Randomized Trial of Telehealth vs. Conventional Hearing Care Delivery in the ACHIEVE Study
Phase: NA
Conditions: Hearing Loss, Aging
Sponsor: Johns Hopkins University

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
1 
Randomized Trial of Telehealth vs. Conventional 
Hearing Care Delivery in the ACHIEVE Study 
(ACHIEVE-HIFU) 
 
Protocol 
 
Protocol Number:  IRB00284937 
ClinicalTrials.gov Number:  NCT05070429 
 
Principal Investigators: 
Frank R. Lin, MD PhD, Johns Hopkins University 
Victoria Sanchez, AuD PhD, University of South Florida 
Nicholas S. Reed, AuD PhD, Johns Hopkins University 
 
 
Funded by:  The National Institute on Deafness and Other 
Communication Disorders (NIDCD) 
 
Grant # R01DC019408 
 
 
V.1.3 June 5, 2024 
 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
2 
Summary of Changes from Protocol Version 1.2 to 1.3 
Minor changes to page numbering and formatting and minor corrections and clarifications were 
made throughout the document.  Substantive changes are highlighted in the below table. 
Affected section(s) 
Brief description of change 
Brief rationale for change 
2.1 Synopsis 
Updated the Outcomes and the 
Statistical Methods 
Updates were made to correspond 
with the final HIFU Statistical Analysis 
Plan 
3 Study objectives and 
end points 
Updated the list of secondary 
and exploratory outcomes 
List of outcomes were updated for 
consistency with the study’s final 
Statistical Analysis Plan 
7.1 Schedule of activities, 
Table 1 
Updated the footnotes previously 
noted as “Procedures that are 
intermittent based on protocol” 
The footnotes have been updated to 
provide details about when or why the 
procedures are or are not completed 
10.2 Adverse events 
Updated information in the SAE 
section to reflect previously 
approved changes to the DSMP 
These edits were missed during the 
previous update to reflect the study’s 
revised DSMP and are now being 
incorporated 
11.2 Analytic approach 
Updates were made to the list of 
confounders, and a description 
was added to account for a non-
normal distribution, continuous 
secondary outcomes, and for 
adjustments for multiple 
comparisons 
Updates were made to correspond 
with the final HIFU Statistical Analysis 
Plan 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
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Table of Contents 
1 
Statement of Compliance ................................................................................................ 5 
2 
Protocol summary ............................................................................................................ 5 
2.1 
Synopsis .......................................................................................................................... 5 
2.2 
Schema ........................................................................................................................... 8 
3 
Study objectives and endpoints ....................................................................................... 8 
4 
Background and rationale .............................................................................................. 10 
4.1 
Hearing health care ....................................................................................................... 10 
4.2 
ACHIEVE background ................................................................................................... 11 
4.3 
Preliminary studies of telehealth HHC ........................................................................... 11 
5 
Study population and eligibility ...................................................................................... 12 
5.1 
Eligibility ......................................................................................................................... 12 
5.2 
Recruitment and retention ............................................................................................. 13 
6 
Participant rights and confidentiality .............................................................................. 14 
6.1 
Informed consent ........................................................................................................... 14 
6.2 
Participant confidentiality ............................................................................................... 15 
7 
Study assessments and procedures ............................................................................. 16 
7.1 
Schedule of activities ..................................................................................................... 16 
7.2 
Hearing intervention assessment .................................................................................. 19 
7.2.1 
Intervention Check-Up .......................................................................................... 19 
7.2.2 
Utilization of hearing services ............................................................................... 19 
7.2.3 
International Outcome Inventory for Comprehensive Hearing Intervention .......... 19 
7.2.4 
Client-Oriented Scale of Improvement .................................................................. 19 
7.3 
Audiometric assessment ............................................................................................... 19 
7.3.1 
Air conduction audiometry ..................................................................................... 20 
7.3.2 
Bone conduction audiometry ................................................................................. 20 
7.3.3 
Tympanometry ...................................................................................................... 20 
7.3.4 
Word Recognition in Quiet .................................................................................... 20 
7.3.5 
Quick Speech in Noise (unaided) .......................................................................... 20 
7.4 
Social functioning and quality of life .............................................................................. 20 
7.4.1 
Center for Epidemiological Studies Depression Scale (CES-D) ........................... 20 
7.4.2 
Hearing Handicap Inventory for the Elderly - Screening Version .......................... 20 
7.4.3 
RAND-36 Health Survey ....................................................................................... 20 
7.4.4 
Social Network Index ............................................................................................ 21 
7.4.5 
UCLA Loneliness Scale ........................................................................................ 21 
7.4.6 
Hospitalizations ..................................................................................................... 21 
7.5 
Covariates ..................................................................................................................... 21 
7.5.1 
Health history questionnaire .................................................................................. 21 
7.5.2 
Neurologic history ................................................................................................. 21 
7.5.3 
Anthropometry ....................................................................................................... 21 
7.5.4 
Seated blood pressure .......................................................................................... 21 
7.5.5 
COVID impact questionnaire ................................................................................. 21 
7.5.6 
Telehealth acceptance questionnaires .................................................................. 21 
7.6 
Physical activity and physical functioning ...................................................................... 22 
7.6.1 
Baecke Physical Activity Questionnaire ................................................................ 22 
7.6.2 
Accelerometry ....................................................................................................... 22 
7.6.3 
Falls and mobility .................................................................................................. 22 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
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7.6.4 
Grip strength ......................................................................................................... 22 
7.6.5 
Short Physical Performance Battery (SPPB) ........................................................ 22 
7.7 
Dementia and MCI assessments ................................................................................... 22 
7.7.1 
Neurological interviews ......................................................................................... 23 
7.7.2 
Clinical Dementia Rating Scale (CDR) .................................................................. 23 
7.7.3 
Functional Assessment Questionnaire (FAQ) ....................................................... 23 
7.7.4 
Neuropsychiatric Inventory (NPI) .......................................................................... 23 
7.8 
Neurocognitive battery ................................................................................................... 24 
7.8.1 
Ensuring speech understanding test ..................................................................... 24 
7.8.2 
Mini-Mental State Exam (MMSE) .......................................................................... 24 
7.8.3 
Delayed word recall test (DWRT) .......................................................................... 24 
7.8.4 
Digit Symbol Substitution test (DSST) ................................................................... 24 
7.8.5 
Incidental learning ................................................................................................. 24 
7.8.6 
Trail Making Test Part A (TMT A) .......................................................................... 25 
7.8.7 
Trail Making Test Part B (TMT B) .......................................................................... 25 
7.8.8 
Logical Memory I and II ......................................................................................... 25 
7.8.9 
Digit Span Backwards ........................................................................................... 25 
7.8.10 
Boston Naming test ............................................................................................... 25 
7.8.11 
Word Fluency ........................................................................................................ 26 
7.8.12 
Animal Naming ...................................................................................................... 26 
7.8.13 
Telephone neurocognitive assessment ................................................................. 26 
7.9 
Characterization of participants who leave the study early ........................................... 26 
8 
Randomization ............................................................................................................... 27 
8.1 
Measures to minimize bias ............................................................................................ 27 
9 
Interventions .................................................................................................................. 28 
9.1 
All participants ............................................................................................................... 28 
9.2 
Telehealth hearing health care ...................................................................................... 28 
9.2.1 
Telehealth Session A ............................................................................................ 28 
9.2.2 
Telehealth Sessions B and C ................................................................................ 29 
9.2.3 
Asynchronous provider-to-participant telehealth communications ........................ 29 
9.3 
Conventional clinic-based hearing health care .............................................................. 29 
9.3.1 
Crossover to telehealth HHC delivery model ........................................................ 30 
10 
Safety monitoring ........................................................................................................... 30 
10.1 
Data and safety monitoring board ................................................................................ 30 
10.2 
Adverse events ............................................................................................................. 30 
11 
Statistical considerations ............................................................................................... 33 
11.1 
Sample size .................................................................................................................. 33 
11.2 
Analytic approach ......................................................................................................... 33 
12 
Data management ......................................................................................................... 34 
13 
Study sites and structure of the study team .................................................................. 36 
13.1 
Field centers ................................................................................................................. 36 
13.2 
Coordinating Center (CC) ............................................................................................. 36 
13.3 
Hearing intervention unit ............................................................................................... 36 
13.4 
Analysis and study governance site ............................................................................. 36 
13.5 
Single IRB ..................................................................................................................... 36 
13.6 
Study organization ........................................................................................................ 37 
14 
History of protocol amendments .................................................................................... 37 
15 
References .................................................................................................................... 40 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
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1 
Statement of Compliance 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the United States (US) Code of Federal Regulations (CFR) 
applicable to clinical studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 
312, and/or 21 CFR Part 812).  All personnel involved in the conduct of this study have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent forms, recruitment materials, and all participant materials will be 
submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both the 
protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
2 
Protocol summary 
2.1 
Synopsis 
Title 
Randomized Trial of Telehealth vs. Conventional Hearing Care 
Delivery in the ACHIEVE Study 
Short Title 
ACHIEVE-HIFU (ACHIEVE Hearing Intervention Follow-Up) 
Field Sites 
• 
George Comstock Field Center, Johns Hopkins Bloomberg School 
of Public Health, Washington County, MD 
• 
University of Mississippi Medical Center, Jackson, MS 
• 
University of Minnesota, Minneapolis, MN 
• 
Wake Forest University, Forsyth County, NC 
Other Study Sites 
• 
University of South Florida (hearing intervention unit) 
• 
Johns Hopkins University (analysis and study governance unit) 
• 
University of North Carolina Chapel Hill (coordinating center) 
Design 
Multi-site randomized trial comparing conventional in-person hearing 
health care (HHC) versus in-person HHC plus telehealth audiology 
sessions among existing hearing aid users. 
Sample Size and 
Population 
This study is predicated on an already established cohort of existing 
hearing aid users with a fixed sample size from the original Aging and 
Cognitive Health Evaluation in Elders (ACHIEVE) trial (N=490 hearing 
intervention cohort).  We conservatively estimate that N=400 
participants currently in the hearing intervention group will be recruited 
into this follow-up study. 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
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Main Eligibility 
Criteria 
To be eligible for the current study, participants must:  1) have been 
eligible for and participated in the hearing intervention arm of the 
ACHIEVE trial (see main original criteria below), 2) agree to be 
randomized to receive hearing care via continued conventional in-
person visits or conventional in-person care with the addition of 
telehealth audiology sessions.  Participants randomized to 
conventional in-person care only would also receive telehealth 
sessions after one year, and 3) agree to participate and able and 
willing to be followed for 2 years in the follow-up study. 
Original ACHIEVE criteria:  Community-dwelling adults aged 70-84 
years with mild to moderate audiometric hearing impairment, and free 
from substantial cognitive impairment at baseline. 
Objectives 
Primary:  
1. To compare the effect of the telehealth hearing health care (HHC) 
versus conventional HHC delivery models on hours of hearing aid 
use (primary outcome) at 1-year post-randomization. 
Secondary: 
2. To compare the effect of the telehealth HHC versus the 
conventional HHC delivery model on patient-centered hearing 
and communication outcomes, social functioning, and quality of 
life at 1-year post-randomization. 
3. To compare utilization of hearing services required by each HHC 
delivery model. 
4. To evaluate the association of the telehealth HHC intervention 
with changes in hearing aid use and patient-centered hearing and 
communication, social functioning, and quality of life measures 
from baseline to up to two years post-intervention.  
Outcomes 
Primary:  Average daily hours of hearing aid use at 1 year, as 
measured through objective hearing aid data logging.  If a participant 
wears a hearing aid in both ears, then the ear with the greatest 
number of hours logged will be selected. 
Key secondary:   
• 
Treatment satisfaction, as assessed by a single item from the 
International Outcome Inventory – Comprehensive Hearing 
Intervention (IOI-CHI) 
• 
Ability to hear for the primary communication goal, as assessed 
by a single item from the Client-Oriented Scale of Improvement 
(COSI) goals achievement questionnaire 
• 
Hearing-specific quality of life, as assessed by the Hearing 
Handicap Inventory for the Elderly Screening Version (HHIE-S) 
questionnaire 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
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Randomization and 
stratification 
1:1 random block randomization, stratified by degree of hearing loss 
(mild vs. moderate or greater), cohort (originally recruited to the 
ACHIEVE study from the Atherosclerosis Risk in Communities Study 
[ARIC] or de novo from the community), and field center to achieve 
balance among these factors between treatment arms.  Similar to 
ACHIEVE, spouse pairs will be randomized to the same treatment 
group. 
Study Interventions 
Conventional HHC:  Participants randomized to continued 
conventional HHC group will, for the first year of this study, continue to 
receive the same conventional, clinic-based hearing intervention 
received in the original ACHIEVE study, with clinic-based visits every 6 
months to reinforce self-management strategies and perform hearing 
aid checks.  In year two, participants randomized to continued 
conventional HHC will crossover to receive telehealth HHC. 
Telehealth HHC:  The telehealth HHC intervention allows for remote 
access to hearing health care services and continuous support of 
participants’ hearing loss needs via telehealth in addition to 
conventional clinic-based hearing booster sessions that occur every 6 
months.  Participants randomized to the telehealth HHC group will 
receive telehealth HHC for both years of the study. 
Participant Duration 
2 years, with data collection follow-up visits occurring every 6 months 
Study Duration 
5 years 
Statistical 
Methodology 
Primary:  The primary analysis compares hearing aid utilization 
between groups randomized to telehealth HHC versus conventional 
HHC delivery model under the intention-to-treat paradigm, analyzing 
individuals according to their random allocation, irrespective of the 
treatment received.  Consistent with best practices in clinical trials, we 
will assess the comparability of the randomized groups with respect to 
known confounders (e.g., recruitment source, site, level of hearing 
impairment, Quick Speech in Noise score, self-reported acceptance of 
telehealth at baseline, self-reported and objectively measured baseline 
hours of hearing aid use, self-reported baseline hours of hearing 
assistive technologies use, the number of days hearing log data was 
measured prior to randomization, and the number of visits prior to 
randomization at which a participant provided hearing logging data).  
These variables will be considered as covariates in all models. 
We will use a weighted regression model with an identity link to 
compare average daily hours of hearing aid use at 1-year post-
randomization between participants assigned to the telehealth HHC 
and conventional HHC.  To account for the non-normal distribution of 
the outcome, confidence intervals and p-values will be obtained using 
a bias corrected and accelerated bootstrap resampling procedure with 
10,000 replicates. 
 

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2.2 
Schema 
 
 
3 
Study objectives and endpoints 
The aims of the Randomized Trial of Telehealth vs. Conventional Hearing Care Delivery in the 
ACHIEVE Study (ACHIEVE Hearing Intervention Follow-Up, or ACHIEVE-HIFU) are: 
 
Primary aims 
1. To compare the effect of the telehealth HHC versus the conventional HHC delivery model 
on hours of hearing aid use (primary outcome) at 1 year post-randomization. 
 
Secondary aims 
2. To compare the effect of the telehealth HHC versus the conventional HHC delivery model 
on secondary outcomes of patient-centered hearing and communication outcomes, social 
functioning, and quality of life at 1 year post-randomization. 
3. To compare utilization of hearing services required by each HHC delivery model. 
4. To evaluate the association of the telehealth HHC intervention with changes in hearing aid 
use and patient-centered hearing and communication, social functioning, and quality of life 
measures from baseline to up to two years post-intervention. 
 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
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Primary outcome 
The primary outcome is average daily hours of hearing aid use obtained from objective hearing 
aid data logging at 1 year post-randomization.  If a participant wears a hearing aid in both ears, 
then the ear with the greatest number of hours logged will be selected. 
 
Secondary outcomes 
1. Treatment satisfaction, as assessed by a single item from the International Outcome 
Inventory – Comprehensive Hearing Intervention (IOI-CHI).  The IOI-CHI is an 
interviewer-administered scale that consists of 6 items where participants self-report 
satisfaction with the hearing intervention using a 5-point Likert scale.  A higher score 
indicates a more favorable outcome. 
2. Ability to hear for the primary communication goal, as assessed by a single item from the 
Client-Oriented Scale of Improvement (COSI) goals achievement questionnaire.  COSI 
goals are rated using a 5-point Likert scale.  A higher score indicates the participant is 
able to hear more of the time. 
3. Hearing-specific quality of life, as assessed by the Hearing Handicap Inventory for the 
Elderly Screening Version (HHIE-S) questionnaire.  The HHIE-S is an interviewer-
administered questionnaire that consists of 10 items.  Participants rate whether hearing 
loss affects them in different situations (yes, sometimes, or no).  The total score is the 
sum of all responses and ranges from 0 to 20, with higher scores indicating greater 
hearing issues. 
 
Exploratory outcomes 
Exploratory analyses may include, but are not limited to: 
1. The 5 remaining items from the IOI-CHI, as well as a composite score created by 
computing the mean across all 6 items. 
2. Ability to hear for the other two communication goals from the COSI goals achievement 
questionnaire, as well as a composite score created by computing the mean across all 3 
goals. 
3. Telehealth acceptance, as assessed by an interviewer-administered scale that consists 
of 5 items in which participants rate the ease of use or utility of telehealth equipment 
using a 5-point Likert scale.  A higher score indicates a more favorable rating.  Each item 
will be examined separately before being analyzed collectively as part of a composite 
score created by computing the mean across all 5 items. 
4. Subgroup analyses of the primary and secondary outcomes including, but not limited to, 
sex, race, and education.  Interactions between treatment assignment and subgroups 
will be tested relative to p < 0.10. 
5. The effect of treatment assignment on the total number of contacts between the provider 
and participant.  The total number of provider-participant contacts is quantified by the 
study audiologists using forms completed at every encounter.  In a supplemental 
analysis, the number of contacts will be examined across specific modalities, including 
face-to-face contact in a clinic, face-to-face contact outside of a clinic (e.g., home visits), 
and remote contact (e.g., video calls, phone calls, etc.). 
6. The effect of treatment assignment on the total time spent between the provider and 
participant.  The total number of minutes during which the provider and participant 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
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interacted is quantified by the study audiologists using forms completed at every 
encounter.  In a supplemental analysis, the number of minutes will be examined across 
specific modalities, including face-to-face contact in a clinic, face-to-face contact outside 
of a clinic, and remote contact. 
7. Estimating the linear and potentially nonlinear dose-response relationship between 
utilization of hearing services and hours of hearing aid use at one-year post-
randomization.  This will include testing the total number of contacts between the 
provider and participant, the total amount of time the provider and the participant spend 
interacting, and differences by modalities such as face-to-face contact in a clinic, face-to-
face contact outside of a clinic, and remote contact. 
8. Using mixed effects models to examine trends over time from randomization to the two-
year follow-up assessment.  Time will be defined categorically or continuously with a 
time spline specified at 12 months.  An interaction between treatment assignment and 
time will be included in the model to estimate the effect of participants in the 
conventional HHC treatment arm gaining access to telehealth services one-year post-
randomization. 
 
4 
Background and rationale 
4.1 
Hearing health care 
Age-related hearing loss in older adults fits the World Health Organization’s definition of a 
chronic health condition, with leading professional organizations recommending a 
comprehensive and multi-dimensional care process.1–3  In practice, however, hearing health 
care is predominately delivered via an acute care model that is biomedically focused, clinician-
led, and device-centered.4  Beginning with the initial clinical encounter, the case histories 
obtained by audiologists often focus on the identification of underlying biomedical issues, with 
little dialogue focused on the person’s psychological or functional difficulties or psychosocial 
concerns.5  The application of a biomedical framework to the clinical decision-making process is 
typically then reaffirmed throughout subsequent clinical activities, rather than the application of a 
comprehensive, multi-dimensional model of HHC advocated by professional organizations that 
includes counseling, education, and coaching aimed at improving self-efficacy and locus of 
control, within a self-management framework.5,6  Although such non-technological activities are 
associated with positive outcomes, they are not routinely offered by audiologists.7 
 
Perhaps not surprisingly, current rates of hearing aid use among older adults with hearing loss 
in the U.S. are <20%, and rates of discontinuation of hearing aid use among older adults are 
high and estimated to be >30%.8–11  Telehealth delivery of HHC is a form of remote service 
delivery that makes use of smartphones, tablets, and computers for patients to access health 
care services away from a clinic, commonly from home.  Telehealth can be used to deliver 
services to adults with hearing loss including ongoing self-management support.12  While much 
research has focused on the influence of individual patient characteristics, attitudes, and beliefs 
on lack of hearing aid uptake and continued hearing aid use,13–17 there is increasing recognition 
that the current acute-care, clinic-based HHC model may itself be a leading contributor to low 
hearing aid uptake and utilization rates.4,18–20  Technological innovations in telecommunications, 
particularly with the widespread availability of smartphones, tablets, and broadband internet 
access, could enhance the accessibility of best practice models of HHC through facilitating 
ongoing delivery of self-management support services outside the clinical setting.21,22 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
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4.2 
ACHIEVE background 
ACHIEVE (ClinicalTrials.gov identifier:  NCT03243422; NIA R01AG055426, R01AG060502; 
MPIs:  Lin/Coresh) is a first-in-kind randomized trial to investigate if hearing loss treatment can 
reduce cognitive decline in older adults with hearing loss.  Recruitment actively began in 
January 2018 and ran through October 2019, with ACHIEVE enrolling 977 (~10/week) 
cognitively normal older adults with hearing loss, aged 70-84 years.  Participants were 
randomized 1:1 to a clinic-based, best-practices hearing intervention (hearing needs 
assessment, fitting of hearing devices, education/counseling; N=490) or a successful aging 
education intervention (individual sessions with a health educator covering healthy aging topics; 
N=487).  Semi-annual follow-up visits for three years assessed cognitive functioning and 
secondary outcomes. 
 
The ACHIEVE trial is nested within the Atherosclerosis Risk in Communities Neurocognitive 
Study (ARIC-NCS).  ARIC is a large, biracial prospective cohort study that enrolled 15,792 
participants aged 45-64 years from four US communities in 1987-1989:  Jackson, MS, Forsyth 
County, NC, Washington County, MD, and Minneapolis, MN.  The Jackson cohort was entirely 
African-American, and the Forsyth County site was about 15% African-American, with other 
participants being primarily white.  ARIC participants have received multiple assessments of 
cardiovascular risk factors, measurement of microvascular and macrovascular markers, 
cognitive testing, PET amyloid, and brain MRI over the last 30 years.  The ARIC study is well 
described with over 1700 papers published in peer-reviewed journals.23  The ACHIEVE-HIFU 
study brings together a multidisciplinary consortium of established investigators and leverages 
the existing research infrastructure, scientific expertise, and well-characterized participant 
cohort of ARIC-NCS.  The 977 participants in ACHIEVE were recruited from the existing ARIC-
NCS cohort (N=238) and de novo from the surrounding communities (N=739). 
 
4.3 
Preliminary studies of telehealth HHC 
Our preliminary studies to assess the feasibility of telehealth HHC delivery were guided by 
published recommendations for adapting manualized interventions.24  We began with an online 
survey of the ACHIEVE study audiologists to determine whether or not components of the 
conventional hearing intervention could or should be provided via telehealth.  Audiologists’ 
responses guided decisions regarding the inclusion of procedures at specific points in time over 
the course of intervention.  The results revealed that after the initial clinic-based sessions, many 
follow-up procedures and counseling could be delivered remotely.  We used the audiologists’ 
responses to help develop our multi-site fidelity monitoring plan for implementation of a 
manualized telehealth-supported HHC model for ACHIEVE-HIFU.  Our team then adapted the 
parent ACHIEVE manualized hearing intervention to incorporate telehealth to support long-term 
HHC. 
 
We conducted an initial feasibility study of the adapted telehealth hearing intervention among a 
convenience sample of 10 first-time hearing aid users, 6 male and 4 female, aged 70-91 years 
old, who were sampled from a clinical population at the University of South Florida in 2019.  
Inclusion and exclusion criteria matched that in the parent ACHIEVE trial, with the additional 
requirement of access to a smartphone.  During our pilot study, we identified two major barriers 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
12 
to successful remote HHC delivery:  1) availability of a compatible smartphone/tablet with 
adequate internet connection speed, and 2) participant unfamiliarity with telehealth HHC and 
challenges with how to use a telehealth platform.  In order to address these barriers, we 
incorporated the GrandPad device into our ACHIEVE-HIFU telehealth protocol.  The GrandPad 
is an internet-enabled tablet that was specifically designed for use by older adults, has been 
effectively implemented at scale for telemedicine, and comes with manufacturer support 
services to ensure that older adults can effectively use the device.  
 
5 
Study population and eligibility 
This study is predicated on an already established cohort with a fixed sample size from the 
original ACHIEVE trial (N=490 for the clinic-based hearing intervention cohort).  All participants 
currently in the ACHIEVE hearing intervention group will be invited to join this follow-up study, 
and accounting for loss to follow up and refusal to continue participating, we conservatively 
estimate that N=400 participants will be recruited into this follow-up study. 
 
5.1 
Eligibility 
To be eligible for the current study, participants must meet the following criteria: 
1. Eligible for and participated in the hearing intervention arm of the ACHIEVE trial (see 
original criteria below) 
2. Agree to be randomized to receive hearing care via either a telehealth or conventional 
delivery model for the first year before being offered telehealth options, and 
3. Agree to participate and able and willing to be followed for two years in the follow-up 
study. 
ACHIEVE participants who have developed cognitive impairment are eligible for ACHIEVE-
HIFU if they are willing to participate and are consented with a proxy (see section 6.1 below). 
Original ACHIEVE inclusion criteria: 
• 
Age 70-84 years 
• 
Community dwelling, fluent English speaker 
• 
Availability of participant in area for study duration 
• 
Adult-onset hearing impairment, defined as four-frequency pure tone average (PTA, 0.5-
4kHz, better ear) ≥ 30 dB & < 70 dB 
• 
Speech recognition scores in quiet ≥ 60% in better ear 
• 
MMSE ≥ 23 for high school degree or less; ≥ 25 for some college or more 
Original ACHIEVE exclusion criteria: 
• 
Reported disability in ≥ 2 activities of daily living (ADLs) 
• 
Vision impairment (worse than 20/63 on MN Near Vision Card) 
• 
Self-reported use of a hearing aid in the past 1 year 
• 
Medical contraindication to use of hearing aids (e.g., draining ear) 
• 
Unwilling to wear hearing aids on daily basis 
• 
Conductive hearing impairment with air-bone gap > 15 dB in two or more contiguous 
frequencies in both ears 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
13 
 
5.2 
Recruitment and retention 
The parent ACHIEVE cohort has already been recruited, and all participants assigned to the 
hearing intervention (N=490) in the parent study presenting for their final 3-year visit and who 
are willing and able to be followed for an additional two years will be eligible for inclusion in this 
proposed study.  We expect that nearly all participants will choose to enroll in this follow-up 
study for the following reasons:  1) Continued enrollment in the study ensures that participants 
will have continued long-term access to free care and management of their hearing aids with 
their study audiologist, with whom they have an established relationship (in contrast, 
participants would otherwise be responsible for covering on their own future costs related to 
replacement/repair of their hearing technologies and follow-up visits with another audiologist); 2) 
All participants will be provided with a free GrandPad for use for the duration of their 
participation in this follow-up study; and 3) Participants have been strongly engaged with this 
study, as evidenced by current rates of study retention, which is likely driven by the immediate 
and tangible benefits that the study provides to them.  We will also continue to use retention 
strategies for ACHIEVE participants that been highly effective to date.  In brief, some of these 
strategies include:  provision of transportation to sessions and home visits as needed, mailed 
newsletters, birthday and holiday cards, reminder cards and phone calls, small study incentives 
(e.g., tote bags, mugs, calendars, etc.), and meals/snacks provided at study visits.  
 
The following procedures are also implemented in order to enhance retention:   
• When scheduling sessions, participants will be asked about their preferred time and date 
• When scheduling in-person clinic visits, participants will be asked about: 
o How participants prefer to get to the clinic visit 
o Need for assistance getting to or moving around the clinic  
o Existence of any medical conditions (e.g., diabetes, dietary restrictions) which 
might affect the examination and/or type of snack provided 
• 
Reminder calls will be placed and/or reminder packets will be mailed to the participant 
prior to the scheduled appointment as needed, confirming the study session date and 
time 
• 
Free parking is provided to all participants for in-person sessions 
• 
Participants will be reimbursed for travel costs, or transportation will be covered for a 
participant if he/she is not able to drive and/or obtain a ride to attend a study visit 
• 
Participant study incentives will include study-related items (GrandPad device, pens, 
bags, mailed holiday cards, etc.) and/or modest payments (~$20 to ~$40) for 
participating in each study visit [individual field sites will determine the participant 
incentives to provide based on their previous experience and knowledge of their 
participants and community] 
• 
Participants will be contacted by telephone and/or mail to reschedule the appointment if 
participants fail to arrive for a scheduled appointment or cancel their appointment to 
encourage continued participation and to identify and overcome barriers to participation 
• 
Home or telephone-based visits by study staff will be conducted as necessary when 
participants may be physically unable to come to the field site (e.g., from illness or injury) 
[these visits will be informed by the experiences of study staff in performing such visits in 
the parent ACHIEVE and ARIC studies] 
 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
14 
Each no-show case will be individually reviewed by study field site staff.  Efforts to engage the 
participant will include a combination of telephone contacts, letters, and the possibility of offering 
an abbreviated visit.  Field site staff, in consultation with the study coordinator and/or field site PI 
and/or hearing intervention unit/analysis and study governance unit, will determine how long to 
continue contact efforts.  A participant will only be considered “withdrawn” if he/she explicitly 
requests to withdraw from the study.  Participants are free to refuse, or re-enter the study 
protocol after refusal, at any time. 
 
6 
Participant rights and confidentiality 
6.1 
Informed consent 
A signed consent form is obtained from each participant by trained study personnel. The 
consent form describes the purpose of the study, how randomization works, the procedures to 
be followed, and the risks and benefits of participation.  The consent process informs a 
volunteer about the study, indicates that participation is voluntary, and that the participant has 
the right to stop at any time.  Risks are enumerated in the informed consent form and described 
orally during the consent process. 
 
The purpose of the informed consent form is: 
• 
To inform the prospective participant as much and as accurately as possible about: 
o The procedures involved in the study 
o What is expected of participants who consent to enroll 
o What the study can and cannot provide to the participant 
o What are the reasonable risks and benefits 
o What are the alternatives to participation 
• 
To document the participant’s consent to participate in all of the respective study 
procedures 
• 
To provide a prospective participant with a legal document summarizing the study and 
his or her rights as a study participant 
• 
To provide the participant with ongoing explanations and continuing information that help 
the participant decide whether to begin or continue in the research study 
 
Re-obtaining consent in the event of consent changes 
• 
If substantive changes to the consent form occur after the participant has signed the 
consent form at the randomization visit, the participant will be informed of the changes 
prior to their next study visit or interaction. 
• 
Whenever possible and permitted by the IRB, verbal re-consent will be obtained from the 
participant and documented by study staff in the participant’s chart. 
• 
If written re-consent is required for changes to the consent form, re-consent can occur in 
person or remotely.  Remote consent would be obtained by emailing or mailing two 
copies of the consent form to the participant, having trained study personnel review the 
updated consent form, noting the changes, ensuring the participant understands the 
changes, and asking the participant to sign one copy of the form and mail it back.  Upon 
receipt, the study personnel who obtained consent would sign the form and document 
the consent process in a note in the participant’s chart. 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
15 
 
Re-obtaining consent in the event of cognitive impairment 
• Although those with dementia were not enrolled at baseline of the parent ACHIEVE trial, 
given the age of the cohort, some participants may have developed or may in the future 
develop cognitive impairment over the course of the study.  Participants determined to 
have significantly reduced cognitive capacity and who wish to take part or remain in this 
follow-up study will be re-consented with consent from a designated proxy. 
• If re-consent with a proxy is required during the course of the follow-up study, the re-
consent may occur in person or remotely.  Remote consent would be obtained by mailing 
two copies of the consent form to the proxy, having trained study personnel review the 
consent form with the proxy and participant over the telephone (answering questions and 
ensuring understanding), and having the proxy and participant sign one copy of the form 
and mail it back.  Upon receipt, the study personnel who obtained consent would sign the 
form and document the consent process in a note in the participant’s chart. 
• We will use procedures established by the parent ACHIEVE and ARIC studies to classify 
decision-making capacity.  Given the minimal risk associated with the study procedures, 
relatively conservative criteria will be used to trigger re-consent with a proxy.  These 
criteria include:  (1) a diagnosis of dementia based on cognitive testing at any of the 
study sessions, or (2) judgment of our trained staff at the time of a study session.  These 
criteria adhere to the published recommendations of the Alzheimer’s Association.25 
 
6.2 
Participant confidentiality 
Data from the ACHIEVE-HIFU study are used only in aggregate, and no identifying 
characteristics of individuals will be published or presented.  Per the existing parent study 
(ACHIEVE and ARIC) protocols, results of select testing (weight, body mass index, and blood 
pressure) are given to participants, and they can choose to share those data with their health 
care provider.  Study results of depressive symptoms, blood pressure, or cognition, which may 
indicate the need for referral for medical care, will be provided to participants, who are 
encouraged to share the results with their private physician.  If participants have given 
permission, the results may also be sent to participants’ private physicians.  Information, 
including results of testing to be shared with a participant’s primary care physician, is not 
released without written permission of the participant, except as necessary for monitoring by 
IRB. 
 
Confidentiality of data is maintained by using research identification numbers that uniquely 
identify each individual.  This study utilizes safeguards established as part of the parent studies 
(ARIC and ACHIEVE) to ensure the security and privacy of participants’ study records.  
Research records are kept in locked file cabinets within locked rooms at the study site.  Only 
selected study personnel will have access to participants’ study records on a need-to-know 
basis.  Data are stored on password-protected computers with regularly updated virus software.  
Identifying information is only kept in the files where it is necessary for the conduct of the study 
and linkage to other files.  In analysis files, study IDs only are used to identify participants.  
 
In compliance with the Health Insurance Portability and Accountability Act (HIPAA) and the 
Standards for Privacy of Individually Identifiable Health Information of the Department of Health 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
16 
and Human Services, study staff access protected health information (PHI) and medical records 
only after receiving signed informed consent or a HIPAA waiver of authorization.  Participants’ 
medical records that are obtained for review and abstraction are kept in a locked cabinet that is 
separate from other file cabinets.  Only selected study personnel have access to these files. 
 
7 
Study assessments and procedures 
As part of this study, participants will complete interviews, questionnaires, audiometric 
evaluations, neurocognitive assessments, and measures of physical functioning that mirror 
those completed as part of the parent ACHIEVE trial.  To reduce participant burden, data from 
the final visit in the parent ACHIEVE trial (year 3 follow-up) will serve as baseline data for this 
follow-up study.  The schedule is shown in 7.1 and descriptions of each of the activities, 
evaluations, or assessments are provided in the sections that follow the table.  Full details on 
data collection and measurements can be found in the Manual of Procedures. 
 
7.1 
Schedule of activities 
Table 1 details which data will be gathered and when.  Data collection visits may be split across 
multiple days or multiple settings (clinic visits, home visits, telephone contacts, or video calls) to 
meet the needs of our participants.  Some items related to exploratory outcomes might be 
dropped based upon participant burden, scientific considerations, or available resources. 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
17 
Table 1. Schedule of Activities and Evaluations 
Follow-up visit Baseline 
Random-
ization 
visit 
Telehealth Sessions 
Initial Telehealth 
Randomized HHC arm only 6-month Year 1 
(12mo) 
Telehealth Sessions 
Initial Conventional 
Randomized HHC arm only 
18-
month  
Year 2 
(24mo) 
Aa 
B 
C 
Ab 
B 
C 
Visit relative to parent 
ACHIEVE Trial (approx.) 
Yr 3 
(36mo) 
-- 
-- 
Yr 3.5 
(42mo) 
Yr 4 
(48mo) 
-- 
Yr 4.5 
(54mo) 
Yr 5 
(60mo) 
Randomization 
Informed consent 
 
X 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
GrandPad distribution 
 
X 
 
 
 
 
 
 
 
 
 
 
Hearing Intervention 
GrandPad instructions for 
telehealth 
 
 
X 
 
 
 
 
X 
 
 
 
 
Intervention check-up 
X 
 
 
 
 
 
 
 
 
 
 
 
HIFU Intervention check-up 
 
X 
Xc 
X 
X 
X 
X 
Xc 
X 
X 
X 
X 
International Outcome 
Inventory for Comprehensive 
Hearing Intervention 
X 
 
 
 
 
X 
X 
 
 
 
X 
X 
Client-Oriented Scale of 
Improvement (COSI) goal 
setting 
 
X 
 
 
 
 
 
 
 
 
 
 
COSI goals achievement 
 
 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
Audiometry 
Air conduction audiometry 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Bone conduction audiometry 
X 
 
 
 
 
 
Xd 
 
 
 
 
Xd 
Tympanometry 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Word Recognition in Quiet 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Quick Speech in Noise 
(unaided) 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Social Functioning and Quality of Life Outcomes 
CES-D Scale 
X 
 
 
 
 
X 
X 
 
 
 
 
X 
Hearing Handicap Inventory 
for the Elderly - Screening 
Version 
X 
 
 
 
 
 
X 
 
 
 
 
X 
RAND-36 Health Survey 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Cohen Social Network Index 
X 
 
 
 
 
 
X 
 
 
 
 
X 
UCLA Loneliness Scale 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Hospitalizations 
X 
 
 
 
 
X 
X 
 
 
 
X 
X 
Qualifying (S)AE 
assessment 
X 
 
 
 
 
X 
X 
 
 
 
X 
X 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
18 
Follow-up visit Baseline 
Random-
ization 
visit 
Telehealth Sessions 
Initial Telehealth 
Randomized HHC arm only 6-month Year 1 
(12mo) 
Telehealth Sessions 
Initial Conventional 
Randomized HHC arm only 
18-
month  
Year 2 
(24mo) 
Aa 
B 
C 
Ab 
B 
C 
Covariates 
Health history 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Neurologic history 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Anthropometry 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Seated blood pressure 
X 
 
 
 
 
 
X 
 
 
 
 
X 
COVID impact questionnaire 
X 
 
 
 
 
X 
X 
 
 
 
X 
X 
Telehealth acceptance pre-
intervention (TAP) 
 
X 
 
 
 
 
Xe 
 
 
 
 
 
Telehealth acceptance 
follow-up (TAF) 
 
 
 
 
 
Xf 
Xf 
 
 
 
X 
X 
Other Data Collection 
Baecke activity questionnaire 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Accelerometry 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Falls and mobility 
questionnaire 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Grip strength 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Short Physical Performance 
Battery 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Clinical Dementia Rating 
Scale - Participant (CDP) 
X 
 
 
 
 
 
X 
 
 
 
 
X 
Dementia/MCI evaluation if 
applicable (CDI, CDS, NPI) 
Xg 
 
 
 
 
 
Xg 
 
 
 
 
Xg 
Abbreviated neurocognitive 
batteryg 
 
 
 
 
 
X 
 
 
 
 
X 
 
Full neurocognitive batteryh 
X 
 
 
 
 
 
X 
 
 
 
 
X 
aSession A for those randomized to the telehealth HHC delivery arm will occur in-person, often at the end of the randomization visit 
bSession A for those initially randomized to the conventional HHC delivery arm will occur in-person, often at the end of the Year 1 visit 
cHIFU Intervention check-up only done during Session A if Session A is not the same day as the Randomization Visit (for those randomized to 
the telehealth group) or the Year 1 Visit (for those randomized to the conventional group) 
dOnly required if there has been a change in pure tone air conduction 
eConventional group only 
fTelehealth group only, and only if any telehealth sessions have been completed since the last visit 
gCollected if a participant is selected for informant interview, identified on the Selected to Stage 2 CDART report 
gEnsuring Speech Understanding (ESU) and MMSE only 
hESU, MMSE, Delayed Word Recall Test, Digit Symbol Substitution Test, Incidental Learning, Trail Making Test Part A and Part B, Logical 
Memory I and II, Digit Span Backward, Boston Naming Test, Word Fluency (FAS), and Animal Naming 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
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7.2 
Hearing intervention assessment 
7.2.1 Intervention Check-Up 
The ACHIEVE-HIFU Intervention Check-Up includes assessments of the following components 
related to the hearing intervention at the in-person semi-annual and annual visits, and some of 
the components, as noted below, during both scheduled and unscheduled remote encounters. 
• 
Hearing aids:  usage of all hearing aids is documented [all contacts] 
• 
Real-ear aided response:  real-ear measure to verify the gain and output of hearing 
aids [in-person visits only; as needed] 
• 
Speech intelligibility index:  a calculated estimate from the real-ear measurements 
that indicates the amount of the speech signal available to the participants when wearing 
their hearing aids [in-person visits only; as needed] 
• 
Hearing aid data logging:  hearing aid use is obtained from the device data log within 
the hearing aid manufacturer software, including the total hours of use and average 
hours of use per day [in-person visits only] 
• 
Hearing assistive technologies (HAT):  usage of HATs is documented [all contacts] 
• 
Quick speech in noise (QuickSIN; aided):  assesses speech recognition in noise 
utilizing the hearing aids, where sentences are presented in the presence of background 
noise, and the participant repeats back what they heard [in-person annual visits only] 
7.2.2 Utilization of hearing services 
Each provider-participant contact and its duration, along with type/mode of contact, will be 
documented by the study audiologists.  Both scheduled contacts (documented as part of the 
Intervention Check-Up) and unscheduled contacts will be documented. 
7.2.3 International Outcome Inventory for Comprehensive Hearing Intervention 
The International Outcome Inventory for Comprehensive Hearing Intervention (IOI-CHI) is a 
brief, 6-item measure adapted from the International Outcome Inventory for Hearing Aids (IOI-
HA)26 .  The IOI-CHI is used to determine benefit from the hearing intervention following a 
sustained period of regular use. 
7.2.4 Client-Oriented Scale of Improvement 
The Client-Oriented Scale of Improvement (COSI)27 is a clinical tool developed by National 
Acoustic Laboratories (NAL) for outcomes measurement.  It is an assessment questionnaire 
used to document a participant’s goals/needs and progress towards achieving those goals. 
 
7.3 
Audiometric assessment 
The audiometric diagnostic battery will be conducted by a trained audiologist for all participants, 
regardless of HHC delivery assignment.  The diagnostic battery is based on current American 
Academy of Audiology guidelines.28  Based on the audiologist’s professional discretion, some 
components of the assessment can be omitted.  Cerumen management by the study audiologist 
will be performed as needed.  Participants with more severe cerumen impactions that cannot be 
easily cleared by the study audiologist will be provided with over-the-counter cerumenolytic ear 
drops (e.g., Debrox, Murine) and advised to follow-up with their primary care provider or an 
otolaryngologist.  

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
20 
7.3.1 Air conduction audiometry 
Behavioral measurement of minimally perceptible tones tested across the frequencies most 
important for speech communication delivered through headphones. 
7.3.2 Bone conduction audiometry 
Behavioral measurement of minimally perceptible tones tested across the frequencies most 
important for speech communication delivered through a bone oscillator, which allows 
determination of a sensorineural hearing loss free of middle ear problems.  Based on the 
audiologist’s professional discretion, this measurement can be omitted if hearing is stable since 
last evaluation.  
7.3.3 Tympanometry 
Objective measurement that determines integrity of the tympanic membrane/ossicles and 
assists in determination of a sensorineural hearing loss free of middle ear problems. 
7.3.4 Word Recognition in Quiet 
Confirms that the speech perception abilities are consistent with a hearing loss that can be 
helped through traditional hearing aid intervention.29 
7.3.5 Quick Speech in Noise (unaided) 
The QuickSIN30,31 is a speech-in-noise test that measures the signal-to-noise (SNR) necessary 
for a listener to correctly identify 50% of key words on sentences presented in a babble 
background noise.  A listener’s abilities to understand speech in noisy backgrounds cannot be 
predicted by the audiogram, and this measure provides a tool to counsel the participant on 
realistic expectations for success with hearing aids and guides intervention decisions regarding 
hearing assistive technology (e.g., remote FM microphone). 
 
7.4 
Social functioning and quality of life 
7.4.1 Center for Epidemiological Studies Depression Scale (CES-D) 
The CES-D Short Form is a 12-item form to assess depressive symptoms, derived from the 
original 20-item CES-D.37  In addition to a reduced administration time and clearer response 
options (relative to the 20-item version), the Short Form is highly correlated with the original (r > 
.94), has a high internal consistency, retains the same factor structure as the original, and has a 
similar positive predictive value as a screening tool for identifying clinical depression.  The 
questionnaire is administered by interview, and is scored 0-24. 
7.4.2 Hearing Handicap Inventory for the Elderly - Screening Version 
This is an interviewer-administered questionnaire to gather data on the perception of the impact 
of hearing loss.39  This questionnaire assesses the social and emotional components of 
perceived hearing impairment such as embarrassment, and limits on personal and social life.  
7.4.3 RAND-36 Health Survey 
The 36-item RAND Health Survey, assesses health-related quality of life.40  It is a generic 
measure, as opposed to one that targets a specific age, disease, or treatment group. 

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7.4.4 Social Network Index  
The Cohen Social Network Index (SNI) is an interviewer-administered questionnaire to gather 
social network data.41  The Social Network Index evaluates two outcome variables:  1) Social 
Network Diversity – number of social roles in which the participant had regular contact with 
others at least once every 2 weeks, and 2) People in Social Network – total number of people 
with whom the participant had regular contact (at least once every 2 weeks). 
7.4.5 UCLA Loneliness Scale 
This interviewer-administered questionnaire42 measures subjective ratings of social isolation 
and loneliness (e.g., lacking companionship, feeling left out, and isolated from others, among 
others). 
7.4.6 Hospitalizations 
This interviewer-administered questionnaire records recent hospitalizations since the last time of 
study contact. 
 
7.5 
Covariates 
7.5.1 Health history questionnaire 
This is an interviewer-administered questionnaire that documents a number of chronic diseases 
or conditions (e.g., hypertension, diabetes, stroke, Parkinson’s disease, osteoporosis, among 
others). 
7.5.2 Neurologic history  
This questionnaire includes items about past neurologic diagnoses and treatments.  This 
information will be used as possible covariates and by MCI/dementia adjudicators.  
7.5.3 Anthropometry 
Participant height and weight will be measured using standardized study protocols from the 
parent studies (ARIC/ACHIEVE).  Anthropometric measures include height, weight, waist and 
hip circumference, and body fat. 
7.5.4 Seated blood pressure 
Seated systolic and diastolic blood pressure will be measured using standardized study 
protocols from the parent studies (ARIC/ACHIEVE). 
7.5.5 COVID impact questionnaire 
This brief questionnaire asks questions about how the coronavirus pandemic, or COVID-19, has 
affected the participant. 
7.5.6 Telehealth acceptance questionnaires 
Questions assess the participant’s comfort with and acceptance of telehealth HHC both prior to 
start of the telehealth intervention and after starting the telehealth intervention. 
 

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22 
7.6 
Physical activity and physical functioning 
7.6.1 Baecke Physical Activity Questionnaire 
This interviewer-administered questionnaire38 measures the frequency and duration of self-
reported activities.  This questionnaire asks about habitual physical activities including sport-
related activities during leisure time, non-sport related physical activity during leisure time, and 
television viewing. 
7.6.2 Accelerometry 
Physical activity is objectively assessed using the Actigraph Link accelerometer, an FDA 
approved, triaxial, water-resistant, wrist-worn device that can be worn 24 hours a day, 
continuously measuring intensity, duration, and frequency of physical activity.  Participants will 
be fitted with the device during their clinic visit and asked to continue wearing the device at all 
times for the subsequent 7 days43.  Participants will be asked to wear the accelerometer at 
baseline and again at follow-up to detect differences in physical activity and sedentary 
behaviors.  
7.6.3 Falls and mobility 
This interviewer-administered questionnaire records living circumstances, self-reported physical 
ability, fatigue, and falls. 
7.6.4 Grip strength 
Grip strength will be measured using standardized study protocols from the parent studies 
(ARIC/ACHIEVE).  Grip strength is objectively assessed with a handheld dynamometer.  After a 
practice trial, participants are asked to complete two trials, squeezing as hard as possible, with 
a 15-20 second rest between trials.  Grip strength exclusion is limited to those who have had 
surgery on both hands or on both wrists in the previous 3 months.  If only one side is affected, 
the unaffected side is tested.  The test can be performed if the participant has a current flare-up 
of pain in their wrist or hand, for example arthritis or tendonitis.  This information is recorded on 
the data collection form. 
7.6.5 Short Physical Performance Battery (SPPB) 
The Short Physical Performance Battery44 will be conducted using standardized study protocols 
from the parent studies (ARIC/ACHIEVE).  The SPPB is a series of physical performance tests 
designed to assess lower extremity function in older adults.  The SPPB ranges in score from 0-
12; higher scores indicate better function.  The total score is the sum of 3 component scores:  
chair stands, balance, and 4-meter walk gait speed; each component score ranges from 0-4. 
Exclusion from any performance test is based on examiner assessment or participant concerns 
that the test would be unsafe.  Walking aids are allowed during the 4-meter walk only, if 
participants feel they are necessary. 
 
7.7 
Dementia and MCI assessments 
A syndromic diagnosis of MCI and dementia will be determined and used as secondary 
outcomes.  Current criteria for MCI35 and dementia,36 which prominently included investigators 
for this project, are now well-established and have been employed successfully in ARIC-NCS 
and ACHIEVE.  Details of the diagnostic procedures and normative data have been published 
and are enumerated in the Manual of Procedures.  Briefly, MCI and dementia syndromic 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
23 
diagnoses are determined by a panel of clinicians, taking into account performance on the 
neuropsychological battery (test scores are compared to age, education, and race-specific 
norms), cognitive decline across study visits, and subject and informant interviews regarding 
cognitive functional status.  Based on these elements, all examined participants have a 
computer-algorithmic classification followed by expert-adjudicated review.  The computer 
algorithm, also developed by the expert panel for ARIC-NCS, has been used successfully to 
enhance uniformity in applying the diagnostic criteria.  In ARIC-NCS, the computer algorithm-
reviewer agreement was high:  99% for normal, 94% for MCI, and 95% for dementia, suggesting 
that the algorithm accords well with clinical judgment.  The informant interviews noted above are 
conducted with a knowledgeable informant at every exam where the participants meet a priori 
criteria for poor cognitive performance and who have significant cognitive decline from prior 
exams.  
7.7.1 Neurological interviews 
The neurologic interviews include the Clinical Dementia Rating Scale (CDR) and the 
Neuropsychiatric Inventory (NPI).  In addition, the Functional Activities Questionnaire (FAQ) is 
used in determining a participant’s level of daily functioning, but does not have a dedicated 
interview or form; rather, all FAQ items are embedded within the CDR interview.  Each of the 
measures are well-validated, standardized instruments that have been widely used in both 
clinical and epidemiologic studies of dementia. 
7.7.2 Clinical Dementia Rating Scale (CDR) 
The CDR gives important information about daily functioning, and is a required element in the 
determination as to whether an individual is demented or has MCI, or is normal.  The CDR 
includes the CDR Participant (CDP), and the CDR Informant (CDI), and the CDR Summary 
(CDS).   
The CDP (the portion of the CDR administered to the participant) is administered by a certified 
staff member.  The CDI is administered by a certified staff member with a knowledgeable 
informant.  After completion of these two components (and not in the presence of the subject or 
informant), a trained staff member will score the CDR (on the CDS form) based on the 
responses to the questions on both the CDP and CDI.  The CDR scores range from 0 (normal) 
to 3 (severe impairment) for each of the following 6 areas:  memory, orientation, judgment and 
problem solving, community affairs, home and hobbies, and personal care.  
7.7.3 Functional Assessment Questionnaire (FAQ) 
The FAQ score is embedded within the CDR.  Scores range from 0 (normal function), 1 (has 
difficulty, but does by self), 2 (requires assistance), to 3 (dependent).  There are 9 items from 
the CDR which are also FAQ questions (there are 10 FAQ questions; one CDR question 
encompasses two FAQ questions).  
7.7.4 Neuropsychiatric Inventory (NPI) 
The NPI consists of questions relating to personality and behavioral changes commonly seen in 
dementia.  This scale is completed with a knowledgeable informant after the CDI.  
 

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24 
7.8 
Neurocognitive battery 
This study will utilize the neurocognitive battery (described below) that was previously 
administered in ARIC-NCS32 and the parent ACHIEVE trial.  Four cognitive domains are derived 
from factor scores.33  These domains include:  
• 
Global function 
• 
Memory 
• 
Executive function 
• 
Language 
7.8.1 Ensuring speech understanding test  
Prior to performing the neurocognitive assessment, a brief test will be conducted to determine 
whether or not the participant can adequately hear the examiner.  In this test, five sentences are 
read aloud to the participant by the psychometrist, and the participant is asked to repeat back 
the sentence.  Participants are scored on the number of target words repeated back correctly (3 
target words/sentence).  Steps on how to proceed with neurocognitive testing if audibility is not 
established are outlined in the Manual of Procedures.  The parent ACHIEVE Steering 
Committee developed this protocol to guard against poor speech understanding from hearing 
loss directly confounding administration of neurocognitive tests with auditory stimuli.  
7.8.2 Mini-Mental State Exam (MMSE) 
The MMSE was developed as a brief, standardized instrument for screening a limited number of 
cognitive functions.34  The MMSE is administered by interview. 
7.8.3 Delayed word recall test (DWRT) 
The DWRT is a measure of verbal memory that requires the participant to recall a list of 10 
common nouns following a short delay.  The participant is presented with a stimulus card for 
each of 10 words.  The examiner reads each word aloud, and asks the participant to repeat the 
word and use it in a sentence.  This procedure is repeated, providing two exposures to the 
words.  Following an approximate 5-minute delay, during which the (non-verbal) digit symbol 
substitution test (DSST) is given, the participant is asked to recall as many words as possible.  
Scores range from 0 to 10 words recalled. 
7.8.4 Digit Symbol Substitution test (DSST) 
The DSST is a measure of psychomotor speed and sustained attention.  Besides its own value, 
the DSST also serves as a nonverbal distracter task, interposed between learning and recall for 
the DWRT above.  The participant is asked to translate numbers (1-9) to symbols using a key 
provided at the top of the test form.  The participant is provided with a pencil (without an eraser).  
Instructions are provided in a deliberate and slow pace.  One point is given for each correctly 
drawn symbol completed within the 90-second time limit.  Scores range from 0-93. 
7.8.5 Incidental learning 
The Incidental Learning Test was adapted from the WAIS-R NI and provides a non-verbal 
measure of recent memory.  Following the DSST, the participant is presented with the Incidental 
Learning Template.  The participant is asked to write down as many of the DSST symbols as 
he/she can remember, in any order.  Next, the participant is asked to write down the number 
that was paired with each of the symbols from the DSST.  Two scores are yielded:  1) Free 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
25 
Recall:  total number of symbols recalled, regardless of pairing, and 2) Pairing:  number of 
correct symbols correctly paired with corresponding numbers.  Scores for each range from 0-9. 
7.8.6 Trail Making Test Part A (TMT A) 
The TMT A is a timed task in which participants connect numbers in sequence as quickly as 
possible.  TMT measures attention, sequencing, mental flexibility, and visual search and motor 
function.  In TMT A, the participant is asked to draw a line and connect a series of numbers 
(from 1-25) as quickly as possible.  Prior to the test part, the participant is given a sample test to 
demonstrate the task.  The score for TMT A is the number of seconds required to complete the 
task.  A maximum of 240 seconds (4 minutes) and 5 errors is allowed. 
7.8.7 Trail Making Test Part B (TMT B) 
The TMT Part B is a timed task in which participants connect letters and numbers in sequence 
as quickly as possible.  TMT measures attention, sequencing, mental flexibility, and visual 
search and motor function.  In TMT B, the participant is asked to draw a line and connect a 
series of numbers and letters, alternating between a given number and letter (e.g., 1 to A, A to 
2, 2 to B, B to 3, etc.) as quickly as possible.  Prior to the test part, the participant is given a 
sample test to demonstrate the task.  The score for TMT B is the number of seconds required to 
complete the task.  A maximum of 240 seconds (4 minutes) and 5 errors is allowed. 
7.8.8 Logical Memory I and II 
This test, part of the Wechsler Memory Scale-Revised version, provides a measure of 
immediate and delayed verbal recall for the number of ideas presented in two stories, which are 
read to the participant.  Two stories are read to the participant, each at a slow and deliberate 
pace.  After each story is presented, the participant is asked to recall as much of the story as 
possible.  The Logical Memory I score provides a measure of immediate recall and is calculated 
as the average number of ideas recalled from Story A and B.  Each story contains 25 scoring 
units, the maximum score is 25 (25+25/2).  
An approximate 20-minute delay follows, during which the remaining (non-memory) tests are 
administered.  Following the delay period, the participant is again asked to recall the stories.  
The Logical Memory II score provides a measure of delayed recall and is calculated as the 
average number of story elements recalled from Story A and B.  As each story contains 25 
scoring units, the maximum score is 25 (25+25/2). 
7.8.9 Digit Span Backwards 
Digit Span Backwards is part of the Wechsler Memory Scale-Revised and provides a measure 
of attention and working memory.  The participant is read a series of numbers progressively 
increasing in length from two to eight digits.  After the numbers are read, the participant is asked 
to repeat the numbers in the reverse order.  Two trials at each digit length are performed (i.e., 2 
trials with 2 digits, 2 trials with 3 digits, etc.).  The test is discontinued after two consecutive 
errors of the same length item.  Scores range from 0-12. 
7.8.10 Boston Naming test 
The Boston Naming Test assesses visual naming ability using black-and-white drawings of 
common objects.  For this study, the 30-item version used by the National Alzheimer's 
Coordinating Centers Uniform Data Set will be used.  The participant is presented with a series 
of line drawings of objects and asked to name each object.  The items become progressively 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
26 
more difficult based on their frequency of occurrence in the English language.  A total score is 
calculated as the number of spontaneously produced correct responses.  Scores may range 
from 0-30. 
7.8.11 Word Fluency 
The Word Fluency Test is a measure of verbal functioning.  In this task, the participant is asked 
to produce as many words as possible that begin with the letters ‘F’, ‘A’, and ‘S’ within a time 
limit of 60 seconds for each letter, avoiding proper nouns, variations, plurals, and repetitions.  
The score is the total number of admissible words produced across letters. 
7.8.12  Animal Naming 
Animal Naming is a measure of category fluency (semantic association).  Category fluency, and 
specifically animal naming, is part of the Boston Diagnostic Aphasia Examination, the Stanford-
Binet test, and the CERAD.  The participant is asked to name as many different animals as 
possible within a 60-second time limit.  The score is given as the sum of all admissible names. 
7.8.13 Telephone neurocognitive assessment 
In the event that a participant is unable to be scheduled for an in-person visit (at the field site or 
at home) to complete the neurocognitive battery, a version of the neurocognitive battery 
modified for telephone administration may instead be administered.  The content of the 
Ensuring Speech Understanding test, the Digit Span Backwards test, and Animal Naming test 
remains the same as described above but with some modifications to instructions for telephone 
administration.  The content of the CDP (see section 7.7.2) remains the same, but the order of 
administration has been modified for use over the telephone.  The Word Fluency test has been 
shortened to collect on 'F' and 'A' words only, with 'S' words dropped. 
In lieu of the visual DWRT, an oral 10-item word list memory measure (CERAD, The 
Consortium to Establish a Registry for Alzheimer's Disease)45 test is used.  A shortened version 
of the MMSE, with two items modified for phone administration, and 19 original items dropped is 
used in place of the full MMSE.   
Oral versions of Trails A, where the participant is asked to count from 1 to 25 as quickly as they 
can, and Trails B, where the participant is asked to alternate between letters and numbers as 
quickly as they can until they reach the number 13, are used.  For each of the Oral Trails tasks, 
up to 5 attempts are allowed, with the maximum time permitted to complete each task being 4 
minutes.  The total time the participant took to complete the series, the total number correct, and 
the total number of errors are recorded.  
 
7.9 
Characterization of participants who leave the study early 
A final interview will be attempted with all participants who are either unable (e.g., due to illness) 
or unwilling to complete the study.  Trained interviewers will collect information by telephone or 
HIPAA-compliant video call regarding the reason for withdrawal and offer to schedule a home 
visit/telephone/video call for an abbreviated final study session.  In the absence such a session, 
because dropouts may be more likely to have dementia, we will attempt to ascertain dementia 
status using a telephone-based/video call-based assessment with the participant or informant 
interview conducted with a knowledgeable informant.  

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27 
In the case where the participant is alive and able to communicate by phone/video call, we will 
administer the Six Item Screener (SIS).  The SIS is a short instrument developed to identify 
cognitive impairment in older adults.  In the case where the participant has died or is otherwise 
unable to communicate by phone/video call, dementia status will be characterized by informant 
interview via telephone/video call using the AD8--a brief instrument, derived from the Clinical 
Dementia Rating Scale, developed to discriminate between normal aging and dementia.  
Notably, these procedures parallel ARIC’s ongoing dementia surveillance methods.  For ARIC 
participants, additional sources of information may also be used to complete ascertainment of 
dementia cases (e.g., discharge codes from hospitalizations, CMS, and ICD codes on death 
certificates). 
 
8 
Randomization 
Participants will be randomized in a 1:1 ratio to the telehealth HHC vs. conventional HHC 
delivery groups.  Randomization will be carried out using random blocks of sizes 2, 4, and 8, 
and will be stratified by degree of hearing loss (mild vs. moderate or greater), cohort (originally 
recruited from the ARIC Study or de novo from the community), and field center to achieve 
balance among these factors between HHC arms. 
 
ACHIEVE enrolled some spouses/cohabitating partners who were randomized together.  
Spouses or cohabitating partners in this follow-up study will also be randomized together.  They 
will be randomized as a unit with, arbitrarily, the first spouse/partner of the pair to be selected 
according to the random assignment procedure and the second spouse/partner of the pair 
receiving the same assignment.  Spouse/partner pairs will be randomized in spouse/partner-pair 
specific permuted order blocks of varying sizes within strata defined by participant status (at 
least one spouse/partner pair in ARIC or both non-ARIC participants) and by field site.  
 
Randomization will be performed after the baseline data for this follow-up study have been 
collected. 
 
8.1 
Measures to minimize bias 
Although the ACHIEVE HHC interventions are by nature unmasked, in order to minimize bias 
based on review of accumulating data by the project team, the ACHIEVE PIs, co-investigators, 
and key project staff (except one unblinded statistician) will remain blinded to accumulating 
data.  Additionally, study participants will be blinded to study hypotheses. 
 
This study design that incorporates the GrandPad for all participants minimizes potential bias 
(i.e., all participants receive a GrandPad, reducing the possibility that better outcomes with the 
telehealth HHC intervention are only due to those participants having access to a GrandPad) 
and allows for a direct efficacy study of whether telehealth HHC can improve outcomes when 
barriers to telehealth technology are effectively reduced. 
 

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28 
9 
Interventions 
9.1 
All participants 
At the ACHIEVE trial year 3 visit, which will serve as the ACHIEVE-HIFU baseline visit, all 
participants will complete the hearing intervention check-up (see 7.2.1 above), and the 
audiologist will address any hearing aid maintenance or repairs, as needed. 
 
At the ACHIEVE-HIFU randomization visit, after providing informed consent, participants will be 
randomized to receive either continued conventional clinic-based HHC or telehealth HHC 
delivery in addition to clinic-based care.  All participants will complete the Telehealth 
Acceptance Pre-Intervention questionnaire before they will be given a GrandPad tablet with 
general instructions on how to set it up, an overview of its basic functionality, and how to access 
manufacturer support services.  Prior to being informed of their randomized group, all 
participants will meet with the audiologist to complete COSI goal setting and complete the 
hearing intervention check-up (HICF).  Participants will then be informed of their randomization 
assignments. 
 
Participants randomized to the telehealth HHC delivery group will receive their first telehealth 
session at the end of the randomization visit, and they will continue to receive telehealth HHC 
for both years of the study, with clinic-based care occurring every 6 months.  Participants 
randomized to the conventional clinic-based HHC delivery group will receive conventional clinic-
based HHC for the first year of the study, receive their first telehealth session at the end of the 
Year 1 visit, and receive telehealth HHC for the second year of the study.  The telehealth and 
conventional HHC delivery models are described next. 
9.2 
Telehealth hearing health care 
We designed a hearing health care (HHC) service delivery model that leverages telehealth in 
order to provide more accessible long-term support of older adults using hearing aids.  The 
telehealth HHC service delivery model allows for remote access to HHC services and 
continuous support of participants’ hearing loss needs via telehealth to complement clinic-based 
hearing booster sessions that occur every 6 months.  The telehealth HHC intervention includes 
three telehealth delivery intervention sessions, as well as periodic asynchronous self-
management suggestions, and opportunities for ongoing remote support through both 
synchronous and asynchronous communications as needed. 
9.2.1 Telehealth Session A 
The first intervention session will occur in person.  For participants randomized to the telehealth 
HHC group, the first intervention session will occur at the end of the randomization visit.  The 
first telehealth session will consist of:  
1. Participant instruction in use of the GrandPad for telehealth sessions 
2. Re-introduction of the Hearing Loss Toolkit for Self-Management and C2Hear reusable 
learning objectives (RLOs) within the context of the telehealth platform 
3. Individual hearing and communication needs assessment, including review of technical 
intervention, optimizing the hearing intervention for telehealth sessions, and discussion 
of how telehealth can be used to achieve COSI goals 

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29 
9.2.2 Telehealth Sessions B and C 
Two follow-up intervention sessions (at approximately 3 weeks and 6 weeks post-
randomization) will occur via GrandPad video call (or telephone if the participant does not 
choose to use the GrandPad).  These sessions will primarily be individualized counseling 
sessions and will consist of: 
1. HIFU Intervention Check-Up components that can be collected remotely (i.e., hearing 
aid use, HAT use) 
2. Assessment of COSI goals achievement 
3. Discuss participants’ comfort with the telehealth platform 
9.2.3 Asynchronous provider-to-participant telehealth communications 
Clinician-initiated self-management suggestions related to the participant’s communication 
goals will be sent asynchronously via the email/text function on the GrandPad approximately 1-2 
times per month or communicated via telephone or other modalities if the participant does not 
use the GrandPad.  These asynchronized contacts could include reminders about:  
1. Reviewing the Hearing Loss Toolkit for Self-Management exercises related to their set 
COSI goals 
2. C2Hear RLOs  
3. Support of any device cleaning and hearing aid troubleshooting 
4. Hearing assistive technology (HAT) use 
 
These asynchronous contacts can lead to synchronous telehealth encounters or even an in-
clinic visit if determined to be necessary by the audiologist or requested by the participant.  As in 
the parent ACHIEVE study, participants will be able to reach out to the audiologist to initiate an 
interim visit/encounter to address any unanticipated needs if they arise, with a shift to telehealth 
visits as the first option for participants receiving the telehealth HHC delivery model. 
9.3 
Conventional clinic-based hearing health care 
Our research team previously developed the clinic-based, best-practices hearing intervention 
approach46 that is currently being implemented in the parent ACHIEVE trial based on the World 
Health Organization’s International Classification of Functioning, Disability and Health (WHO 
ICF)47 biopsychosocial framework.  In line with the WHO ICF framework, the main goal of 
intervention is improving a person’s quality of life by eliminating or minimizing limitations in 
activity and social participation.  The parent ACHIEVE hearing intervention begins with a 
comprehensive audiological assessment, followed by goal setting and provision of hearing aids 
and compatible hearing assistive technologies (HATs).  Counseling and education aimed at 
supporting hearing loss self-management skills are an integral component of the ACHIEVE 
hearing intervention, and are provided based on individual participant-prioritized goals.  
 
Participants randomized to the conventional, clinic-based hearing health care (HHC) arm will 
continue to be seen in-clinic semi-annually to reinforce hearing loss self-management strategies 
and perform hearing aid checks.  Following the COSI goal setting and HIFU hearing intervention 
check-up that all participants will complete during the randomization visit, participants 
randomized to the conventional, clinic-based HHC arm will be informed of their randomization 
assignment and reminded about how to continue accessing the conventional HHC supports that 
they received in the parent ACHIEVE study during the first year of the ACHIEVE-HIFU study 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
30 
(i.e., participants will be able to reach out to the audiologist to initiate an interim visit/encounter 
to address any unanticipated needs if they arise). 
 
9.3.1 Crossover to telehealth HHC delivery model 
After 12 months, participants assigned to the conventional HHC delivery model will crossover 
and receive the telehealth HHC delivery model for year 2 of this study.  At the end of the 1-year 
post-randomization visit, participants will receive telehealth session A (see section 9.2.1), 
followed by telehealth sessions B and C at approximately 3 and 6 weeks later, respectively, as 
described above. 
 
Full details of the interventions can be found in the Manual of Procedures. 
 
10 
Safety monitoring 
ACHIEVE-HIFU will follow safety procedures established as part of the parent studies 
(ACHIEVE and ARIC). 
 
10.1 
Data and safety monitoring board 
An independent Data and Safety Monitoring Board (DSMB) has been constituted in 
collaboration with the NIA for the parent ACHIEVE study and provides oversight at convened 
biannual meetings where interim unblinded and blinded data reports are reviewed.  An 
approved Data and Safety Monitoring Plan (DSMP) and DSMB charter guides data and safety 
monitoring for the ACHIEVE study.  The DSMB members comprise clinicians/investigators with 
expertise in clinical trials, neuropsychology, dementia, biostatistics, audiology, and 
otolaryngology.  This follow-up study to ACHIEVE will fall under the purview of the existing 
DSMB, and we will continue to follow all prevailing procedures as detailed in our approved 
DSMB charter and DSMP during the period of temporal overlap between ACHIEVE-HIFU and 
the parent ACHIEVE trial.  After the completion of the parent trial, we will determine, in 
consultation with the DSMB, NIA, and NIDCD, whether continued DSMB oversight of this 
telehealth trial is needed given the minimal risk nature of this study and based on the 
experience to date with the parent trial.  Because the primary outcome of this proposed study is 
hearing aid use at 1 year and the study interventions are minimal risk, there are no pre-planned 
interim data analyses to look for efficacy or futility that would lead to early stopping of this 
proposed trial. 
 
10.2 
Adverse events 
This follow-up study to ACHIEVE will use the procedures established in the parent ACHIEVE 
study for adverse events. 
 
Study participation and exposure to the HHC interventions is expected to have a low risk of 
adverse events for the participant.  At the same time, the age of the participants may naturally 
lead to numerous deleterious health outcomes.  In order to efficiently collect safety information 
that is relevant to study participation, interventions, and procedures, detailed information 

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31 
concerning a pre-specified set of adverse events and serious adverse events will be collected 
and evaluated throughout the conduct of the trial.  
 
An adverse event (AE) is an untoward medical occurrence, whether or not considered study-
related, which occurs during the conduct of a clinical trial. 
 
A serious AE (SAE) is any AE that results in any of the following outcomes: 
• Death 
• Life-threatening  
• Inpatient hospitalization or prolongation of existing hospitalization  
• Results in persistent or significant disability or incapacity 
• A major congenital anomaly or birth defect  
• Important medical event that may not result in one of the above outcomes, but may 
jeopardize the health of the study participant or require medical or surgical intervention to 
prevent one of the outcomes listed above.  
 
For this study, only the following adverse events and serious adverse events will be 
recorded and reported: 
Adverse Events 
Serious Adverse Events 
• 
Otitis externa 
• 
Death from any cause 
• 
Cerumen impaction or ear foreign body 
requiring removal by a physician 
 
 
An adverse event of otitis externa is defined as inflammation or infection of the ear canal 
resulting in pain, swelling, irritation, itching, or other related symptoms as diagnosed by the 
study audiologist or a physician.  Adverse event severity is defined as: 
• 
Mild if the symptoms are self-limited and resolve with interventions such as transiently 
limiting hearing aid use and/or the use of over-the-counter pharmacological therapies 
such as hydrocortisone cream or swimmer’s ear drops.  
• 
Moderate if the symptoms require evaluation and management by a physician and the 
use of topical prescription pharmacological therapies such as antibiotic ear drops.  
• 
Severe if the symptoms require evaluation and management by a physician and the use 
of oral or parenteral antibiotics.  
 
An adverse event of a cerumen impaction or ear foreign body requiring removal by a physician 
is defined as a cerumen impaction and/or ear foreign body that cannot be routinely managed by 
the study audiologist and requires evaluation and management by a physician (typically an 
otolaryngologist).  Adverse event severity is defined as:  
• 
Mild if the cerumen impaction or foreign body is resolved without further need for 
therapy besides over-the-counter pharmacological therapies such as cerumenlytic 
drops. 
• 
Moderate if there is an associated otitis externa requiring the use of topical prescription 
pharmacological therapies such as antibiotic ear drops.  

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
32 
• 
Severe if the cerumen impaction or ear foreign body results in a perforation of the 
tympanic membrane or an associated otitis externa requiring the use of oral or 
parenteral antibiotics.  
 
AEs or SAEs will be defined as unexpected or expected based on the judgement of the field 
site PI in consultation with the field site audiologist and/or study PIs Lin (who is a board-certified 
otolaryngologist) and Sanchez (who is a licensed audiologist) based on the following definitions:  
• 
Unexpected:  nature, severity, or frequency of the event is not consistent with 
information about the condition under study or intervention in the protocol and consent 
form 
• 
Expected:  event is known to be associated with the intervention or condition under 
study.   
 
Study-relatedness of AEs or SAEs will be based on the judgement of the field site PI in 
consultation with the field study audiologist and/or study PIs Lin/Sanchez based on the following 
guidelines:  
• 
Definitely Related:  The adverse event is clearly related to the investigational 
intervention – i.e., an event that follows a reasonable temporal sequence from 
administration of the study intervention, follows a known or expected response pattern to 
the suspected intervention, that is confirmed by improvement on stopping and 
reappearance of the event on repeated exposure and that could not be reasonably 
explained by the known characteristics of the subject’s clinical state. 
• 
Possibly Related:  An adverse event that follows a reasonable temporal sequence from 
administration of the study intervention follows a known or expected response pattern to 
the suspected intervention, but that could readily have been produced by a number of 
other factors. 
• 
Not Related:  The adverse event is clearly not related to the investigational 
agent/procedure - i.e., another cause of the event is most plausible; and/or a clinically 
plausible temporal sequence is inconsistent with the onset of the event and the study 
intervention and/or a causal relationship is considered biologically implausible.  
 
Unanticipated Problems 
An unanticipated problem is defined as an incident, experience, or outcome that meets all of the 
following criteria: 
• 
Unexpected – in terms of nature, severity, or frequency given the procedures and 
interventions used in the study as described in the protocol and informed consent given 
the characteristics of the study population 
• 
Possibly or definitely related to participation in the study 
• 
Suggests that the research placed the participant or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously known 
or recognized 
 
Some but not all adverse events may qualify as unanticipated problems.  
 
The Coordinating Center will review all recorded treatment-emergent adverse events and all 
serious adverse events (SAEs) from this pre-specified list and will provide a report to the 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
33 
Steering Committee and for submission to the IRB.  An SAE that is unexpected and possibly 
or definitely related to study participation or study intervention will be reported within 48 
hours by the sites to the PI and study project manager who will be responsible for reporting to 
the sIRB and the NIDCD. 
 
Adverse events and serious adverse events will be recorded on the electronic Adverse Events 
Form per study instructions.  Additionally, for unexpected and possibly or definitely related 
serious adverse events only, sites will record a narrative description of the serious adverse 
event, including any relevant test results and dates.  
 
All completed AE forms will be forwarded promptly to the Coordinating Center where they will be 
reviewed for completeness by the Coordinating Center staff and MPI Lin (who is a board-
certified otolaryngologist) and/or MPI Sanchez (who is a licensed audiologist).  In particular, the 
Principal Investigators will assure that documentation of each event is adequate to permit 
accurate inferences regarding causation (e.g., temporal associations, onset, course, response 
to patient or physician intervention, alternative etiologies) and severity.  Full details of 
procedures for reporting adverse events can be found in the Manual of Procedures. 
 
11 
Statistical considerations 
11.1 
Sample size 
This study is predicated on an already established cohort with a fixed sample size from the 
original ACHIEVE trial (N=490 for the clinic-based hearing intervention cohort).  In order to 
estimate the minimal difference in hours of continued hearing aid use that could be detected 
between the telehealth and conventional HHC groups after 12 months, we’ve made 
conservative assumptions based on expected loss to follow-up over time that would diminish the 
sample size and any observable outcomes.  The initial cohort receiving the hearing intervention 
was N=490.  Assuming conservatively that 5% of participants per year in this cohort are lost to 
follow-up or death, we would have a potential cohort of N=420 participants who would be 
eligible to participate after 3 years of follow-up from 2021-2022.  If we further assume that up to 
5% of these participants may then decline additional follow-up, we conservatively estimate that 
N=400 participants currently in the hearing intervention group will be recruited into this follow-up 
study (ACHIEVE-HIFU).  Further conservatively assuming:  1) 10-20% loss to follow-up in the 
12-month follow-up data collection; 2) 80% power and a 5% Type 1 error rate; and 3) that 
patterns of hearing aid utilization will be similar to those observed in the ACHIEVE pilot study, 
we would have the ability to detect an average treatment effect of 0.8 to 0.9 hours of hearing aid 
use between the telehealth HHC and conventional HHC arms.  
 
11.2 
Analytic approach 
The final statistical analysis plan was finalized in discussions between the study investigators 
and coordinating center. 
 
The comparison for all primary analyses is randomization to the telehealth HHC vs. 
conventional clinic-based HHC delivery model under the intention-to-treat paradigm, analyzing 
individuals according to their random allocation, irrespective of the treatment received.  

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
34 
Consistent with best practices in clinical trials, we will assess the comparability of the 
randomized groups with respect to known confounders, such as recruitment source, site, level 
of hearing impairment, Quick Speech in Noise score, self-reported acceptance of telehealth at 
baseline, self-reported and objectively measured baseline hours of hearing aid use, self-
reported baseline hours of hearing assistive technologies use, the number of days hearing log 
data was measured prior to randomization, and the number of visits prior to randomization at 
which a participant provided hearing logging data.48  These variables will be considered as 
covariates in all models.  If there is an imbalance between randomized treatment assignment, 
we may adjust for relevant confounders as well as explore the use of a prespecified inverse 
probability of treatment weight or a precise, locally efficient, augmented, simple estimator.49,50  A 
logistic regression model will be used to model the probability of attrition according to the 
confounders described above plus age, sex, and applicable interactions.  Inverse probability of 
attrition weights will be calculated and either included in the model for the primary outcome 
directly or cross-multiplied with inverse probability of treatment weights.  
We will use a weighted regression model with an identity link to compare average daily hours of 
hearing aid use at 1-year post-randomization between participants assigned to the telehealth 
HHC or conventional HHC.  To account for the non-normal distribution of the outcome, 
confidence intervals and p-values will be obtained using the bias corrected and accelerated 
bootstrap resampling procedure with 10,000 replicates. 
 
For continuous secondary outcomes, groups will be compared for differences at the 1-year 
follow-up using the same analytic approach specified for the primary outcome.  For binary 
secondary outcomes, either logistic regression or Poisson regression with robust error variance 
will be employed, depending on whether the outcome is rare or common.  For categorical 
outcomes, either ordinal or multinomial logistic regression models will be utilized, depending on 
the nature of the measure and empirical tests of the proportional odds assumption. 
 
Statistical significance for the primary outcome will be defined as p < 0.05.  Secondary 
outcomes will be evaluated for statistical significance with a Hochberg modification to the 
Bonferroni adjustment, in which the p-values of the five outcomes will be ordered.  The largest 
p-value will be compared relative to p < 0.05, and if met, all parameters will be considered 
significant.  If not, then the second largest p-value will be assessed relative to p < 0.05/2 = 
0.025, and if met, then it and all other parameters will be considered significant, and so on for 
the third p-value at p < 0.05/3 = 0.017. 
 
12 
Data management 
Trained data management and study management staff at the UNC CSCC will be responsible 
for coordinating data management.  The Coordinating Center (CC) uses a customized state-of-
the-art web-based data management system using Carolina Data Acquisition and Reporting 
Tool (CDART) which is also used for the parent ACHIEVE study and ARIC-NCS.  A complete 
description of all data management procedures has previously been developed for the parent 
ACHIEVE trial and has been approved by the ACHIEVE DSMB.  CDART uses a flexible, secure 
authentication system requiring a username and password.  In accordance with HIPAA, all 
individually identifiable information is encrypted and decrypted for local on-screen display at 
field sites.  The GrandPad tablet is HIPAA-compliant with respect to any telehealth sessions that 
occur using this platform. 

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35 
 
Data collection 
The CC has previously led the translation of the protocol data collection specifications into a 
consolidated set of clear, unambiguous electronic case report forms (eCRFs) for the parent 
ACHIEVE trial.  Each eCRF has a corresponding paper form to be used by sites in cases where 
data cannot be entered at the time of collection. 
 
Randomization and blinding  
Randomization will be implemented within CDART.  Although the ACHIEVE hearing 
interventions are by nature unmasked, in order to minimize bias based on review of 
accumulating data by the project team, the ACHIEVE PIs, co-investigators, and key project staff 
(except one unblinded statistician) will remain blinded to accumulating data.  In all cases, hours 
of hearing aid use (primary outcome), a completely objective data point, will be gathered directly 
from hearing aid data logging software, and source data will be verified as part of the quality 
assurance procedures.  All other non-audiological secondary outcomes will be collected by 
trained technicians, rather than the site audiologist. 
 
Data quality control and monitoring 
Quality and completeness of recorded data will be assured on an ongoing basis by range and 
logic checks upon entry, queries for missing or inconsistent data, and periodic monitoring.  
Consistent with the parent ACHIEVE trial a Quality Control Subcommittee chaired by MPI Lin 
meets monthly to review all data collection procedures and summary data tables to ensure the 
integrity of data collection and to troubleshoot as needed. 
 
Records retention 
MPIs and field center PIs will retain study essential documents and specimens for up to 10 
years following study completion. 
 
Ethical considerations 
This study is 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. 
 
This protocol and any amendments will be submitted to a properly constituted single Institutional 
Review Board (sIRB), in agreement with local legal prescriptions, for formal approval of the 
study conduct.  The decision of the sIRB concerning the conduct of the study will be made in 
writing to the investigator and a copy of this decision will be provided to the sponsor before 
commencement of this study. 
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study.  This consent form will be submitted with the protocol for review and approval by the sIRB 
for the study.  The formal consent of a subject, using the IRB-approved consent form, will be 
obtained before that subject undergoes any study procedure.  The subject will sign the consent 
form, as will the investigator-designated research professional obtaining the consents. 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
36 
13 
Study sites and structure of the study team 
13.1 
Field centers 
The field centers where the research will be conducted are the same as the parent ACHIEVE 
study.  The field centers will be responsible for recruiting participants into the new study, 
administering the HHC intervention, and collecting follow-up outcome data. 
• 
Washington County, Maryland (Johns Hopkins center located in Hagerstown, MD) 
• 
Jackson, Mississippi (University of Mississippi Medical Center) 
• 
Forsyth County, North Carolina (Wake Forest University Health Sciences) 
• 
Minneapolis, Minnesota (University of Minnesota) 
13.2 
Coordinating Center (CC) 
The CC is located at the University of North Carolina (UNC).  UNC currently serves as the CC 
for the ACHIEVE trial and ACHIEVE-MRI study and has served as the CC for numerous other 
studies, including ARIC.  The CC will be responsible for programming data entry screens into 
the data management system, providing reports on study progress and data quality, creating 
datasets for sharing with investigators, and participating on study committees.  See section 12 
Data management for details on the data management system and data monitoring.  See 
section 10.2 Adverse events for details on reporting of adverse events and unanticipated 
problems. 
 
In addition to data management, the CC manages a centralized study-specific website, where 
study staff can login with their assigned individual user ID and password to access the latest 
version of the protocol, manuals of procedures, paper case report forms, current and prior IRB 
approval letters for each participating site, memos, and other relevant study documents.  The 
website also has a directory feature that maintains contact information for all investigators and 
study team members at each participating site.  The CC is responsible for distributing memos to 
the site PIs and/or study coordinators when there are changes to the protocol or clarifications to 
study procedures. 
13.3 
Hearing intervention unit 
The University of South Florida (USF) will be responsible for training and oversight of the fidelity 
of the hearing intervention.  USF will participate on study committees and lead the hearing 
intervention subcommittee.  
13.4 
Analysis and study governance site 
Johns Hopkins University (JHU) is the analysis and study governance site.  JHU will be 
responsible for overall trial coordination, leading several of the committees (described in the 
next section).  JHU will be responsible for preparing and maintaining the study protocol, 
consent, and other study documentation, and will work with the CC to have these study 
documents distributed and/or posted to the study website as needed.  JHU will also be 
responsible for preparing NIH progress reports. 
13.5 
Single IRB 
Johns Hopkins Medicine is serving as the single IRB for this study.  It is the preference of Johns 
Hopkins Medicine IRB to use the SMART IRB reliance agreement as the basis of reliance.  The 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
37 
SMART IRB master reliance agreement was created in 2016 to harmonize and streamline the 
IRB review process for multisite studies.  It enables reliance on a study-by-study basis, clearly 
defines roles and responsibilities of relying institutions and reviewing IRBs, and eliminates the 
need to sign reliance agreements for each study [e.g., a non-SMART IRB agreement].  900+ 
institutions have already signed onto this agreement and are actively using it as the basis of 
reliance for multisite projects.  Sites that will rely on JHM IRB are still responsible for conducting 
a local context review prior to the start of research at their site and for following any local and 
institutionally required policies as it applies to research at their site [e.g., reporting of 
unanticipated problems]. 
13.6 
Study organization 
Study organization will be based directly on the existing organizational framework used in the 
ongoing ACHIEVE trial consisting of an overarching Steering Committee that interfaces with the 
ARIC study, NIH, and DSMB (when applicable).  Under the Steering Committee, several 
additional committees (Operations, Quality Control, Neurocognitive Adjudication, Intervention 
Fidelity and Quality, and Publications) oversee day-to-day execution of the study. 
 
14 
History of protocol amendments 
Minor changes to page numbering and formatting and minor corrections and clarifications were 
made throughout the document.  Substantive changes are highlighted in the below table. 
Protocol 
version 
Affected section(s) Brief description of change Brief rationale for change 
v1.0 
(29-Jun-2021) 
Original version of the protocol approved by the sIRB. 
v1.1 
(20-Sep-2021) 
Version of the protocol approved at the time the first participant was randomized. 
5.1 Eligibility 
Vision impairment exclusion 
criteria changed from 20/40 
to 20/63 
This is a correction to match the 
criteria used in ACHIEVE 
7.1 Schedule of 
activities (Table 1); 
9.2 Telehealth 
hearing health care; 
9.3.1 Crossover to 
telehealth HHC 
delivery model 
Telehealth Sessions 
renamed from Session 1, 2, 
3 to Session A, B, C 
Sessions named with letters, rather 
than numbers, is consistent with 
how intervention sessions have 
been named previously in ACHIEVE 
7.1 Schedule of 
activities (Table 1) 
Visits renamed as follows: 
Yr 0.5 6-month 
Yr 1 Year 1 
Yr 1.5 18-month 
Yr 2  Year 2 
Consistency with visit names used 
in the database 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
38 
Protocol 
version 
Affected section(s) Brief description of change Brief rationale for change 
7.1 Schedule of 
activities (Table 1); 
9.1 Interventions – 
all participants; 
9.3 Conventional 
clinic-based hearing 
health care 
HIFU Intervention check-up 
added to Randomization Visit 
and noted as only required at 
Session A if not the same 
day as the visit 
HIFU Intervention check-up should 
be done on all participants at the 
start of HIFU; HIFU Intervention 
check-up should be repeated during 
Session A if Session A occurs on a 
separate day from 
Randomization/Year 1 Visit; 
otherwise, it should not be repeated 
7.1 Schedule of 
activities (Table 1); 
7.5.5 COVID impact 
questionnaire 
Added COVID impact 
questionnaire to semi-annual 
and annual visits 
This questionnaire, which was 
added during the ACHIEVE parent 
trial, and which we had planned to 
continue administering it in 
ACHIEVE-HIFU, had been 
inadvertently omitted from the 
protocol 
7.1 Schedule of 
activities (Table 1); 
7.5.6 Telehealth 
acceptance 
questionnaires 
“Telehealth acceptability” 
changed to “Telehealth 
acceptance” 
Correction 
7.1 Schedule of 
activities (Table 1); 
9.1 Interventions – 
all participants; 
9.2.1 Telehealth 
session A 
Telehealth acceptance 
questionnaires moved out of 
Session A to the 
Randomization/Year 1 Visit 
TAP should be collected on all 
participants at Randomization, and 
ideally, should be collected by a 
non-audiologist.  At the Year 1 Visit, 
a non-audiologist should administer 
the TAP or TAF, depending on 
whether the participant has received 
the telehealth intervention yet. 
7.1 Schedule of 
activities (Table 1); 
 
CDP, CDI, CDS, and NPI 
removed from semi-annual 
visits. 
This is a correction for consistency 
with what is currently being done in 
ACHIEVE. 
v1.2 
(20-Jan-2022) 
Cover page 
Clinicaltrials.gov identifier 
added. 
The Clinicaltrials.gov registration 
was completed prior to enrollment of 
participants, and the protocol is 
being updated to reflect the 
identifier. 
3 Study objectives 
and end points 
Details on how outcomes are 
assessed and scored, and 
interpretation of scores have 
been added. 
Descriptions of the outcomes were 
expanded to clarify the outcomes 
and make them consistent with the 
outcomes listed in the study’s 
clinicaltrials.gov record. 
6.1 Informed 
consent 
Added sub-section on re-
obtaining consent in the 
event of consent changes. 
The protocol did not previously 
address the process for re-consent 
due to consent changes.  Because 
the study involves telehealth 
(remote) visits, and not all contacts 
occur in person, flexibility has been 
added to allow re-consent to be 
provided verbally or via mail. 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
39 
Protocol 
version 
Affected section(s) Brief description of change Brief rationale for change 
6.2 Participant 
confidentiality 
Details on the results 
provided to participants and 
their private physicians were 
updated. 
These changes reflect corrections to 
the planned sharing of results to 
correspond with sharing of results in 
the parent ACHIEVE trial. 
7 Study 
assessments and 
procedures 
Removed the stipulation that 
the parent ACHIEVE trial 
Year 3 visit will serve as the 
baseline if completed within 
the 6 months preceding 
randomization in ACHIEVE-
HIFU. 
Decision by the ACHIEVE 
investigators to allow the Year 3 
ACHIEVE visit to serve as the 
baseline for ACHIEVE-HIFU, even if 
more than 6 months have passed, 
and to not conduct a repeat baseline 
visit.  This change allows additional 
scheduling flexibility and reduces 
potential participant burden. 
7.1 Schedule of 
activities (Table 1) 
COSI goals achievement 
removed from the Initial 
Conventional Randomized 
HHC arm’s Telehealth 
Session A. 
This removal is a correction – goals 
achievement will be assessed at the 
Year 1 visit, which will often occur 
the same day or within the week 
prior to Session A for the group 
randomized to conventional HHC, 
so goals achievement will not be 
repeated at Session A. 
12 Data 
management 
Removed text indicating that 
technicians will be blinded to 
randomization status. 
The primary outcome for ACHIEVE-
HIFU is objectively measured hours 
of hearing aid use, so technicians 
collecting other outcomes are not 
required to be blinded. 
14 History of 
protocol 
amendments 
New section added. 
The relevant summary of changes 
for the current protocol version will 
be outlined in the table at the 
beginning of the protocol, but the full 
history of protocol changes will be 
maintained within this newly added 
section in the protocol. 
 
 
 

ACHIEVE HIFU Protocol, v.1.3 June 5, 2024 
 
40 
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