Pilot-testing a Multiplayer HIV and Sexually Transmitted Infection Prevention Video Game Intervention for Black Adolescent Girls: Protocol for a Randomized Controlled Trial

Background Black adolescent girls aged between 14 and 19 years are more likely than White girls to be diagnosed with a sexually transmitted infection (STI). As STI diagnosis is associated with an increase in the risk for HIV acquisition, an early intervention specifically tailored to Black adolescent girls is warranted. A web-based video game intervention has the potential to reach this demographic. Because studies of social and behavioral determinants of disease demonstrate the protective role of peer group structures on individual outcomes, a multiplayer game can facilitate opportunities to exchange and evaluate information, learn social norms, develop behavioral skills, and allow peers to influence attitudes and behavior. No prior research has examined the feasibility of a web-based multiplayer game intervention for this population. Objective This study describes the protocol for a randomized controlled trial (RCT) pilot-testing the feasibility, acceptability, and limited efficacy of a multiplayer game–based intervention for increasing HIV and STI testing and condom use in Black adolescent girls. Methods We enrolled 79 Black adolescent girls aged 14 to 19 years residing in the United States into a 2-arm parallel RCT. The intervention is a theory-based, community-informed, multiplayer game that can be played with peers on the web using videoconferencing software. The goal of the game is to empower Black adolescent girls to make healthy decisions regarding dating, relationships, and sex, thus reducing HIV and STI infection. Control condition participants received a list of resources after playing a time and attention control game. All study procedures were conducted via the internet. We conveniently sampled Black adolescent girls using web-based advertisements. Study assessments occurred at enrollment, 1 week, 1 month, and 4 months after enrollment. The primary outcome of this study is increased HIV and STI testing by Black adolescent girls. Secondary outcomes include increased condom use, self-efficacy to use condoms, positive attitudes toward condom use, intentions, harm perceptions, HIV and STI and pre-exposure prophylaxis knowledge, positive sexual norms, sexual communication with partners, and reduced incidence of sexual risk behaviors associated with HIV and STI transmission. Secondary outcomes also included assessment of intervention feasibility and acceptability. Results From February to April 2022, a total of 79 Black adolescent girls were enrolled, with 40 (51%) having been randomized into the intervention condition and 39 (49%) into the control condition. At baseline, participant ages ranged from 14 to 19 (mean 16.4, SD 1.23) years. Conclusions Web-accessible game interventions overcome common impediments of face-to-face interventions presenting a unique opportunity to reach Black adolescent girls and improve their sexual health and self-efficacy. Trial data will provide information about the limited efficacy of the intervention and inform future web-based studies and a larger RCT aimed at improving the sexual health of Black adolescent girls. Trial Registration ClinicalTrials.gov NCT04108988; https://clinicaltrials.gov/ct2/show/NCT04108988 International Registered Report Identifier (IRRID) DERR1-10.2196/43666

1 R21 HD098031-01 3 BSPH HIEFTJE, K to play. Results from this study suggest that One Night Stan is a feasible intervention approach and may be efficacious in helping players develop a pattern of cognitions and motivation that can protect them against the risk of HIV. Together, a team comprised of experts from the Yale Center for Health & Leaning Games will build upon this formative work and pilot data to adapt One Night Stan to a multiplayer videogame for younger target audience of Black adolescent girls. For this proposal, we will evaluate the feasibility and preliminary efficacy of One Night Stan at increasing self and partner HIV/STI testing by conducting a pilot randomized controlled trial with 80 young Black adolescent girls ages 14-18. We will also explore the efficacy of the intervention for increasing players' HIV/STI knowledge and for increasing intentions and attitudes around safer HIV/STI practices. As a multiplayer videogame, the intervention is a compelling framework for Black adolescent girls who constantly interact and are influenced by their peers.

PUBLIC HEALTH RELEVANCE:
This project is designed to develop and test a multiplayer videogame intervention for adolescent black girls ages 14-18. The goal of this proposal is to increase HIV/STI self and partner testing and reduce sexual risk behaviors such as non-condom use in order to decrease their risk for human immunodeficiency virus (HIV) and other sexually transmitted infections (STI). Because the game will be played with adolescent females and their peers, this project has the potential to spread beyond the individual to influence public health and decrease the number of new cases of HIV/STI.

CRITIQUE 1
Significance: 3 Investigator(s): 2 Innovation: 4 Approach: 5 Environment: 2 Overall Impact: The overall goal of this R21 application is to develop and pilot test a group-based game for Black adolescent girls (ages 14-18) who are sexually active. The scientific premise of the study is strong, as there is a need to curtail HIV disparities among this group. The team is wellequipped to carry out the proposed study, as they have prior expertise in eHealth gaming. Overall, the proposed intervention is innovative in its mode of delivery, yet the overall impact of the intervention is diminished by concerns regarding sample selection, empirical justification for migrating the card game into a videogame format, and issues regarding the pilot trial design.

Significance:
Strengths  Young women, particularly racial/ethnic minority women, remain a high priority population for HIV prevention.
 eHealth games can promote behavior change and have greater potential for scalability if found to be efficacious.

Weaknesses
 Unclear why team decided to make game playable only in person, as this approach counters the benefits of an online game delivery modality.  Limited justification for the transition from a card game (One Night Stan) into a game. There is no preliminary efficacy provided; furthermore, it seems the original game was built for an older population than the one being studied in this application.

Investigator(s):
Strengths  PI has expertise conducting e-health interventions for youth.  Co-I team is strong, with complementary expertise.

Innovation:
Strengths  The use of multiplayer gaming to deliver an intervention is innovative.
 Iterative revisions based on user-centered feedback is noteworthy.

Weaknesses
 The use of qualitative data to understand Black teenagers' risk behaviors is not innovative and has been explored thoroughly in the literature.

Approach:
Strengths  Sequential focus group feedback is a strength of the application as the team integrates feedback on the game design and logistics.
 Peer-to-peer feedback during game design is a strength of the approach.

Weaknesses
 It is unclear what the intervention components are, and how they align with developmental considerations.
 The team proposes a grounded theory approach in Phase 1, which seems inadequate for the proposed work and the study goals.  Why is partner testing a primary outcome of the study? What if a participant doesn't have a partner? Given the pilot nature of the study, I would focus solely on participants' behaviors (e.g., HIV/STI testing, sex risk).
 Since groups will be kept consistent after randomization, how do you know whether the game creates the expected intervention effect or if it's a result of group bonding? Further, it would seem like adjusting for the clustering effect may be needed.  Satisfaction/acceptability should be asked in both arms.
 Power estimates should include proposed effect sizes.

Environment:
Strengths  Yale has the necessary resources to support the proposed work.

 None Noted
Study Timeline: Strengths  Timeline provided seems feasible, with sufficient cushion to overcome any potential delays that may arise during the project start-up and programming phase.

Protections for Human Subjects:
Acceptable Risks and/or Adequate Protections  Team should consider how to circumvent potential contamination due to peer exchanges and intended/unintended disclosure by peers.
 Strongly encourage team to explore a waiver of parental consent to avoid unintended disclosure of sexual activity to family, and reduce selection bias during recruitment.

Data and Safety Monitoring Plan (Applicable for Clinical Trials Only):
Acceptable  DSMP is adequate and will be overseen by Yale

Inclusion of Women, Minorities and Children:
 Sex/Gender: Distribution justified scientifically  Race/Ethnicity: Distribution justified scientifically  For NIH-Defined Phase III trials, Plans for valid design and analysis: Not applicable  Inclusion/Exclusion of Children under 18: Including ages <18; justified scientifically  Black/AA young women (14-18 years) will be enrolled; justified.

Not Applicable (No Vertebrate Animals)
Biohazards:

Budget and Period of Support:
Recommend as Requested:

CRITIQUE 2
Significance: 2 Investigator(s): 2 Innovation: 2 Approach: 2 Environment: 1 Overall Impact: This is an innovated new R21 application that seeks to develop and test a multiplayer videogame intervention for black adolescent and young women (BAYW) using cellphones based on a prior developed multi-player card game "One Night Stan". There is a clear need for interventions for this population around issues of HIV and STI prevention and a videogame-based intervention could be highly scalable and culturally adaptable to other populations and languages. The scientific premise of the use of informational games to increase knowledge and intentions for health behaviors is established in the literature and the prior testing of the card game also supports this premise. The team is very qualified, if somewhat junior, to carry out the research and has a prior history of videogame development and testing. The approach is rigorous and well structured. Minor weaknesses of the study are a reliance on self-reported outcome measures and recruitment of youth who may already be engaged in services which may exclude some high-risk girls and women. Overall an excellent "highrisk, high-reward" R21 proposal that could have significant reach and impact.

Significance:
Strengths  Black adolescent and young adult women are at increased risk of HIV and disparities in HIV testing and treatment continue to exist.
 New channels to engage and impact this population are needed and video games present a significant opportunity given the frequency of use among youth.
 Preliminary work on "One Night Stan" enhances the feasibility of the proposed research and supports the intervention's scientific premise.
 Videogame-based intervention could be highly scalable -and culturally adaptable to other populations and languages.
 Group has successfully developed and tested a related videogame for at-risk boys and girls ages 11-14, providing further feasibility and capability of the proposal.
 Preliminary impact data will be very useful in comparative efficacy trial planning.
Weaknesses 1 R21 HD098031-01 7 BSPH HIEFTJE, K  Marketing and uptake for an HIV/STI based game will potentially face challenges of stigma and appeal.
 Few objective endpoint measures will be examined and reliance on self-report.

Investigator(s):
Strengths  PI is published in the areas of HIV, youth, and game development.
 Co-I is Assoc. Director of play2PREVENT lab at Yale.  Team has expertise in health behavior psychology, game development, HIV/AIDS prevention.  Co-I Fiellin has experience with current and prior NIH grants.

Weaknesses
 PI does not have prior NIH grant leadership experience and is somewhat junior.

Innovation:
Strengths  Use of a multi-player videogame as an intervention for BAYW is highly innovative.    Analysis plans are clear and appropriate.

Weaknesses
 Study population focuses on BAYW already engaged in services and afterschool programs and may miss out on high-risk unengaged persons. Suggest eliminating this criterion, as more frequent HIV testing for those with risk is advisable.
 Phase 2 testing mandates peer players be others in the study and not necessarily their true social network/peers.  Sample size estimation and/or level of confidence on estimates are not provided.
 No methods are provided for assessing and validating self-report of HIV/STI and partner HIV/STI testing.

Strengths
 Yale University and its associated CFAR have a significant history of supporting successful HIV research.
 Association with PreviewLabs is ongoing and has significant relevant experience and productivity.
 Letters of support from recruitment sites.

Budget and Period of Support:
Recommend as Requested:

CRITIQUE 3
Significance: 1 Investigator(s): 1 Innovation: 1 Approach: 5 Environment: 1 Overall Impact: The proposed work aims to develop and conduct a preliminary test of a social videogame to increase HIV/STI testing and condom use among Black adolescent girls, a population that is disproportionately affected by HIV/STIs. The scientific premise for the proposed work is strong. The proposed project builds on a promising card game developed for this purpose. The investigative team is strong. The work is innovative in its use of a social videogame aimed at HIV/STI testing and condom use in this population. The level of scientific rigor is relatively high. The use of a non-health related control condition is a particular concern given the sole reliance on self-report data.

Significance:
Strengths  The scientific premise for the proposed work is strong.  The videogame will be based on a promising card game, previously developed and pilot tested by the investigators.

MEETING ROSTER Behavioral and Social Science Approaches to Preventing HIV/AIDS Study Section
AIDS and Related Research Integrated Review Group CENTER FOR SCIENTIFIC REVIEW BSPH 07/11/2018 -07/12/2018 Notice of NIH Policy to All Applicants: Meeting rosters are provided for information purposes only. Applicant investigators and institutional officials must not communicate directly with study section members about an application before or after the review. Failure to observe this policy will create a serious breach of integrity in the peer review process, and may lead to actions outlined in NOT-OD-14-073 at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-073.html and NOT-OD-15-106 at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-106.html, including removal of the application from immediate review. Consultants are required to absent themselves from the room during the review of any application if their presence would constitute or appear to constitute a conflict of interest.