadership through the Steering Committee or 
directly with the PIs through the Operations Committee. 
 

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38
Table 8.  Functions of the Committees  
Committee 
Committee Function  
 
Steering  
The primary high-level decision-making body for the study with overall responsibility for 
the final approval of the study protocol, monitoring the study’s progress, approving 
revisions to the protocol, and deciding whether to advance the study from protocol 
development and refinement to the implementation phase. 
Operations  
Consists of the three Joint PIs, OAIC Coordinating Center Director, and the Study 
Director. Responsible for overall operational management and coordination of the entire 
project, synthesizing information from various committees, preparing and executing 
operational plans, identifying problems and disseminating information throughout the 
study. 
Clinical Trial Sites  
Provides venue for bidirectional flow of information between site PIs and the study’s 
leadership. Provides high-level guidance for the trial’s implementation at the trial sites. 
Includes all site PIs. 
Screening and Recruitment 
Responsible for high-level guidance on screening and recruitment activities. 
Intervention  
 
Responsible for developing the protocols for the intervention, FCM evaluation and 
training, and overseeing the implementation of the intervention at the trial sites. 
Physical Components/ 
Rehabilitation Subcommittee  
Responsible for developing the protocols for physical intervention, training of the 
rehabilitation and exercise staff at sites, and evaluation of CBE programs. 
Self-management 
Subcommittee 
Responsible for developing programs to train FCMs and study staff to encourage patient 
self-management.  
Training Subcommittee 
Responsible for developing training plans and programs for the FCMs and physical 
intervention/ rehab staff at the sites. 
National Patient Stakeholders 
Council  
Responsible for developing protocols for patient and stakeholder engagement, 
overseeing the formation and training of local patient and stakeholder councils, providing 
input into protocol development and all aspects of trial’s implementation. 
Biostatistics  
Responsible for sample size estimation, power calculation, practice randomization, and 
data analyses. 
Data Management and IT 
Platform  
Responsible for building the IT infrastructure for data collection and management, staff 
training in data recording, building appropriate interfaces with the EHRs at sites to allow 
data collection, creating data forms, ensuring data security, and overseeing FCM 
software development. 
Assessments and Study 
Outcomes  
To develop the procedures for the baseline assessment, ascertainment of study 
outcomes and a plan for collection and analyses of outcomes data 
Protocol  
Develop the study protocol for the pilot and main study. 
Ancillary Studies  
To review the ancillary studies proposals and make recommendations to the Steering 
Committee and NIA on the approval of ancillary studies to the trial. 
Publication  
To review publications and major presentations from the study. 
 
15.3 Meeting Schedule and Functions of the Leadership 
The Operations Committee [three PIs, Study Director, and PI of the OAIC Coordinating Center] hold a 
conference call weekly to review progress, establish work objectives, and discuss operational problems.  The 
Steering Committee meets by conference call every two weeks to ensure integration and oversight. In addition, 
we held two investigator’s meetings in year 01, and a third meeting is planned in late May. We plan to hold an 
investigators’ meeting once yearly in subsequent years.  
When necessary, individuals from the broader group of Co-Investigators and/or co-chairs of various 
committees will join the Steering Committee with regard to specific agenda items.   
 
 

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39
Figure 2. The Organizational Structure of the STRIDE Study Team 
 
15.4 Additional Committees 
As implementation progresses, the PIs and Steering Committee will consider forming additional committees to 
include Publications and Dissemination, as well as several operational committees. These committees will be 
co-chaired jointly by senior investigators with content expertise. All committees will include patient/stakeholder 
representation. 
15.5 Integration of Patient and Stakeholders in the Trial’s Planning, Implementation, Analyses and 
Dissemination  
In accordance with the model set forth by Curtis et al (Figure 3),53 patient engagement will occur at two levels 
– locally, at the clinical trial sites, and nationally, at the central project management level. To provide 
integration between the local and national patient and stakeholder councils, the local councils at the 10 trial 
sites have chosen representatives to serve on the National Patient and Stakeholder Council (NPSC). The 
NPSC is comprised of 10 to 12 members, half of whom are patients. The NPSC is representative in terms of 
the type of stakeholder, sex, race, ethnicity, and geographic region. Each Local Council is engaging with 
Steering Committee
NIA Leadership
The Operations Committee
DSMB
Various Committees*
DCC
IT Team
Central Project 
Management Center
Trial Sites
PCORI Leadership
NIA – PCORI 
Partnership for Fall 
Injuries prevention
National and Local Patient 
and Stakeholder Councils
* Patients and stakeholders are also represented on all committees.

RANDOMIZED TRIAL OF A MULTIFACTORIAL FALL INJURY PREVENTION STRATEGY 
 
 
40
investigators at its respective 
trial site and reports to the 
NPSC. The NPSC engages 
with all committees, PIs and 
Co-Is.  
As described below, we have 
planned for a systematic and 
robust process of patient and 
stakeholder engagement 
throughout all phases of the 
study.   
The Year 1 Pilot Period 
focused on 1) development of 
local patient and stakeholder 
councils; 2) development of 
national patient and 
stakeholder council (NPSC; 3) 
training of investigators and 
stakeholders to work in 
partnership; 4) refining 
methods for eliciting patients’ 
and stakeholders’ voices, and 
5) setting up structures to 
assure patients and 
stakeholders engagement with 
investigators to: (a) formulate the final research questions; (b) finalize study design with attention to screening 
and recruitment of participants, the planned intervention, the comparators, and the outcomes; (c) monitor 
study’s progress and interim results; and (d) help disseminate the results of the study.   
15.5.1 Local Patient and Stakeholder Councils 
The criteria for selection of local patients and stakeholders are described in Table 9.  
 
Table 9.  Composition of the Local Patient and Stakeholder Councils (LPSCs). At least half the members of each 
local council are patients.  Not all stakeholders will be represented on every local council but there is broad representation 
from each of these stakeholder groups across the ten local councils. 
Term  
Number  
Definition 
Patients 
 2 to 3 
Have a history of a fall or fall related injury or are at risk for a fall or fall 
related injury, are from the local community served by the clinical study 
site, and have no specialized training or experience in health advocacy or 
health research. 
Caregiver  
1  
Have provided care as a nonhealth professional to a friend or family 
member who is at risk for falling or has experienced a fall or fall related 
injury.  
Public/Community 
1 to 2  
Representatives from the local geographic communities that the health 
systems of the clinical sites serve, e.g. YMCA. 
Engagement professional – health 
1 
Representative from local patient and family centered care programs from 
the clinical sites. 
Clinician  
1 
Those providing care at the sites in which the study will be done (clinical 
sites). (e.g. NPs, physicians, PT). 
Government 
1 
Representative of local or state health department. 
Advocate/consumer group 
1 
Local area agency on aging. 
Figure 3. The Conceptual Framework for Patient and Stakeholder 
Engagement (Based on model developed by Curtis et al.) 

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41
The chair of the NPSC and 2 patient advisors from the NPSC worked with trial site PIs to identify potential 
participants, assure representativeness (e.g. race, sex, ethnicity), and prepare invitations, which included 
processing group expectations, the importance of their authentic participation, and resources available to 
enable their participation (e.g. payment; e-mail access). Each Local Patient and Stakeholder Council (LPSC) 
designed their group to include 8 to10 members and a facilitator with experience in engaging patients and 
stakeholders in research. The Local Patient and Stakeholder Councils are being co-chaired by the facilitator 
and a patient stakeholder. Members of the NPSC travelled to all the trial sites to train the council members. 
15.5.2 National Patient and Stakeholder Council  
The NPSC is comprised of 10 to 12 persons, at least half of whom are patients (Table 10).  The members of 
each local council recommended individuals for inclusion in the NPSC, giving attention to diversity of 
stakeholder type, sex, race/ ethnicity, and geographic location.  The NPSC: 1) serves in a consultative capacity 
to local councils and site PIs, various work group committees and study leadership; 2) integrates the input from 
the 10 local councils and communicates that to the trial’s PIs and committees; and; 3) coordinated activities 
initially for a) formulating the final research questions; b) finalizing study design; c) monitoring study progress, 
and suggesting changes and editing of all participant-facing print materials and d) recommendations for 
disseminating the results. 
 
15.5.3 Training patients, stakeholders, and investigators  
During Year 1, investigators, patients and stakeholders underwent training, focusing on communicating what it 
means to be partners in patient-centered research. The training emphasized an authentic communication 
paradigm that builds and maintains trust, respect, and mutual understanding.  An interactive Partners in 
Research (PIR) program was used that is part of the University of Michigan CTSA (MICHR) and has been 
delivered to over sixty communities including patients, stakeholders and investigators.  During this training, the 
patients and stakeholders from the local council and the investigators from the trial site met to develop 
common understandings of research from the perspective of others and discussed methods for developing 
effective partnerships in addressing research issues related to injurious fall prevention. These discussions 
were led jointly by the NPSC chair and NPSC patient advisors. 
15.5.4 Engaging patients and other stakeholders as partners in all phases of the research:   
The bidirectional process of engaging patients and other stakeholders will take place in local councils and the 
NPSC throughout the duration of the project. Initially, the local councils are meeting monthly, until the LPSC’s 
have established a high functioning participatory group. The NPSC will continue to meet twice a month 
throughout the duration of the study. 
Table 10. Composition of the National Patient and Stakeholder Council (NPSC). The NPSC include 10 to 12 
members, at least half of whom will be patients.  
Term  
Number  Description 
Patients 
5 to 6 
Are from a local stakeholder group, have a history of a fall or fall related injury or are at risk for a 
fall or fall related injury, and have no specialized training or experience in health advocacy or 
health research.  
Caregiver  
1 to 2 
Are from a local stakeholder group and have provided care as a nonhealth professional to a 
friend or family member who is at risk for falling or has experienced a fall or fall related injury.   
Public/Community 
1 to 2 
Representatives from a Pepper Center Community group or CTSA Community Engagement 
group from the participating clinical sites. 
Engagement 
professional – health 
1 
Representatives from a patient and family centered care programs – may or may not be on a 
local stakeholder group. 
Clinician  
1 to 2 
Individuals who provide health care or related services to older adults on a regular basis (over 
80% in clinical care). 
Government 
2 
Representative from NIA/ PCORI. 
Advocate/consumer 
group 
1 
National Area Agency on Aging. 

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42
After the planning year, the local councils will focus on refining their trial sites’ local resources that support 
screening and recruitment strategies, the intervention(s), assessment and outcomes, and strategies for 
disseminating the trial’s findings. These local councils will provide recommendations to the NPSC and to site 
PIs and continually support the local Falls Care Manager(s). The NPSC will collate the information from all 
local councils and provide guidance to the PIs and various committees [See Figure 4]. 
15.5.5 Eliciting patients’ and stakeholders’ 
voices through focus groups 
To gain the patients’ and stakeholders’ 
perspectives on specific issues, the NPSC will 
continue to work with local councils to organize 
focus groups at each trial site. The local focus 
groups will be led by the facilitator and co-chair 
of the local council. Each of the local 
stakeholders will be asked to invite one or two 
individuals who have roles similar to theirs (e.g. 
patient, caregiver, clinician) to participate in a 
focus group. The focus groups will be planned 
for 10 participants. With the permission of the 
participants, focus groups will be tape-recorded 
and analyzed using standard qualitative 
methods.54 If focus group participants are 
averse to tape-recording conversations, a 
scribe will prepare a summary of the 
discussion. Topics for discussion will include 
overall study progress, review of interim 
analyses, and dissemination of the trial’s findings.  Focus group summaries will be provided to NPSCs, which 
will collate the findings from the 10 sites and communicate them to Joint-PIs and committee chairs.  
15.5.6 Monitoring the study’s progress 
The local councils and site investigators will meet quarterly to review study progress and address, collectively, 
any potential issues in implementation. These meetings will be led by the local facilitator. Summations of these 
meetings will be forwarded to the site PIs and the NPSC. The NPSC will review and collate the 
recommendations of the 10 local councils and communicate these to the Joint PIs and committee chairs to 
inform protocol revisions, which will be presented to the Steering Committee and DSMB for approval.   
15.5.7 Dissemination and implementation of study findings 
A Publication and Dissemination Committee (PDC) will be established to oversee the dissemination of the 
study findings. The PDC will include members of the NPSC and investigators with content expertise. This 
structure will allow the stakeholders and investigators to jointly address 1) how to disseminate the study 
findings to impact clinicians, patients, policy makers, communities, CMS and other payers; and 2) how study 
interventions can be scaled up for wider implementation. Also, local councils will work with site investigators to 
plan dissemination in their local communities. The patients and stakeholders can be effective particularly in 
influencing the policies of CMS and other payers, which can facilitate the adoption of the intervention. In 
addition to publications in scientific journals, the PDC will plan presentations at scientific meetings, and 
orchestrate presentations to stakeholders, the media, payers, and policymakers.    
15.5.8 Ongoing Evaluation and Feedback 
This study provides an outstanding opportunity for formative and summative evaluation of patient and other 
stakeholder engagement in research.  Formative evaluation will be performed by all stakeholders annually. We 
Figure 4. The organizational framework of the 10 Local 
Patient and Stakeholder Councils (LPSCs) at the trial sites 
and the National Patient and Stakeholder Council (NPSC). 
The LPSCs and NPSC will meet quarterly throughout the 
trial. The NPSC will collate the reports from the LPSC 
meetings and focus groups and communicate them to the 
Joint PIs and the Committee Chairs. Focus groups will 
address specific design issues, as described in the text. 
LPSC
LPSC
LPSC
LPSC
LPSC
LPSC
LPSC
LPSC
LPSC
LPSC
•
Quarterly Meetings of LPSCs
•
Focus groups
National Patient and 
Stakeholder’s Council (NPSC) 
Quarterly Meetings of NPSC
Joint PIs and Committee Chairs

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43
will use the Partnership Trust Tool Survey, developed by the CDC (www.cdc.gov/prc), to elicit stakeholders’ 
perceptions about 12 components of partnerships in research such as communication, willingness to listen to 
the ideas of others, relationship building, sharing of power and decision-making, truthfulness, and valuing of 
differences. These surveys will elicit information such as 1) what were the barriers to your engagement in this 
research; 2) what made the intervention helpful; 3) were there challenges in implementing the intervention in 
some groups of participants, such as ethnic groups and those living in rural areas; 4) what would you 
recommend to other investigators who plan to engage patients and stakeholders; 5) what would you 
recommend for large-scale use of the intervention(s) in your community; and 6) what are the lessons learned 
by engaging in this research. 
 

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44
16. REFERENCES 
1.   Sterling DA, O'Connor JA, Bonadies J. Geriatric falls: injury severity is high and disproportionate to 
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