Technology Enhanced Community Health Nursing (TECH-N) to Prevent Recurrent Sexually Transmitted Infections After Pelvic Inflammatory Disease
Phase: NA
Conditions: Pelvic Inflammatory Disease (PID)
Sponsor: Johns Hopkins University

 
 
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Date: 05/01/2017 
Principal Investigator: Maria Trent, MD, MPH 
Application Number: NA_00068846 
 
 
STUDY PROTOCOL 
OFFICIAL TITLE: Technology Enhanced Community Health Nursing (TECH-N) to Prevent Recurrent 
Sexually Transmitted Infections (STIs) after Pelvic Inflammatory Disease (PID) 
NCT01640379 
Date of Document:  5/1/2017 
Date of Upload: 1/18/18 

 
 
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JHM IRB - eForm A 
 
 
 
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1. 
Abstract  
 
Pelvic Inflammatory Disease (PID) remains a serious reproductive health disorder and disease rates 
remain unacceptably high among minority adolescent girls and young adult women. Each episode 
of this upper reproductive tract infection, usually caused by a sexually transmitted infection (STI), 
increases the risk for multiple sequelae including tubal infertility, ectopic pregnancy, and chronic 
pelvic pain (CPP). Care for PID has shifted from the inpatient to the outpatient setting; however, 
our age-stratified analysis of national data shows that adolescents continued to have high rates of 
repeat STIs and CPP, regardless of treatment strategy. Our local clinical trial data has also shown 
that urban adolescents have poor adherence to the 3 day clinical follow-up visit recommended by 
the Centers for Disease Control and Prevention (CDC), are at high risk for STI at the 90-day STI 
re-screening visit, and that brief interventions in the acute care setting have positive, but modest 
effects on adherence to self-management behaviors. Inpatient treatment for PID is expensive 
without incremental increases in effectiveness when compared with outpatient treatment so 
developing outpatient strategies to improve short and long-term reproductive health outcomes, 
including recurrent STI and PID, are warranted. Community health nurse (CHN) interventions 
have been shown to increase access to appropriate resources enhance health care utilization and 
promote risk-reducing behavior among adolescents. Recent research has also shown that use of 
short messaging service (SMS) messaging can enhance clinical care by improving attention to 
medical visits, medication adherence, and communication with the health care team.  The primary 
aim of this project is to compare the effectiveness of a technology-enhanced community health 
nursing intervention (TECH-N) intervention to an optimized standard of care control group using 
randomized trial design. We hypothesize that repackaging the recommended CDC-PID follow-up 
visit using the TECH-N will be cost-effective compared with standard of care and reduce rates of 
short-term repeat infection by improving adherence to PID treatment and reducing unprotected 
intercourse. We have demonstrated that our team of trained community-oriented health 
professionals can follow adolescent girls with PID in the community and that utilizing CHNs to 
optimize treatment in the post-PID period is feasible and acceptable to adolescents and parents in 
urban communities. Our pilot using SMS communication also demonstrates that urban adolescent 
girls have access to cell phone technology, eagerly accept SMS as a communication strategy, and 
respond to health provider queries for sexual health maintenance support. We propose to enroll 350 
young women 13-21years old diagnosed with PID in Baltimore and randomize them to receive the 
TECH-N intervention which includes CHN clinical support using a single post-PID face-to-face 
clinical evaluation that incorporates an evidence based STI prevention curriculum and SMS 
communication support during the 30-day period following diagnosis (intervention group) or the 
standard of care (control group).  
 
2. 
Objectives  

 
 
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To compare the effectiveness of a PID intervention called Technology Enhanced Community Health Nurse 
(TECH-N) compared to a control group defined as optimized standard of care using a randomized control 
trial (RCT) among urban adolescents diagnosed with PID.  
 
Hypothesis 1: Adolescents in the TECH-N intervention group will have a better rate of short term (3-5 day) 
clinical follow-up compared with adolescents in the control group.  
Hypothesis 2: Adolescents with PID in the TECH-N intervention group will have a lower rate of recurrent 
STIs at 90-days compared with the adolescents with PID in the control group.  
2. To compare the cost-effectiveness of TECH-N as compared to control (optimized standard of care) for 
management of PID in the outpatient setting.  
Hypothesis 3: The TECH-N intervention will be more cost-effective than the optimized standard care 
control approach.  
Hypothesis 4: The TECH-N intervention will be more cost-effective than hospitalization using modeled 
parameters of existing cost estimates among patients with mild to moderate disease.  
 
3. 
Background (briefly describe pre-clinical and clinical data, current experience with procedures, 
drug or device, and any other relevant information to justify the research) 
Pelvic Inflammatory Disease (PID) remains a serious reproductive health disorder and disease rates remain 
unacceptably high among minority adolescent girls and young adult women. Each episode of this upper 
reproductive tract infection, usually caused by a sexually transmitted infection (STI), increases the risk for 
multiple sequelae including tubal infertility, ectopic pregnancy, and chronic pelvic pain (CPP). Care for PID 
has shifted from the inpatient to the outpatient setting for cost containment and in response to efficacy data 
from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) study that demonstrated 
similar fertility outcomes for women treated in the inpatient and outpatient setting. Unfortunately, our age-
stratified analysis of the PEACH study data shows that adolescent and young adult women continued to 
have high rates of repeat STIs and CPP, regardless of treatment strategy. Twenty percent of women less 
than 25 years experienced a repeat or persistent STI at 30 days and/or repeat PID over the 7 year follow-up 
period was associated with a 5-fold risk of CPP. Our local clinical trial data has also shown that urban 
adolescents and young adults have poor adherence to the developmentally appropriate 3 day clinical follow-
up visit recommended by the Centers for Disease Control and Prevention (CDC), are at high risk for STI at 
the 90-day STI re-screening visit, and that brief interventions in the acute care setting have positive, but 
modest effects on adherence to self-management behaviors. Previous research demonstrates that inpatient 
treatment for PID is expensive without incremental increases in effectiveness when compared with 
outpatient treatment. Our work and that of others suggest that additional outpatient cost-effective PID health 
care supports are needed for this vulnerable population to improve short and long-term reproductive health 
outcomes, including recurrent sexually transmitted infection and PID.  
 
Prior research has demonstrated that community health nurse (CHN) interventions can increase access to 
appropriate resources enhance health care utilization and promote risk-reducing behavior. We propose that 
integrating a technology component conducted by the CHN will increase appeal to adolescent females. Cell 
phone penetration among youth in the United States has increased dramatically such that teens rely on text 
messaging in their daily lives. Recent research has shown that use of SMS messaging enhances clinical care 
by improving attention to medical visits, medication adherence, and communication with the health care 
team. Our pilot data of a text messaging intervention for reproductive health clinical reminders has 
demonstrated that use of cell phones to assist urban adolescents residing in high STI prevalent communities 
with self-care is both highly acceptable and feasible.  
 
We hypothesize that repackaging the recommended CDC-follow-up visit using a technology-enhanced 
community health nursing intervention (TECH-N) with integration of an evidence-based STI prevention 
curriculum will reduce rates of short-term repeat infection by improving adherence to PID treatment and 
reducing unprotected intercourse and be more cost-effective compared with outpatient standard of care (and 
hospitalization). We have demonstrated that our team of trained community-oriented health professionals 
can follow adolescent girls with PID in the community and that utilizing CHNs to optimize treatment in the 
post-PID period is feasible and acceptable to adolescents and parents in urban communities. Our pilot using 
SMS communication also demonstrates that urban adolescent girls have access to cell phone technology, 
eagerly accept SMS as a communication strategy, and respond to health provider queries for sexual health 

 
 
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maintenance support. We propose to enroll 350 young women 13-21years old diagnosed with PID in 
Baltimore and randomize them to receive CHN clinical support using a single post-PID face-to-face clinical 
evaluation and SMS communication support during the 30-day period following diagnosis (intervention 
group) or optimized standard of care (control group).  
 
4. 
Study Procedures 
a. Study design, including the sequence and timing of study procedures   
(distinguish research procedures from those that are part of routine care). 
 
 
Overview of Study Design 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. Setting: This research study will be conducted in Baltimore, Maryland. Maryland currently ranks 
12t h in the nation for incident infections with Neisseria gonorrhea (GC) and Chlamydia (CT) among 
its citizens and there are disproportionate rates of infection among individuals residing in 
Baltimore.87 The Johns Hopkins Hospital, is geographically located in one of the highest STI 
prevalence areas in the city and institutional providers diagnose approximately 150 cases of PID to 
adolescents 21 years of age or younger each year.  
2. Participants and Recruitment: 350 adolescents, aged 13-25 years with mild-moderate PID will 
be recruited from Johns Hopkins Hospital System sites at the time of diagnosis by the TECH-N 
study staff. Johns Hopkins Hospital clinical sites include the Pediatric Emergency Department and 
the Harriet Lane General Pediatric and Adolescent Clinics.  
3. Enrollment, Consent, and Treatment: Recruiters will be onsite in each clinical setting to 
recruit patients diagnosed with PID. Flyers will be placed in physician and nursing work areas in all 
recruitment sites as a reminder of ongoing study recruitment. Patients will be screened for eligibility 
criteria, and study follow-up visits visit will be scheduled. At enrollment, a detailed review of the 
study with informed consent will be performed by the research staff. All patients who agree to 
participate will then complete an audio computerized assisted self-interview (ACASI)  to collect 
baseline information and be randomized to a research arm.  Study forms will be faxed to the project 
director at the time of enrollment and the ACASI interview will be automatically uploaded to a 
secure server for warehousing in the central database. After completion of initial study procedures 
and instruction, patients will receive remuneration of $10 and a 14-day course of 100 mg 
doxycycline tablets to be dispensed by the clinician prior to discharge according to hospital policy.  
Adolescents who are eligible for the trial and assigned to the intervention arm, but do not have a cell 
phone will be provided temporary use of a cell phone during the 1 month during which messages 
are sent.  We anticipate that this will be a small number of adolescents given that CTIA asserts that 
there is 93% cell phone penetration in the United States 56and 88% of the girls approached for our 
Depo-Text study had a cell phone for their personal use.  
4. Randomization:   Following completion of the baseline ACASI survey, each adolescent will be 
randomly assigned to either the TECH-N or control group using a permutated block design. A 
13-25 years 
with 
Mild-
Moderate 
PID 
SMS Welcome , daily 
Rx reminders x 14 
days (Compliance for 
Life©) 
TECH-N clinical visit 
3- 5-day 
14 day 
Research 
Visit 
14-day 
Research visit 
 
SMS Health 
Messages  
Days 14-30 
30-day 
visit 
Research 
Visit 
(ACAS-
Interview/ 
90-day 
Research 
Visit 
 
ACASI 
Interview 
 
 
STI 
testing 
 
30-day 
visit 
Research 
Visit 
(ACAS- 
Interview/ 
STI Test) 
●Enrollment 
●Baseline Audio 
●Computerized 
Self Interview 
(ACASI) 
●Randomization 
3-5 day Clinical 
Exam  
(Self-Arranged 
at Local Clinic) 
Standard of Care 
Eligibility 
Screen 

 
 
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permutated block design will be used to ensure group balance based on JHH sites at the end of the 
trial and period balance. The period balance will help to minimize any systematic differences 
between patients enrolling at different times during the study.88 
5. Intervention 
TECH-N 
The TECH-N intervention involves contact and follow-up by a CHN trained in disease 
intervention protocols, clinical assessment of PID, and STI prevention case management so that 
they can effectively deliver the recommended CDC follow-up in the field.  The nurse will visit the 
adolescent at 3-5 days. While the CDC recommends follow-up within 72 hours, our work suggests 
that 72 hours is an unrealistic timeline for tracking high risk girls in the community.18 The mean 
time to follow-up in our pilot study was 5.6 days (See Section 3.C.6) and is consistent with the 
follow-up evaluations timeline used for the PEACH trial.4, 35, 40 Given that only 20% of adolescents 
are making the follow-ups at all, extending the home visit target to a 3-5 day window is practical, 
ethical, and justifiable. The TECH-N intervention will be enhanced by the use of the SMS 
messaging system.  Adolescents in the TECH-N arm will be enrolled in the online Health Cloud, 
SMS© that will deliver a welcome message, a prompt to schedule the appointment for the 3-5 day 
follow-up with the TECH-N nursing team, and daily medication reminders for 14 days.  After 2 
weeks, the patient will also receive positive health reminders 3 times per week for the rest of the 
month (total 30 days).   
 
The TECH-N is based on the CDC STD Treatment Guidelines and modeled after the Johns 
Hopkins Children’s Center PID Treatment protocol for inpatient nursing staff. Integral to the 
TECH-N intervention is use of an effective behavioral intervention to reduce STI/HIV risk 
reduction behaviors.  We will use the Sister-to-Sister intervention that has a 20-minute one-on-one 
module to guide the patient through skill-based risk reduction counseling.  This intervention was 
evaluated with young African American women in an urban community with high STI rates and 
was found to increase condom use, reduce unprotected intercourse, and reduce new STIs among 
participants.68, 69 At the end of the session with the CHN, the patient will be able to 
state/demonstrate:  1.) Effective pain management; 2.) High understanding of the definition of STIs 
including the difference between cervicitis and PID, modes of transmission, signs of complications 
or problems for which they need to seek additional care, and how to prevent future PID episodes; 
3.) High understanding of optimal self-care including: a) the date, time, and place of gynecologic 
follow-up if indicated, b) the contact phone numbers for the TECH-N nurse and an MD provider, c) 
medication schedule, route, dose, and side effects, d) proper use of male and female condoms e) 
reportable signs and symptoms (e.g. fever, increasing abdominal pain, nausea/vomiting, or inability 
to tolerate medication regimen), and f) effective partner communication and negotiation strategies.
 
 
 
While the TECH-N nurse will perform the basic clinical evaluation for patients enrolled in this 
arm, the TECH-N nurse may determine that additional physician follow-up is indicated. At the end 
of the visit the TECH-N will determine a plan of action using two conditional algorithms based on 
the clinical assessment; one for patients requiring immediate attention (e.g. symptomatic worsening 
abdominal pain) and the other for patients for whom non-immediate follow-up is indicated (e.g. 
patient desires ongoing hormonal contraceptive method) The TECH-N nurse will also be given 
referrals resources to assist patients who may have other issues identified during the visit (child 
protection, housing, substance abuse in a family member, and/or other adolescent stressor, medical 
or mental health co-morbidity).  
We are using professional CHNs as the TECH-N, comparable to the STI case management 
model, rather than paraprofessionals. The TECH-N nurse will be trained on clinical assessment after 
PID, disease intervention protocols including partner notification treatment/accessing community 
resources for partner care, STD medication treatment, CDC-supported Sister to Sister STI 
prevention protocol, use of contingency contracts with adolescents, and TECH-N protocols.  The 
TECH-N nurse will also be an expert on the updated CDC PID Treatment guidelines. Despite the  

 
 
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increase in cost of a professional nurse, consistent evidence indicates that paraprofessional home 
visiting interventionists produce smaller effects compared to professionals89 and low-resource 
patients benefit most from nurse visit interventions.90 Our preliminary studies indicate that 
improved communication between an adolescent and her partner occurs with the support of a CHN 
who can educate and motivate adolescents with an STI, provide expertise on STI management, and 
encourage higher level service provision by primary care providers when problems are identified in 
the community-based environment. 79 
Control Condition 
In the control condition, patients will receive standard of care. The Johns Hopkins Children's Center 
JHCC  has optimized  PID care to ensure delivery per CDC guidelines. All clinical sites use 
electronic medical records and ordering systems to facilitate uniform care.  Dr. Trent has developed 
specialized institutional PID order sets to ensure integration of standard management protocols into 
usual clinical care.  After completion of study enrollment procedures, ACASI baseline survey, and 
collection of a vaginal swab for Mycoplasma genitalium (not usually sent as a part of standard 
practice), the clinical provider will dispense the study-supplied doxycline and discharge the patient 
with instructions for self-care using the JHH PID resources.  The team will have access to other 
medication treatment options, but in the last 5 years we have not encountered a patient who could 
not use doxycycline due to medication allergy.  Per institutional policy, patients with PID seen in 
the JHCC PED may follow-up in the JHH Harriet Lane Adolescent/Young Adult Clinic for the 72 
hour visit.  Patients can be seen in this setting for reproductive health services regardless of ability 
to pay through the clinic's Title X program.  Patient's who use this service are encouraged to 
subsequently resume care with their primary care provider given the limitations on the type of care 
that can be provided through this program.  Patient will return to the hospital for research visits at 
14 days, 30 days, and 90 days. STI testing will be performed at the 30- and 90 -day study visits.  
 
Outreach worker will contact all patients for a brief quarterly interview about their reproductive 
health status will contact via phone and/or in person ACASI. The current consent form allows 
research team to contact patients for future related studies. Patients who have already been enrolled 
will be re-contacted and verbal consent for ongoing follow-up for up to 36 months after re-
enrollment.  
 
6.Quality Control 
 
a. Training of Personnel.  All research staff, P.I. and co-investigators received training in 
Protection of Human Subjects in research studies. Research assistants and interviewing staff will be 
trained by Dr. Trent on the recruitment and consent protocol, interview surveys and confidentiality 
of data collection. The TECH-N CHN will conduct all TECH-N visits and has expertise in 
managing STIs in the local health department and in the home/community. The TECH-N will be 
trained by Drs. Butz and Trent for delivery of the intervention. 
b. Recruitment Monitoring: Research staff will be available in on site order to make patient 
referral and recruitment as easy as possible.  Research staff will monitor weekly diagnosis reports to 
determine the number of eligible patients and to ensure that none are missed.  Ongoing 
communication between Dr. Anders and Trent will enable the team to identify and address barriers 
to referral/recruitment. Research staff will also record all patients approached for study participation 
and document all referrals and track numbers of eligible participants, those who consent to 
participate and refusals. 
c. Retention Monitoring: Detailed contact information will be obtained from the patient at the time 
of the initial recruitment, including home and work numbers, cell phone numbers, email addresses, 
school attended, and the names of 2 individuals who will always know their whereabouts and can be 
contacted to locate them. Participants are also advised to call into the study office for changes in 
their living environment and will receive a small $5 gift card incentive for notification of address 
change.  While we are seeking girls residing in Baltimore Metropolitan Area at the time of 

 
 
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diagnosis, we will continue to follow subjects for study visits as long as they continue to reside in 
the Baltimore Metropolitan Area that includes surrounding counties.   
d. Treatment Fidelity: Dr. Arlene Butz who has significant expertise in community health nursing 
interventions and who has worked with Dr. Trent on several projects including the NANA 
feasibility trial will train and supervise the TECH-N staff to deliver the intervention as designed.  
She will also meet weekly with project nursing staff to ensure that they understand study procedures 
and can use effective strategies to solve problems in the field that maintain staff safety, prevent 
deviation from protocol, and ensure subject retention in the TECH-N arm of the trial. Video 
recordings of the first ten visits and thereafter 10% of TECH-N visits will be reviewed by Drs. Butz 
and Trent for consistency in the TECH-N delivery of specific PID education and management. At 
any time that an inconsistency in the delivery of protocol is noted, retraining of the TECH-N CHN 
will occur.    Dr. Trent will provide medical supervision of the TECH-N intervention and serve as 
liaison between the TECH-N nurse and community PCPs.  We will also integrate the fidelity checks 
included with the Sister to Sister intervention according to the field guide.  Weekly meetings will be 
held between the P.I., co-investigators and research staff to review recruitment and data collection. 
Cross contamination between groups will be minimized because of the nature, vehicle, and field 
location of the intervention.  Patients may receive additional advice by their doctor at the 3-5 day 
follow-up visit that assists them in completing the course of medication and other actions involved 
in self-care, but this will be evenly distributed in both groups due to the study design.  We also 
assess patient satisfaction of the TECH-N follow-up at the 30-day visit, track the number, purpose, 
and outcome of TECH-N contact between visits, and track scheduled contact behavior.   
 
Study Measurements  
a.Recruitment Screener: Includes collection of basic demographic data and the outcome of 
recruitment effort so that we can keep an accurate account of referral patients who are ineligible 
and/or refuse to participate in the intervention. 
b. Baseline ACASI Survey: We have developed a PID audio-computerized self-interview 
(ACASI) survey to collect reproductive and sexual health history, perceived barriers to treatment, 
and self efficacy data from adolescents with PID in acute care settings. The measures on the 
baseline survey contain: demographics, reproductive and sexual history, PID adherence self-
efficacy and perceived barrier scales 17, 71social provisions scale, 91, Center for Epidemiologic 
Studies Depression Scale (CES-D) as a short measure of depressive symptoms and the short-form 
survey instrument (SF-12) as a measure of health-related quality of life 42, 92   One question on 
sexual orientation will be asked to better delineate the risks for this population.  
c. Clinical Data:  The TECH-N nurse will record contact tracing data and perform a detailed 
clinical assessment that includes a pain rating scale, abdominal exam, medication usage, supportive 
care, side effects, activity level, , and patient teaching outcome.. Adolescents in the control arm will 
be given a short health provider assessment form at enrollment to be completed by the medical 
professional who re-examines at their 3-5 day clinical follow-up visit. Permission to contact those 
health providers is requested at the time of enrollment so that project staff can verify self-reported 
clinical data in the case of unreturned forms. Time to clinical re-evaluation as well as a dichotomous 
variable indicating completion of the 3-5 day visit will be generated using these measures. 
Additional clinical data collected at the 2 week research visit will include partner notification, 
results, and treatment data, sexual abstinence,  coping strategies [COPE, Carver 1997] and self-
reported medication adherence (pill counts). During this brief face-to face interview, we will also 
ask questions about partner factors and the participants’ perspective the development of preventive 
PID strategies (e.g. vaccine) and factors affecting their willingness to participate in vaccine 
research. 
d. Follow-up ACASI Surveys: The 30- and 90-day ACASI survey captures interim sexual 
behavior (current number of sexual partners, change in sexual partners since the 2 week follow-up 
assessment, change in sexual partner(s), condom use, and contraceptive use, interim diagnosis of 
STIs and pregnancy, current health status, the adolescent version of the Childbearing Motivation 

 
 
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Questionnaire (CBQ) 26, perceptions of partner influences on contraceptive decisions, and participant feelings 
about their fertility. The ACASI interviews have been used successfully in our previous trial and are 
easily administered in the field. 
e. Cost Data: The costs of administering the different interventions will be based on project records 
of hours worked, miles traveled, and other supplies with additional amounts for overhead.  The 
primary cost components for patients in both groups include the initial treatment for PID, follow-up 
therapy related to failure of initial treatment, treatments for recurrent STIs and PID, chronic pelvic 
pain, ectopic pregnancy, time lost from work/school/household management by patients and 
parents, travel to PID-related care, and any therapy or evaluation related to concerns about 
infertility by the patient. We will use these data to estimate the direct (medical costs) and indirect 
(employment (patient/parent), impairment) costs associated with PID treatment in the TECH-N and 
control interventions. Health service utilization will be derived from the longitudinal interviews, 
care utilization data (hospitalizations, emergency department visits, public health clinic visits, 
primary care provider visits), prescription and over-the-counter medication use, laboratory services, 
and radiological services (e.g. sonograms). Productivity loss will be derived using the Workplace 
Productivity and Activity Impairment (WPAI) questionnaire that has been validated as an 
instrument to collect data on absenteeism and presenteeism both for patients and for care providers. 
It can also be modified for different diseases and health states without compromising scale 
properties.93, 94 
f. Biological Measurements 
1. Collection of Biological Samples: Participants will be asked to provide a self-collected vaginal 
swab (SVS) for Mycoplasma genitalium (MG) and Trichomonas Vaginalis (TV) at baseline to 
accompany routine testing at the clinical site.  Neisseria gonorrhea (GC), Chlamydia trachomatis 
(CT), and MG will also be obtained at 30 days and 90 days and be processed at The Johns Hopkins 
University International STD and Biothreat Research Laboratory under the direction of Dr. 
Charlotte Gaydos. Laboratory tests include: 
2. CT and GC assays: The vaginal specimens will be processed and tested according to the 
APTIMA Combo 2 manufacturer’s package inserts for CT and GC.  All positive CT and NG 
APTIMA Combo 2 results from any specimen source will be confirmed using the APTIMA ACT 
and AGC assays according to instructions provided in the package inserts. Description and 
performance of these assays have been previously published.95 
3. MG and TV assays: The APTIMA vaginal swab was tested using the GEN-PROBE 
transcription mediated amplification (TMA) research assay in the same manner as for the other 
APTIMA assays. This assay targets MG rRNA and TV rRNA for detection in genital specimens.  
4. Notification of STD-positive cases: All participants with positive tests for GC, CT, MG will be 
contacted by research staff, notified of their positive test result and referred to their physician in the 
clinic for an examination and treatment. By law, the Johns Hopkins International STD Research lab 
and the research team have an obligation to report positive cases of GC/CT to the Baltimore City 
Health Department (BCHD).  Faxed reports will be sent to the health department.  
5. Partner Notification and Treatment:  All participants will be encouraged to notify their 
partners for treatment at baseline as a part of standard of care. The TECH-N will provide additional 
support and resources for notification and treatment if indicated. We will obtain self-reported 
partner notification and treatment data from each participant at the 14-day research visit. 
6. Specimen Storage: According to the JHU PID protocol, patients should have a CBC, CRP, RPR, 
and HIV testing at the time of PID diagnosis.  Three additional tube of blood (~10cc) will be drawn 
at the time of specimen collection and/or at the time of enrollment for storage and future RNA 
analysis and antibody testing.    
Sera from the TECH-N study will be analyzed using established CDC methods to determine whether 
antibody detection to pgp-3 correlates with active CT infection in PID patients. Sera will be incubated with 
chemically modified microspheres (Luminex Corp., Austin, TX) conjugated to the Ct antigens pgp3. After 
washing out unbound serum antibodies, bound antibody will be detected with biotinylated mouse anti-human 
IgG (clone H2; Southern Biotech, Birmingham, AL) and biotinylated mouse anti-human IgG4 (clone 

 
 
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HP6025; Invitrogen, South San Francisco, CA), followed by R-phycoerythrin-labeled streptavidin (SAPE, 
Invitrogen, South San Francisco, CA).  Beads are suspended in 125 µl PBS, shaken, and immediately read on 
a BioPlex 200 instrument (Bio-Rad, Hercules, CA) equipped with Bio-Plex Manager 6.0 software (Bio-Rad).  
Cut off ratios will be determined by positive and negative controls.  If lateral flow POC cartridges are made 
available by researchers at CDC (anticipated), sera will be tested on this platform as well. 
 
Vaginal 16S rRNA gene sequencing: Sequencing will be performed on stored specimens at the 
University of Maryland School of Medicine’s Institute for Genome Sciences (IGS, Brotman lab). 
We are proposing a broad 16S rRNA gene analysis of the vaginal bacterial populations. IGS has 
developed, validated and published procedures for extraction of genomic DNA from vaginal 
samples that maximize cell lysis, DNA recovery and quality.1-3 Dual index amplification and 
sequencing of the vaginal microbiota will be performed using the technique thoroughly validated 
and described by the IGS group.1 The total 16S rRNA gene copy number will be determined using a 
PanBacterial qPCR method.4  The IGS group has also demonstrated that duration of freezing does 
not impact specimens used for microbiome analyses.5 
 
1. Fadrosh DW, Ma B, Gajer P, et al. An improved dual-indexing approach for multiplexed 16S rRNA gene sequencing 
on the Illumina MiSeq platform. Microbiome. 2014;2:6-2618-2-6. 
2. Gajer P, Brotman RM, Bai G, et al. Temporal dynamics of the human vaginal microbiota. Sci Transl Med. 
2012;4:132ra52. 
3. Yuan S, Cohen DB, Ravel J, Abdo Z, Forney LJ. Evaluation of methods for the extraction and purification of DNA 
from the human microbiome. PLoS One. 2012;7:e33865. 
4. Liu CM, Aziz M, Kachur S, et al. BactQuant: an enhanced broad-coverage bacterial quantitative real-time 
PCR assay. BMC Microbiol. 2012;12:56-2180-12-56. 
5. Bai G, Gajer P, Nandy M, et al. Comparison of storage conditions for human vaginal microbiome studies. PLoS One. 
2012;7:e36934. 
 
b. Study duration and number of study visits required of research participants. Each participant 
will be followed for 90 days.  After enrollment, girls in the intervention arm will have 3 study 
visits (1 by the community health nurse within 5 days of enrollment/diagnosis of PID and 3 
research visits at 2 weeks, 30 days, and 3 months and those in the control condition will have 3 
research visits at 2 weeks and 3 months. Girls in the control condition will be advised to arrange 
their own follow-up care with their primary care provider according to current standards of care. 
 
c. Blinding, including justification for blinding or not blinding the trial, if applicable. All data will 
be managed by an institutional data management service.  While the principal investigator is 
blinded to individual study assignment; per protocol if a patient has a clinical problem while the 
CHN is in the field individual assignment will be unblended so that Drs. Butz and/or Trent will 
can assist with patient management. 
d. Justification of why participants will not receive routine care or will have current therapy 
stopped. 
e. Justification for inclusion of a placebo or non-treatment group. A control group is required to 
determine the efficacy of the intervention, however, in the control condition participants will 
receive optimized standard of care according to national and institutional guidelines. Definition 
of treatment failure or participant removal criteria. We will use an intention to treat approach so 
that all patients who enrolled will be followed until the end as our ability to maintain 
communication with them represents a key adherence behavior. Participants who indicate that 
they no longer wish to participate in the trial will be the only individuals that would be removed 
from the study. 
f. Description of what happens to participants receiving therapy when study ends or if a 
participant’s participation in the study ends prematurely. After the final study visit, participants 
will resume usual clinical care.  If a participant ends the study prematurely during the standard 
treatment period for PID care they will be encouraged to follow-up with their primary care 
provider according to national standards (Centers for Disease Control and Prevention). 

 
 
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Individuals who prematurely end their participation after the first 2 weeks; will be encouraged 
to follow-up with their primary care provider for follow-up clinical care per national guidelines 
(3-4 months after PID diagnosis) for routine STI re-screening and care. 
 
7. Mycoplasma genitalium macrolide resistance testing [Validation/Reliability Sub-study] 
 
De-identified waste samples testing positive for Mycoplasma genitalium in the main study will be 
screened for potential resistance to macrolides (Azithromycin) utilizing a novel high-resolution 
melting curve analysis (HRMA) assay that inerogates a region of the 23S rRNA gene known to 
contain point mutations conferring macrolide resistance to M. genitalium using the following 
protocol in the Johns Hopkins International STI and Biothreat Laboratory. 
  
DNA from positive M. genitalium samples will be extracted via the Roche MagNA Pure LC robot 
utilizing the DNA I isolation kit following the manufacturer instructions with 200 µl of sample 
input and 100 µl of elution volume. Lightscanner PCR for melting curve analysis: Primers for 
melting curve analysis are as follows: Mg23SF 5’CGGTGAAATCCAGGTACGG3’ and MG23SR 
5’ CAGTAAAGCTTCACGGGGTCT3’, with the following sequence as the predicted PCR 
product: 
5’CGGTGAAATCCAGGTACGGGTGAAGACACCCGTTAGGCGCAACGGGACGGAAAGAC
CCCGTGAAGCTTTACTG3’, with the base pairs responsible for macrolide resistance highlighted 
in red.  The primers and predicated PCR product is modified from J Clin Microbiol 2014, 52 (5), 
1549-1555.  Lighscanner reactions will be prepared using the following: 4 µl of 2.5X Lighscanner 
Mix, 1 ul of each primer at 1.5 µM concentration, 1 µl of Lightscanner grade water, 1 µl of 
temperature calibrators at 1.5 µM and 2 µl of template DNA.  Reaction conditions will consist of: 
95°C for 5 minutes followed by 45 cycles of 95°C for 10 seconds, 58°C for 30 seconds and 72°C 
for 1 minute, followed by a 4°C cooling step for plate handling. HRMA analysis will be performed 
on Lighscanner plates using the Lightscanner (Biofire Diagnostics) per manufacturer instructions 
for small amplicons.  Macrolide resistance will be determined by shifts in melting temperatures of 
generated PCR products compared to control reactions containing both wild type, and mutant 23S 
rRNA sequences for M. genitalium. 
 
Since the results from resistance testing will not be available for patient and/or provider use as these 
methods have not been validated and/or approved for use by the FDA.   
 
 
5. 
Inclusion/Exclusion Criteria 
 
 
Inclusion Criteria: Eligible participants should be aged 13-21 diagnosed with mild-moderate PID, 
given an outpatient treatment disposition, permanently reside in the Baltimore Metropolitan area, 
and be willing to sign informed consent (including communication with the adolescent’s primary 
care provider). Informed consent includes being willing to complete study procedures; including 
randomization and community-based follow-up by our team.  
 
Exclusion Criteria: Patients who are pregnant, have a concurrent diagnosis of sexual assault, or are 
unable to communicate   
 
6. 
Drugs/ Substances/ Devices 
a. The rationale for choosing the drug and dose or for choosing the device to be used.  N/A 

 
 
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b. Justification and safety information if FDA approved drugs will be administered for non-FDA 
approved indications or if doses or routes of administration or participant populations are 
changed. N/A 
c. Justification and safety information if non-FDA approved drugs without an IND will be 
administered.  N/A 
 

 
 
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Date: 11/29/11 
Principal Investigator: Maria Trent, MD, MPH 
Application Number: ___________ 
 
 
7. 
Study Statistics 
a. Primary outcome variable. Adherence to 3-5 day visit; STI infection rate at 3 months 
b. Secondary outcome variables. Cost differentials between study groups 
c. Statistical plan including sample size justification and interim data analysis. 
 
Sample Size and Power: We conducted power analyses for Specific Aim 1, hypothesis 2. As 
described in the Preliminary Studies, we conducted a longitudinal analysis of data to examine 
repeat STIs/PID following PID diagnosed in pediatric ambulatory settings in Baltimore. The 
results suggested that at 3 months, the STI positivity rate was 25% and thus we will assume a 
25% STI infection rate for the control group. Our preliminary data also suggests that at baseline 
we will be able to recruit approximately 175 participants in each arm for a total of 350 
participants. We expect about 30% attrition over the study period and thus each study arm will 
have an effective sample size of 122.5 participants, for a total of 245 participants. Using these 
assumptions, our power calculations suggest that we will have 80% power to detect a relative 
risk of 1.66.  
Data Analysis Primary Aim:  
Overview: The overall approach will be an intention-to-treat analysis. To test the hypotheses, in 
addition to data cleaning and exploratory data analysis we will first need to address the 
challenges presented by the study design. The challenges include assessing the “success” of the 
randomization scheme, testing for differences in basic demographic characteristics between the 
clinical sites, and exploring missing data due to survey non-response and due to attrition. The 
plan for addressing each of the challenges and for hypothesis testing is described below. Data 
analysis for hypotheses 1 and 2 will be performed using STATA or comparable statistical 
software and analysis for hypothesis 3 will be performed using Tree Age software.  
Testing for Differences by Randomization Assignment and Clinical Site: Comparability of 
the randomization assignments will be statistically assessed. If the randomization assignment 
does not result in equivalent groups or if there are significant differences by clinical site, we will 
adjust for nonequivalence in hypothesis testing (see below).  
Missing Data due to Survey Non-response: The extent of data missing due to survey non-
response will be assessed and if extensive, we will explore using imputation to deal with the 
missing data. We will take care to enter into imputation procedures with an exploratory yet 
principled approach as a naïve or unprincipled imputation method may create more problems 
than it solves distorting estimates standard errors and hypothesis tests. We will explore the use 
of Rubin’s multiple imputation procedure, as one example.  
Attrition Analysis: We will examine the extent of attrition over the course of the study. In 
particular, we will examine whether missing values are not missing at random and are non-
ignorable. Since the study participants who drop out from the study may be different from those 
who remain, the propensity score method will be used to reduce selection bias, balancing the 
covariates in the data analysis.  
 
Hypothesis testing:  
In Aim 1, Hypothesis 1, we will assess whether adolescents with PID in the TECH-N 
intervention show greater adherence, defined as adherence to the 3 -5 day follow-up visit, 
compared to adolescents with PID in the control group. We will conduct a logistic regression 
analysis to determine whether the intervention group showed greater short-term adherence rate 
compared to the control group including potential factors that may affect the difference in rates. 
In Hypothesis 2, we will determine whether adolescent women with PID provided with the 
TECH-N intervention have a lower rate of recurrent STIs at 90 days compared to adolescents in 

 
 
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the control group. We will conduct a logistic regression analysis to determine whether the 
intervention group showed a lower rate of recurrent STIs at 90 days compared to the control 
group, including potential factors that may affect the difference in rates. In an exploratory 
analysis, we will also determine whether the adolescent women with PID in the TECH-N group 
have on average over time – baseline, 30-day, and 90-day- lower rates of recurrent STIs as 
compared to the intervention group. This initial analysis will use logistic regression and 
generalized estimating equations to handle the correlation of multiple measures within a person 
over time. We will also explore the group – intervention vs. control – trajectories over time to 
determine whether the two groups have statistically different slopes of recurrent STIs. We will 
also explore stratifying the curves by measures such as race/ethnicity and level of poverty.  In 
Aim 2, Hypothesis 3, we will determine whether the TECH-N intervention is more cost-
effective than the control for the prevention of recurrent STIs and PID-related complications. 
The cost evaluation will examine the net difference in costs between TECH-N and control 
groups in relation to prevention of 1) recurrent STIs (including PID) and 2) PID-related 
complications (e.g. re-hospitalization, medical visits, ectopic pregnancies). The difference in 
costs will account for the net difference between the outpatient strategies in use of medical 
services and indirect costs for PID treatment. The analysis will also consider savings in medical-
care costs and indirect costs from prevention of the outcome variables. Two types of outcomes 
can be created. While the workplace and home productivity improvements are not the only 
monetary improvements associated with better care, a cost-benefit analysis can be performed 
simply comparing the excess costs of TECH-N with the medical care savings and productivity 
gains from cases averted. The distribution around the point estimate of the net benefits can be 
ascertained using a bootstrapping approach to account for the lack of the normal distribution 
that is likely in a net benefit calculation. We can also extend the analysis to a cost-effectiveness 
evaluation if TECH-N remains more expensive even after accounting for medical care costs and 
productivity loss averted. In this case, we can measure the dollars spent per case of STI averted 
over the relevant time period. We can also use published parameters to determine how the 
TECH-N intervention compares to hospitalization. Decision makers can then focus their 
attention on whether the added costs appear to be worth the health improvement. In this case, 
we could also use a bootstrapping analysis to calculate the distribution of the ICER. 
 
Analyses will be performed to correlate positive antibody for pgp-3 with active CT infection at baseline 
for females in the TECH-N study. 
 
a. Early stopping rules.  A data safety monitoring board consisting of senior researchers in related 
fields and who have no direct involvement with the study will review study data including 
preliminary outcomes and adverse events. While all enrolled girls will be followed until the end 
of the follow-up period, preliminary analyses that demonstrate significant adverse findings prior 
to reaching sample size the team will discuss discontinuation of the trial. However, given the 
multiple pre-determined hypotheses related to cost-effectiveness, we will need to complete data 
collection even if we determine that significant findings for the primary outcomes 
(adherence/STI reduction). 
 
8. 
Risks 
a. Medical risks, listing all procedures, their major and minor risks and expected frequency.  
There are no medical risks to participation in this study.  Collection of self-collected vaginal 
specimens, as a part of routine care, may produce some discomfort during specimen collection, 
particularly if infected.  While we are examining STI infection as our outcome, girls in the trial 
are being tested according to the recommendations for re-screening and the risk is no greater 
than if done in traditional clinical care and/or public health settings. There is potential for 
breeches of confidentiality, but miniscule given the limited number of personnel with access to 
participant information. While the study will attempt to preserve patient confidentiality, this 

 
 
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study involves community based and/or home visits for most adolescents therefore disclosure of 
study participation is encouraged. In the pilot study for this work and the our published RCT of 
over 150 adolescents, we followed adolescent girls with PID in their home by either nursing 
staff or disease intervention specialists as a part of our public health approach to PID using 
structured outreach protocols without complaints of undue exposure, confidentiality breach, or 
complaints by parents/guardians about their adolescent's participation in the study.    
 
 
b. Steps taken to minimize the risks. 
 
All participants will provide informed consent and will be informed that their participation in 
the study will have no effect on subsequent medical care at any referral site. All patient data will 
be kept confidential and secure.  A expert advisory panel will evaluate the progress of 
interventional trial(s), including periodic assessments of data quality and timeliness, participant 
recruitment, accrual and retention, participant risk versus benefit, performance of trial sites, and 
other factors that can affect study outcome. The research team on this project has been educated 
in the protection of human research participants and the treatment of protected health 
information as evidence by completion of their institutional compliance courses.  New research 
staff will complete the Johns Hopkins Committee on Clinical Investigation courses as a part of 
their training and be added to the protocol for review accordingly. 
 
Maryland state law permits an adolescent under 18 years old to consent herself for research 
when receiving reproductive care and most adolescents being seen in ambulatory sites at Johns 
Hopkins seek care   unaccompanied by a parent, we will not require parental consent for 
participation in this study.  The Johns Hopkins Institutional Review Board approved this 
approach for the successful pilot of this study design.  Due to the longitudinal approach 
involved in this study, we encourage adolescents to keep parents informed about their 
participation in the study. As with the pilot study, we will explain to the adolescents that while 
they can consent to participate in the study, their parent would need to approve a visit by a 
health professional within their home.  When the nurse interventionist contacts the adolescent to 
schedule the appointment, she will offer to explain to the parent that her daughter agreed to 
participate in a study through the Johns Hopkins University and that we would like to come to 
the home to complete the study visit. Oral consent via phone or in-person would be equivalent.  
If an adolescent wants to participate but expresses any concerns about home visits at enrollment 
or during the follow-up call with the nurse interventionist, the option will be made for visits to 
occur at an alternate location. As a part of our previous work, patients could meet the patient at 
the clinic, a relative's home, and/or a Baltimore City Health Department school health clinic.   
 
Collection of self-collected samples is a routine part of clinical care. There are no additional 
steps, which can be taken to reduce discomfort associated with provision of a sample. Only 
members of our evaluation team will have access to the patient chart and data extraction forms.  
Involved personnel will be trained and committed to confidentiality and protection of patient 
rights and have received formal training through the institution.  No identifying patient data will 
be included in any of the presentations or publications that may be generated as a consequence 
of this study.  Our database will not contain any patient identifiers, as all participants will be 
assigned unique identifiers. Further, the study design provides for several alternatives for study 
participation that allow the adolescent to make decisions about non-participation, participation 
with parental awareness/involvement, and participation through alternate community outreach 
strategies. By offering these alternative strategies, our team is ensuring protection of privacy as 
afforded by law while setting the stage for adult involvement that could potentially facilitate 
improved clinical outcomes for the patient.  We will document the strategy to be employed by 

 
 
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the team at the time of recruitment and evaluate potential differential impacts observed based on 
follow-up approach.  Even if adolescents randomized to the TECH-N intervention arm choose 
not to have the visit done at home, they will still have their 3-5 day follow-up conducted by the 
TECH-N nurse and access to him/her during the follow-up period as all other participants in this 
arm.  We will uses SMS services from HealthCloudSMS, a ZeroSum Health, LLC product, 
provides a reliable, secure, and cost-effective solution for researchers to implement text message 
based interventions. ZeroSum Health Security Policies meet or exceed HIPAA’s privacy and 
security standards. The research team will access HealthCloudSMS through a secure web portal, 
where we can track participant progress. All data is encrypted before transmission, protected 
with SSL encryption during transmission, and is stored with 256-bit AES encryption on a 
dedicated, secure data server. The web application is hosted on a separate, secure application 
server. Both servers can only be accessed using key-based authentication (a 2048 bit RSA key 
pair), which facilitates highly secure access to ensure that PHI and all data is protected. 
HealthCloudSMS employs highly restrictive network access, a rigorous data backup protocol, 
and strong auditing capabilities, including detailed activity logs of database and application 
access. Finally, all participants will be encouraged to use standard safety mechanisms such as a 
pin or password to lock access to their cell phones by others.   
 
c. Plan for reporting unanticipated problems or study deviations.  
Any unanticipated problems or adverse events will be reported to the IRB immediately. 
Deviations from the original study protocol will be requested through a change in research 
request. 
 
d. Legal risks such as the risks that would be associated with breach of confidentiality.  
 
There are no anticipated legal risks associated with study participation. We have been following 
girls in the community for many years and in their homes without consequence as we have put 
safeguards in place to protect confidentiality as outlined above. 
 
e. Financial risks to the participants. There are no anticipated financial risks to participations that 
are unaccounted for in the support and remuneration plan. 
 
 
9. 
Benefits 
a. 
Description of the probable benefits for the participant and for society. 
 
The proposed research is the first to measure, in a randomized clinical trial, the effectiveness of a 
technology enhanced community nursing strategy for short-term clinical management of PID in 
adolescents. If successful, this study will yield data to support adoption of an alternative cost 
conscious, but effective strategy for managing adolescents with a complicated STI in the outpatient 
setting in accordance with CDC recommendations. To date, the data clearly demonstrates that 
adolescents need additional supports to self-manage PID in the outpatient setting. While adolescents 
engage in technology use, our preliminary work suggests that this is more likely when there is 
concurrent face-to-face interaction and/or a relationship that establishes a context for 
communication. This intervention provides a structure for the delivery of the necessary follow-up 
care, overcomes many of the barriers (e.g. lack of medical home, transportation) that often 
undermine adolescents ability to adhere, and provides for protection of confidentiality. The study 
also explores untested theories about acceptability of adult involvement after diagnosis of PID and 
the use of technology to communicate with a health provider during an acute medical illness in a 
community where the reproductive life course for young women is disproportionately influenced by 

 
 
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STI histories and for whom the cost-effectiveness thresholds for cost-effectiveness of a new 
intervention have not yet been determined.  
 
Antibody testing may result in a viable CT point of care test in the future which will optimize 
clinical care in real time and prevent PID in general population samples.  
 
10. 
Payment and Remuneration 
 
Patients will receive a $10 gift card at enrollment and $10 for completed face-to-face research visit 
(14, 30,and 90 days) plus an addition $10 for each STI sample (N=3)provided according to the 
schedule as outlined below. Adolescents in the TECH-N arm will not receive remuneration for the 
3-5-day clinical care visit given the current standards of care and because adherence to the CHN 
clinical visit is a behavior under study that must be made without any form of additional incentive. 
Patients will be remunerated $10 for each completed and/or in-person quarterly interview after the 3 
month research visit.  Participants who complete all 4 interviews for the first year will receive an 
added bonus of $50.   
Adolescents who are eligible for the trial and assigned to the intervention arm, but do not  have a 
cell phone will be provided with a disposable cell phone during the 1 month during which messages 
are sent by CFL. We anticipate that this will be a small number of adolescents given that CTIA 
asserts that there is 93% cell phone penetration in the United States 56 and 88% of the girls 
approached for our Depo-Text study at JHU had a cell phone for their personal use. 96 We have 
found, however, that maintenance of service can be a problem for low-income youth. We will also 
encourage enrolled participants to notify us if their cell phone service is discontinued during the 
intervention month so that we can ensure the delivery of CFL messages through use of either a cell 
phone renewal card and/or use of a disposable phone. The rates of remuneration for interviews and 
specimen collection are based on our previous field experience with adolescents and young adults in 
Baltimore who often have competing agendas (e.g. part-time employment) that may preclude them 
from participating in study visits.  
 
11. 
Costs 
a. 
Detail costs of study procedure(s) or drug (s) or substance(s) to participants and identify 
who will pay for them.   
 
There are no anticipated costs to participants that are unaccounted for in the support and 
remuneration plan for the study and/or usual care. 
 
 
 

 
3.D.9.  Sample Size and Power: We conducted power analyses for Specific Aim 1, hypothesis 2. As 
described in the Preliminary Studies, we conducted a longitudinal analysis of data to examine repeat STIs/PID following 
PID diagnosed in pediatric ambulatory settings in Baltimore.  The results suggested that at 3 months, the STI positivity 
rate was 25% and thus we will assume a 25% STI infection rate for the control group.77   Our preliminary data also 
suggests that at baseline we will be able to recruit approximately 175 participants in each arm for a total of 350 
participants. We expect about 30% attrition over the study period and thus each study arm will have an effective sample 
size of 122.5 participants, for a total of 245 participants. Using these assumptions, our power calculations suggest that we 
will have 80% power to detect a relative risk of 1.66. (Figure3.D.7) 
Figure 3.D.9.  Power by Relative Risk for Specific Aim 1, hypothesis 2 by Study Arm Sample Size 
 
1 
 
0.9 
 
0.8 
 
0.7 
 
0.6 
 
123 
105 
n 
96 
 
0.5  
1.4  
1.5  
1.6  
1.7  
1.8  
1.9  
2.0 
Relative risk 
 
3 D.10. Data Analysis Primary Aim: 
Overview: The overall approach will be an intention-to-treat analysis.  To test the hypotheses, in addition to data cleaning 
and exploratory data analysis we will first need to address the challenges presented by the study 
design. The challenges include assessing the “success” of the randomization scheme, testing for differences 
in basic demographic characteristics between the clinical sites, and exploring missing data due to survey non- response 
and due to attrition. The plan for addressing each of the challenges and for hypothesis testing is described below.  Data 
analysis for hypotheses 1 and 2 will be performed using STATA or comparable statistical software and analysis for 
hypothesis 3 will be performed using Tree Age software. 
Testing for Differences by Randomization Assignment and Clinical Site:  Comparability of the 
randomization assignments will be statistically assessed. If the randomization assignment does not result in equivalent 
groups or if there are significant differences by clinical site, we will adjust for nonequivalence in hypothesis testing 
(see below). 
Missing Data due to Survey Non-response:  The extent of data missing due to survey non-response will be assessed and 
if extensive, we will explore using imputation to deal with the missing data. We will take care to enter into imputation 
procedures with an exploratory yet principled approach as a naïve or unprincipled imputation method may create more 
problems than it solves distorting estimates standard errors and hypothesis tests.97 We will explore the use of Rubin’s 
multiple imputation procedure, as one example. 
Attrition Analysis:  We will examine the extent of attrition over the course of the study. In particular, we will examine 
whether missing values are not missing at random and are non-ignorable.  Since the study participants who drop out from 
the study may be different from those who remain, the propensity score method will be used to reduce selection bias, 
balancing the covariates in the data analysis.98 
Hypothesis testing: 
In Aim 1, Hypothesis 1, we will assess whether adolescents with PID in the TECH-N intervention show greater 
adherence, defined as adherence to the 3 -5 day follow-up visit, compared to adolescents with PID in the control group. 
We will conduct a logistic regression analysis to determine whether the intervention group 
showed greater short-term adherence rate compared to the control group including potential factors that may 
affect the difference in rates. In Hypothesis 2, we will determine whether adolescent women with PID 
provided with the TECH-N intervention have a lower rate of recurrent STIs at 90 days compared to adolescents in the 
control group. We will conduct a logistic regression analysis to determine whether the intervention group showed a lower 
rate of recurrent STIs at 90 days compared to the control group, including potential factors that may affect the difference in 
rates. In an exploratory analysis, we will also determine whether the adolescent women with PID in the TECH-N group 
have on average over time – baseline, 30-day, and 90-day- lower rates of recurrent STIs as compared to the intervention 
group. This initial analysis will use logistic regression and 

 
 
 
 
 
 
generalized estimating equations to handle the correlation of multiple measures within a person over time. We 
will also explore the group – intervention vs. control – trajectories over time to determine whether the two 
groups have statistically different slopes of recurrent STIs. We will also explore stratifying the curves by 
measures such as race/ethnicity and level of poverty. 
In Aim 2, Hypothesis 3, we will determine whether the TECH-N intervention is more cost-effective than 
the control for the prevention of recurrent STIs and PID-related complications. The cost evaluation will examine 
the net difference in costs between TECH-N and control groups in relation to prevention of 1) recurrent STIs 
(including PID) and 2) PID-related complications (e.g. re-hospitalization, medical visits, ectopic pregnancies). 
The difference in costs will account for the net difference between the outpatient strategies in use of medical 
services and indirect costs for PID treatment. The analysis will also consider savings in medical-care costs and 
indirect costs from prevention of the outcome variables. Two types of outcomes can be created. While the 
workplace and home productivity improvements are not the only monetary improvements associated with better 
care, a cost-benefit analysis can be performed simply comparing the excess costs of TECH-N with the medical 
care savings and productivity gains from cases averted. The distribution around the point estimate of the net 
benefits can be ascertained using a bootstrapping approach to account for the lack of the normal distribution that 
is likely in a net benefit calculation. We can also extend the analysis to a cost-effectiveness evaluation if TECH-
N remains more expensive even after accounting for medical care costs and productivity loss averted. In this 
case, we can measure the dollars spent per case of STI averted over the relevant time period. We can also use 
published parameters to determine how the TECH-N intervention compares to hospitalization. Decision makers 
can then focus their attention on whether the added costs appear to be worth the health improvement.  In this 
case, we could also use a bootstrapping analysis to calculate the distribution of the ICER.