Study design, participants, and setting
Our study is a randomized, controlled trial lasting 12 months with two parallel groups, the treatment group and the control group. According to the list provided by the Hearing Center of Linyi Disabled Persons’ Federation, 464 people are randomly selected. Participants are prescreened by telephone and complete a hearing screening at baseline (T0). Those in the treatment group are prescribed with hearing aids and receive a post intervention of reinstruction in use of hearing aids 6 months after T0. While the control group receive no interventions. The follow-up surveys are scheduled 12 months after T0 to trace changes in health outcomes (Fig. 1).
Eligibility Criteria
Eligibility criteria are designed to identify community-dwelling adults with hearing loss who may possibly benefit from hearing rehabilitation (Table 1).
To be included in the study, each person must meet the following inclusion criteria: Participants are adults aged 16 years and above with untreated bilateral hearing loss, and are required to wear a hearing aid by otologists. Participants are community-dwelling and will remain in the local area during the study period. They should be fluent Chinese speakers.
Exclusion criteria include inability to read or write, prior cognitive, mental, language or movement disability diagnosis, medical contraindication to hearing treatment (e.g., draining ear), untreatable conductive hearing loss (difference in air audiometry and bone audiometry (“air-bone gap”) > 15 dB in two or more contiguous frequencies in both ears that cannot be medically resolved), or unwillingness to regularly wear hearing aids.
Table 1
Inclusion and exclusion criteria
Criteria | Description |
Inclusion | Ÿ Age 16 years old and above; Ÿ Diagnosed with some degree of hearing loss and are required to wear a hearing aid; Ÿ Plans to stay in the geographic area for study duration; Ÿ Community-dwelling; Ÿ Fluent Chinese speaker. |
Exclusion | Ÿ Inability to read or write; Ÿ Cognitive, mental, language or movement disability diagnosis; Ÿ Self-reported use of a hearing aid in the past 1 year; Ÿ Unwilling to wear hearing aids on daily basis; Ÿ Medical contraindication to use of hearing aids (e.g., draining ear); Ÿ Conductive hearing loss with air-bone gap > 15 dB in two or more contiguous frequencies in both ears that cannot be resolved. |
Study Interventions
Participants in the hearing treatment group are prescribed with hearing aids at baseline, while the control group with no interventions. Reinstruction in use of hearing aids is prescribed during booster visits held 6 months and 12 months post-randomization. Unscheduled interim visits may also be sporadically required (e.g., hearing aid malfunction). Participants in the control group will not have access to hearing aids. They will be asked to attend twice for this project: baseline and follow-up 12 months later.
Modifications
Study participation and hearing intervention are expected to have a low risk of adverse events. But the age of the participants may naturally lead to certain deleterious health outcomes. In case of any accidental injury, lack of efficacy, or withdrawal of participant consent during the trial, investigators can modify or discontinue the trial with the approval of the principal investigator (PI).
Adherence
Adherence to the study intervention will be assessed at each study visit using questions designed to capture adherence in both the treatment and control groups. Strategies to promote adherence include:
• Individual assessment and instruction.
• Participants are asked to bring a communication partner with them to the study visits.
• Participants who miss a scheduled meeting are contacted by telephone by study staff to encourage continued participation and to evaluate and overcome barriers to participation.
For the treatment group, it additionally includes:
• Potential intervention benefits are structured given the participant’s level of hearing loss in order to ensure that participants’ expectations are reasonable and realistic.
• Participants are informed that they are allowed to keep the hearing aids for free if they complete all study visits.
Outcomes Measures
Primary outcome
The primary study outcome is the 12-month changes in quality of life from 2019 baseline to 2020 follow-up. Quality of life can be measured by standard tests of Short Form 12 Health Survey (SF-12) [31] and EuroQoL 5-Dimension (EQ-5D) [32].
Secondary outcomes
Key secondary outcomes include changes in sub-scores of SF-12 (physical and mental health) [31] and EQ-5D (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) [32]. Other secondary outcomes are health variables independently associated with hearing loss, including physical functioning (ADLs, IADLs) [33], chronic diseases, cognitive function (MMSE) [34], depressive symptoms (CES-D) [35], social support (LSNS) [36], hospitalizations, and falls; as well as the direct and indirect medical costs and loss of productivity in the study duration.
Hearing outcomes
Participants are required to receive pure tone audiometry at the thresholds of 0.5, 1, 2, 4 kHz to derive accurate hearing data. Besides pure tone audiometry, standardized questionnaires like Hearing Handicap Inventory for the Elderly—Screening version (HHIE-S) [37], combined with participants’ self-reported hearing status, will be gathered to supplement the objective hearing data. For participants randomized to the hearing intervention group, audiologic outcomes to verify the intervention effects, such as the International Outcome Inventory for Hearing Aids (IOI-HA) [38], are gathered semiannually post-randomization.
Covariates
Sociodemographic factors such as age, gender, residency, family information, socioeconomic status and other clinical factors are collected at baseline and the follow-up survey.
Sample Size
Power calculations showed that 404 (202 in each group) participants are required in each group to obtain 80% statistical power with a 5% significance level, and to detect a 0.28-SD difference in the mean change from baseline in quality of life score to 12-month follow-up [39]. To account for drop-in (uptake of hearing aids in the control group) and drop-out (discontinuation of hearing aid use in the treatment group), 464 persons are included, of which 232 are in the intervention group and 232 in the control group.
Recruitment
Our recruitment will last one month, beginning Summer 2019. Adults with untreated hearing loss will be recruited according to the list of people with hearing loss provided by the hearing center of Linyi Disabled Persons’ Federation. Informed, written consent is obtained from all participants prior to participation.
Randomization
Participants are randomized stratified by severity of hearing loss, so as to avoid uneven distribution of participants. A researcher who is not involved in data collection or analysis will use a random sequence generator (http://www.random.org) to allocate participants in a random sequence to the treatment or control group. In a separate room after completion of the baseline measurements, an independent researcher will tell participants to which group they have been allocated, thereby ensuring concealment of the identity and characteristics of participants.
Blinding
Neither study participants nor researchers collecting outcome data can feasibly be blinded to randomization status. Precautions to minimize potential bias resulting from the lack of blinding include: (1) blinding of participants to the study hypothesis; (2) use of standardized protocols for training of data collectors and assessment of study outcomes; (3) masking of field working staff to block size, to avoid unintentional and possibly unconscious bias by study staff during data collection.
Data Collection
Standardized data forms or tablets are used to collect data with paper back up available in case of tablet failure. Participants will fill in all questionnaires in a separate room. To ensure that appropriate help and guidance can be given when needed, one of the researchers will present. Meanwhile, communication partners who communicate with participants on a daily or near-daily basis (e.g., spouse) are often a key to getting accurate results. Therefore, accompanying adults are also invited to join the study and contribute to the data.
To minimize data-entry errors, the questionnaires have inbuilt check-and-skip rules. And the questionnaires were tested on four participants beforehand, who found the questions understandable and possible to complete in 30–45 minutes. For participants who withdraw from the trial, any data collected up to the withdrawal date will be retained and included in the analyses. Data are collected at the local field prior to randomization (baseline T0), after 6 months (post intervention T1) and 12 months after baseline (Follow-up T2). A SPIRIT flow diagram illustrates the data collection in the intervention group and control group (Table 2) [40].
Table 2
Schedule of enrollment, interventions and assessments
Timepoint | Study Period |
Enrollment -T1 -30 to -1 day | Allocation T0 day 0 | Post-allocation T1 6 months | Close-out T2 12 months |
T a | C b | T a | C b | T a | C b | T a | C b |
Enrollment | | | | | | | | |
Eligibility screen | × | × | | | | | | |
Informed consent | × | × | | | | | | |
Allocation | | | × | × | | | | |
Intervention | | | × | | × | | × | |
Assessments | | | | | | | | |
Socio-demographic data | × | × | × | × | | | × | × |
Hearing outcome | | | | | | | | |
Pure tone audiometry | | | × | × | | | × | × |
HHIE-S score | | | × | × | | | × | × |
Self-reported hearing | | | × | × | | | × | × |
IOI-HA score | | | | | × | | × | |
Quality of life (primary outcome) | | | | | | | | |
SF-12 score | | | × | × | | | × | × |
EQ-5D score | | | × | × | | | × | × |
Secondary outcomes | | | | | | | | |
Sub-dimension of SF-12 | | | × | × | | | × | × |
Sub-dimension of EQ-5D | | | × | × | | | × | × |
Physical functioning (ADLs) | | | × | × | | | × | × |
Physical functioning (IADLs) | | | × | × | | | × | × |
Chronic diseases | | | × | × | | | × | × |
Cognitive function (MMSE) | | | × | × | | | × | × |
Depression (CES-D) | | | × | × | | | × | × |
Social support (LSNS) | | | × | × | | | × | × |
Hospitalizations | | | × | × | | | × | × |
Falls | | | × | × | | | × | × |
Medical costs | | | × | × | | | × | × |
Loss of productivity | | | × | × | | | × | × |
Note: a T: treatment group; b C: control group |
Abbreviations: HHIE-S, Hearing Handicap for the Elderly-Screening Version; IOI-HA, The International Outcome Inventory for Hearing Aids; SF-12, Short Form 12 Health Survey; EQ-5D, EuroQoL 5-Dimension; ADLs, Activities of Daily Living; IADLS, Instrumental Activities of Daily Living; MMSE, Mini-Mental State Examination; CES-D, Center for Epidemiologic Studies-Depression; LSNS, Lubben Social Network Scale. |
Data Management
The data entry is double-checked for errors or omissions by an investigator blinded to the participants’ group allocation. For data coding, some measures such as range checks in data values are conducted. Then data shall be filed and stored in categories, and have multiple backups on different disks or recording media.
Statistical analysis
In the statistical analysis, intention-to-treat (ITT) principle is applied with conservative estimates of missing data [41]. Participants’ characteristics will be summarized using descriptive statistics (mean, standard deviation, frequency). Analysis of variance or t tests are performed to compare means; Mann-Whitney U tests are used to compare variables with non-normal distribution. Baseline data will be used to investigate the characteristics of participants who discontinue or deviate from the trial and/or intervention. The magnitude of changes over time across study groups will be examined by a multiple imputation analysis of covariance model, so as to evaluate the intervention effect.
In addition, some variables such as socioeconomic status and social support may potentially affect the utilization of hearing rehabilitative services, so the interaction between socioeconomic status or social support with the hearing intervention can be analyzed to gain further results. The cost-effectiveness analysis is based on the cost of the intervention, effects in improving health-related quality of life; decreasing inpatient and outpatient visits; saving healthcare costs and recovering productivity. By these means, we aim to explore the most cost-effective intervention strategy to improve the quality of life of the people with hearing loss.
Data Monitoring
The principal investigator (PI) is responsible for the quality and integrity of data collected. During the period of recruitment, interim analyses will be supplied in strict confidence, which may include analyses of data from other comparable trials. In the light of these interim analyses, the PI will advise if the intervention has been proved, or different from expected. Then the PI will decide whether or not to modify the trial. Unless this happens, however, study staff will remain ignorant of the interim results.
Adverse Events
In our study, adverse events will be collected and recorded after participants have provided consent and enrolled, until the end of the study. If a participant experiences an adverse event after the informed consent is signed (entry) but the participant has not started to receive study intervention, the event will be reported as not related to our intervention. An adverse event that meets the criteria for a serious adverse event (SAE) will be reported to the institutional review board (IRB). And study personnel will document the circumstances.
Auditing And Inspecting
PI will permit study-related monitoring, audits, and inspections by the IRB of all study related documents (e.g. source documents, regulatory documents, data collection instruments, study data etc.). PI will ensure the capability for inspections of applicable study-related facilities.
Patient And Public Involvement Statements
This trial is carried out without patient or public involvement. Neither patients nor the public are involved in the development of the objective, design or implementation of this trial. Patients will not be invited to develop patient-relevant outcomes or interpret the results, or to participate in the writing or editing of the final manuscript for readability or accuracy.
Ethics/dissemination
Ethics approval and protocol amendments
The study was approved by Peking University’s Institutional Review Board (IRB00001052-19046). Any modifications to the protocol which may impact on the study, or the potential benefit and safety of the participants, including changes of study objectives, study design, participants, sample sizes, study procedures, or significant administrative aspects will require a formal amendment to the protocol. Such amendment will be approved by the IRB prior to implementation.
Consent And Confidentiality
Investigators will introduce the trial to participants in light of the information provided in the information sheets. Participants will then be able to have an informed discussion with the investigator. Investigators will obtain written consent from willing participants. For confidentiality, each participant will be given a unique identification number. Other identification information such as names, mobile phone numbers and addresses will not be recorded in the same form as sensitive data. In case of any accidental injury during the trial, medical treatment and economic compensation will be provided according to the laws and regulations of China.
Dissemination
PI will be given access to the cleaned data sets. Results will be disseminated in the clinical and scientific communities and also to the population with hearing loss via peer-reviewed research publications both online and in print, conference and meeting presentations, posters, newsletter articles, website reports and social media. Results will be reported according to the Consolidated Standards of Reporting Trials (CONSORT) guidelines [42]. Important protocol modifications will be reported when findings are disseminated.