Clinical trial NCT03255941
Conditions: Contraception
Keywords: FWW (Family Welfare Worker) LHW (Lady Health Worker) DMPA (Depot medroxyprogesterone acetate or Depo Provera) DMPA IM (Depo Provera intramuscular injection) SP (Sayana Press subcutaneous injection) Contraception CBA2I (Community-based access to injectables) Sayana (Sayana Press) JHPIEGO (Johns Hopkins Program for International Education in Gynaecology and Obstetrics) Sayana
Sponsor: FHI 360
Start date: 2018-03-19; Completion date: 2018-07-23
Enrollment: 460 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized controlled trial comparing lay Lady Health Workers (Lay Health Workers) with Family Welfare Workers (Clinically- trained Health Workers) on quantitative measures of safety and effectiveness of Depo Provera and Sayana Press provision in a clinic setting. This comparative trial will test the non-inferiority hypothesis that Lady Health Workers are just as competent as clinically-trained Family Welfare Workers in screening and counseling first-time injectable users. These first time users will also be randomly assigned to receive intramuscular or subcutaneous injections of DMPA.

Detailed description:
FHI 360 and Jhpiego in collaboration with USAID, Aga Khan University (AKU) and the Government of Sindh province propose a randomized controlled trial (RCT) to provide evidence that could change current policies in Pakistan that forbid initiation of DMPA by Lady Health Workers (LHWs). Positive findings on the safety and effectiveness of LHW-initiation of DMPA may also prompt the WHO to consider modifying the recommendation for targeted M\&E for lay health worker provision of intramuscular injectable contraceptives. The trial will compare the screening and counseling of (LHWs)-the main lay health worker cadre--with that of Family Welfare Workers (FWWs) who are clinically-trained. The Government of Sindh province also expressed interest in introducing Pfizer's subcutaneous form of Depo Provera, Sayana Press® (SP) in Pakistan, which could simplify administration of injectable contraceptives. As such, an SP arm will be included in the trial, which will be facilitated by relevant training of LHWs and FWWs by Jhpiego and stocks provided by a special USAID procurement, since the registration process for SP in Pakistan is ongoing. A successful RCT demonstrating the non-inferiority of LHWs vis á vis FWWs on first-dose initiation of Depo Provera IM (DMPA IM) and (SP) would facilitate efforts to expand CBA2I in Pakistan, and in turn improve access to family planning services for a potentially large number of underserved women.

Arms: arm 1: Urban Clinic Provider providing DMPA or Sayana Press arm 2: Urban Lay Provider providing DMPA or Sayana Press arm 3: Rural Clinic Provider providing DMPA or Sayana Press arm 4: Rural Lay Provider providing DMPA or Sayana Press
Interventions: intervention 1: DMPA intervention 2: Sayana Press
Intervention descriptions: intervention 1: The safety and effectiveness of provision of injectable contraception will be compared between providers' screening and counseling for eligibility to use DMPA. intervention 2: The safety and effectiveness of provision of injectable contraception will be compared between providers' screening and counseling for eligibility to use Sayana Press

Protocol documents:
Prot_000.pdf: 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee 8/8/17 
Study #1035709-1, Version 3.0 
 
i 
Research Protocol 
 
 
 
 
 
Title: A randomized controlled trial of safety and effectiveness of Depo Provera intramuscular 
and subcutaneous administration comparing lay Lady Health Workers with clinically-trained 
Lady Health Visitors in Pakistan 
 
Study #: 1035709 
 
Study Sponsor: Pfizer Foundation 
 
FHI 360 Project Leader: Dawn Chin-Quee 
 
Study Site(s): Sindh, Pakistan 
 
Principal Investigator: Dr. Sarah Saleem 
 
Date: June 19, 2017 
 
Version 3.0 


 
 
 
ii 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
Study Summary 
 
Title: A randomized controlled trial of safety and effectiveness of Depo Provera intramuscular 
and subcutaneous administration comparing lay Lady Health Workers with clinically-trained 
Lady Health Visitors in Pakistan  
 
Study #: 1035709 
 
Design: Randomized controlled trial comparing Lady Health Workers with Lady Health Visitors 
on quantitative measures of safety and effectiveness. 
 
Population: Lady Health Workers and Lady Health Visitors trained to initiate intramuscular and 
subcutaneous Depo Provera use. DMPA clients of trained Lady Health Workers and Lady Health 
Visitors. 
 
Study Duration: 12 months 
 
 


 
 
 
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Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
 
 
Primary Objective: 
To assess whether the community health worker cadre, Lady Health 
Workers (LHWs) in Pakistan can screen and initiate women on 
intramuscular and subcutaneous Depo Provera injections as safely and 
effectively as their clinically-trained counterparts, Lady Health Visitors 
(LHVs). 
Primary Outcomes: 
• 
Proportion of Lady Health Workers and Lady Health Visitors 
that appropriately screen women for DMPA use; 
• 
Proportion of Lady Health Worker and Lady Health Visitor 
clients that report discussion with their respective providers on 
side effects, danger signs, advantages and disadvantages of 
DMPA use;  
• 
 Proportion of Lady Health Workers and Lady Health Visitors 
that demonstrate appropriate injection technique 
• 
Proportion of Lady Health Workers and Lady Health Visitors 
that report needle stick injuries; 
• 
Proportion of Lady Health Workers that properly maintains a 
client (re)injection log.  
Secondary Objective: 
To assess whether DMPA clients of Lady Health Workers and Lady 
Health Visitors are equally satisfied with their respective providers and 
the family planning services they provide. 
Secondary Outcomes: 
• 
Satisfaction with the method; 
• 
Satisfaction with the services received from the provider; 
• 
Reports of client ability to speak freely and ask questions of 
provider; 
• 
Friendly and respectful behavior toward client. 
Study Sites: 
Five urban sites in Karachi; five rural sites in Thatta district. 


 
 
 
iv 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
Abbreviations and Acronyms 
 
 
AKU 
 
Aga Khan University 
CBA2I  
community-based access to injectables 
CPR 
 
contraceptive prevalence rate 
DMPA  
depot medroxyprogesterone acetate 
FP 
 
family planning 
HQ 
 
headquarters 
ICF 
 
informed consent form 
IM 
 
intramuscular 
IRB 
 
institutional review board 
LHV 
 
lady health visitor 
LHW 
 
lady health worker 
LTF 
 
lost-to-follow-up 
mCPR  
modern contraceptive prevalence rate 
OIRE 
 
Office of International Research Ethics 
PI 
 
principal investigator 
PNC 
 
Pakistan Nursing Council 
RA 
 
research assistant 
SAP 
 
statistical analysis plan 
SP 
 
Sayana Press® 
 
 
 


 
 
 
v 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
Table of Contents 
Study Summary ................................................................................................................................ ii 
Abbreviations and Acronyms .......................................................................................................... iv 
Table of Contents ............................................................................................................................. v 
I. 
Introduction ............................................................................................................................. 1 
II. 
Objectives and Outcomes ........................................................................................................ 3 
III. 
Methodology ....................................................................................................................... 5 
IV. 
Data management and analysis plan ................................................................................ 15 
V. 
Research utilization and dissemination activities ............................................................. 16 
VI. 
Protection of human subjects ........................................................................................... 17 
VII. 
Appendix ............................................................................................................................ 21 
VIII. 
Endnotes ............................................................................................................................ 24 
 
 
 


 
 
 
1 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
I. 
Introduction  
Task sharing of health services by higher and lower level cadres of providers has been adopted as a 
pragmatic response to human resource shortages in many developing countries.1,2 Family planning 
service delivery has benefited enormously from this strategy by increasing access to contraception--
particularly to women in rural and underserved areas.3 Access to a wider range of methods and of 
providers, such as the provision of long-acting and permanent methods (LAPMs) by clinical and health 
officers;4 long-acting reversible contraceptives (LARCs) by midwives, auxiliary nurses and some lay 
health workers;5,6,7 and injectable contraceptives by community health workers,8,9 are the products of 
task sharing. In fact, the popularity of injectables in sub Saharan Africa combined with the practicality of 
lay health worker provision of the method has increased modern contraceptive use in many of these 
countries.10 
Task sharing is supported by the World Health Organization (WHO), formalized in its guideline 
document, OptimizeMNH11 and reiterated in the Safe Abortion guidelines.12 Recommendations in this 
key guideline document are based on and supported by evidence obtained through systematic reviews 
of research--including qualitative and case studies--and programmatic experience. As shown in the 
figure in Appendix 1, the cadre of health provider and the contraceptive method in question are 
organized by four categories of guidance—recommended, recommended with targeted monitoring and 
evaluation (M&E), consider in the context of rigorous research, and recommend against. The guidelines 
recommend provision of all methods: tubal ligation, vasectomy, intrauterine devices (IUDs), implants 
and injectables by associate clinicians and non-specialist doctors. However, limitations are placed on the 
methods that midwives, nurses, auxiliary midwives, auxiliary nurses and lay health workers may provide. 
For example, there are no restrictions on the provision of oral contraceptive pills and condoms (which 
are not shown in Appendix 1) by lay health workers, but the provision of tubal ligation, vasectomy and 
IUDs is recommended against; implants can be provided in the context of rigorous research; and 
provision of injectable contraception using standard syringes for intramuscular injections should be 
accompanied by targeted M&E. Currently, there are no guidelines for subcutaneous contraceptive 
injectables. 
These recommendations are subject to revision if new evidence becomes available and meets WHO 
standards. WHO uses the GRADE (Grades of Recommendation Assessment, Development and 
Evaluation) approach to assess the quality of the evidence—one of the factors that contributes to the 
strength of the recommendation. Currently, the evidence supporting lay health worker provision of 
injectable contraception, while strong and bolstered by many pilot studies and programs worldwide, 
does not include a randomized controlled trial (RCT).7 An RCT constitutes the highest level of evidence in 
the WHO research framework; thus, a trial demonstrating that lay health workers can just as safely and 
effectively initiate  injectable contraception  as clinically-trained cadres of health providers could modify 
the recommendation of targeted M&E for intramuscular injections.   
FHI 360 and Jhpiego in collaboration with USAID, Aga Khan University (AKU) and the Government of 
Sindh province propose a randomized controlled trial (RCT) to provide evidence needed not only to 
change current policies in Pakistan forbidding initiation of DMPA by LHWs, but also for WHO to consider 


 
 
 
2 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
modifying the recommendation for targeted M&E for lay health worker provision of intramuscular 
injectable contraceptives. The trial will be conducted in Pakistan with Lady Health Workers (LHWs)—the 
main lay health worker cadre. Given the very large number of LHWs—perhaps as much as 150,00013--
this trial could just as importantly facilitate access to injectable contraception for thousands of Pakistani 
women, potentially increasing the country’s modern contraceptive prevalence rate (mCPR). 
The Pakistani Context 
According to the latest Pakistan Demographic and Health Survey (PDHS 2012-13),14 the contraceptive 
prevalence rate (CPR) for any method among currently married women is 35%; the mCPR is 26%. Female 
sterilization and condoms are the predominant modern methods at 9% each, with injectables at 3%, and 
pills and intrauterine devices (IUDs) at 2% each (no data provided on subdermal implants). The public 
sector, which includes LHWs, currently provides 46% of family planning methods, while the private 
sector provides 35%.  
Knowledge of family planning methods in Pakistan is universal at 99% for women and 96% for men. For 
both currently-married men and currently-married women, the most commonly known methods are the 
pill (85% and 95%, respectively) and injectables (82% and 95%, respectively), along with awareness of 
condoms reported by currently-married men (89%) and female sterilization reported by currently-
married women (91%). Unmet need for family planning among currently married women has fallen 
since the 2006-07 PDHS from 25% to 20%, but it is 22% in rural areas where met need for family 
planning is also predictably lower in rural (31%) than urban areas (45%).   
The National Program for Family Planning and Primary Health Care, also known as the Lady Health 
Worker Program, was established to provide rural communities and slum areas with essential primary 
health care services, including maternal, newborn and child health care; family planning services; and 
integration of other vertical health promotion programs, such as polio vaccinations. The most common 
LHW services received by women were child vaccinations (20%), treatments for minor ailments (7%), 
contraceptive supplies (7%), and information on maternal and child health (4%).11 In recent years, the 
workload of LHWs has increased enormously. For that reason, one of Pakistan’s FP2020 goals is to re-
focus priority on family planning services, which would also enable the government to meet its goal of 
increasing the CPR to 55% by 2020 and an mCPR of 36.5%.15,16 Additionally, provinces have set their own 
goals, such as Sindh Province with a target of 45% CPR for 2020. 
LHWs receive 18 months of didactic and practicum training--many more months than CHWs in other 
countries who are authorized to initiate clients on DMPA (e.g., Afghanistan, Nepal, Madagascar, Uganda, 
Kenya). LHVs receive two years of training, and upon completion, are issued a diploma by the Pakistan 
Nursing Council (PNC). In terms of clinical competency, they are just below the level of midwife, which 
requires a third year of training. Lady Health Visitors work primarily in health facilities, but like LHWs, 
they also provide services in the community. Lady Health Visitors often supervise LHWs; unlike this lay 
cadre, they can provide injectables with no restrictions or need for monitoring or supervision.  
There are two other types of clinically-trained health care providers assigned to health facilities who are 
essentially equivalent to LHVs: Family Welfare Counselors (FWCs) and Family Welfare Workers (FWWs) 


 
 
 
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Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
who provide all FP methods except for tubal ligations. Henceforth, these providers will be subsumed 
under and referred to as LHVs for the purpose of simplicity.  
There is no national policy or strategy for community-based access to injectable contraception (CBA2I) in 
Pakistan. However, the PNC curriculum for LHWs includes training for administration of follow-up doses 
of intramuscular (IM) injectable contraception in the community, and they are allowed to do so without 
monitoring or supervision. Thus, the key and missing element for LHWs is evidence that they can screen 
and counsel first-time users of Depo Provera (DMPA) as proficiently as LHVs. Some LHWs have already 
demonstrated proficiency in injection technique for DMPA IM and many also provide vaccinations in 
their communities, which is the basis for allowing LHWs to resupply DMPA injections (M. Villanueva & F. 
Midhet, personal communication, December 19, 2016). 
National advocacy efforts to develop a strategy for CBA2I are ongoing and there is widespread support 
amongst the government, implementing partners, and donors. In 2014, a policy roundtable meeting on 
“Increasing Access to Family Planning through Task Sharing” was hosted by Marie Stopes and led by the 
Population Welfare Department. The focus of the meeting was to discuss options for addressing the 
high unmet need for FP and to develop policy recommendations and a way forward, including updating 
pre- and in-service curricula and training. There have also been policy level discussions at the 
community level in the Punjab and Sindh provinces on task sharing the administration of the first dose 
of Depo Provera IM.  There is agreement among stakeholders that a comparative study is valuable and 
timely, particularly for assurance on feasibility. Thus, the study is seen as essential to taking action.  With 
evidence, support can be focused on preparations for uptake in new areas and with new partners (for 
example, BMGF is launching a new program where task shifting injectables might be added to their 
approach).    
The Government of Sindh province has expressed interest in moving forward with this CBA2I action 
following positive results from targeted research. There is also interest in introducing Pfizer’s 
subcutaneous form of Depo Provera, Sayana Press® (SP) in Pakistan, which could simplify administration 
of injectable contraceptives—whether by LHWs or self-administration. As such, an SP arm will be 
included in the trial, which will be facilitated by relevant training of LHWs and LHVs by Jhpiego and 
stocks provided by a special USAID procurement, as the registration process for SP is ongoing. A 
successful RCT comparing the performance of LHWs and LHVs on first-dose initiation of Depo Provera IM 
(DMPA IM) and (SP) would facilitate efforts to expand CBA2I in Pakistan, and in turn improve access to 
family planning services for a potentially large number of underserved women. 
 
II. 
Objectives and Outcomes 
The overall goal of the trial is to provide high-level evidence that lay or community health workers can 
safely and effectively screen and initiate women who choose to use injectable contraceptives. The 
primary objective is: 


 
 
 
4 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
To assess whether the community health worker cadre, Lady Health Workers (LHWs) in Pakistan 
can screen and initiate women on intramuscular and subcutaneous Depo Provera injections as 
safely and effectively as their clinically-trained counterparts, Lady Health Visitors (LHVs).  
Although LHWs are already allowed to provide follow-up doses in the community, this RCT will focus on 
the comparison of safety and effectiveness of screening, counseling and first-time administration of 
DMPA IM and SP. Rather than focusing on determining whether services are better provided by one of 
the two health worker cadres, we want to determine if LHWs can perform just as well as the more 
experienced LHVs. Therefore, the trial will be powered specifically to detect non-inferiority (i.e., no 
difference) within a tolerance margin in the performance of LHWs compared to LHVs with regard to 
screening--the procedure that determines a woman’s eligibility to receive DMPA. We consider the 
assessment of the screening for DMPA use as the primary outcome of interest for addressing the 
primary objective. However, in addition to screening, metrics for counseling and administration of 
DMPA will constitute the endpoints for the primary objective described below:  
• 
Proportion of Lady Health Workers and Lady Health Visitors that appropriately screen women 
for DMPA use; 
• 
Proportion of Lady Health Worker and Lady Health Visitor clients that report discussion with 
their respective providers on side effects, danger signs, advantages and disadvantages of DMPA 
use;  
• 
Proportion of Lady Health Workers and Lady Health Visitors that demonstrate appropriate 
injection technique 
• 
Proportion of Lady Health Workers and Lady Health Visitors that report needle stick injuries; 
• 
Proportion of Lady Health Workers that properly maintains a client (re)injection log.  
Details on analysis of these endpoints will be provided in a separate data analysis plan.  
The secondary objective is: 
To assess whether DMPA clients of Lady Health Workers and Lady Health Visitors are equally 
satisfied with their respective providers and the family planning services they provide. 
 
The endpoints will be measures of satisfaction and quality reported by clients of LHWs and LHVs, such 
as: 
• 
Satisfaction with the method and its delivery (IM and SP); 
• 
Satisfaction with the services received from the provider; 
• 
Reports of client ability to speak freely and ask questions of provider; 
• 
Reports of friendly and respectful behavior toward client. 
 
 


 
 
 
5 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
 
III. 
Methodology 
Overview 
This will be a randomized controlled trial conducted in Sindh Province, Pakistan, using quantitative 
methods. Third-party, independent data collectors will be trained to perform onsite observations of 
screening and counseling of first-time DMPA clients performed by LHWs and LHVs in health facilities. 
Another health facility provider--blinded to the LHW or LHV who provided the initial screening--will 
verify client eligibility to use DMPA through their own client interview. If the independent screener 
deems the client eligible to receive DMPA, then the same provider who earlier screened and counseled 
her on the method will administer the injectable to her. Clients will also be randomized to receive DMPA 
IM or SP to prevent selection biases between these groups. However, comparisons between these 
injection techniques will only be considered exploratory, focusing instead on acceptability of and 
satisfaction with the method as reported by clients. 
Survey interviews with participating LHWs and LHVs will be conducted four to six months after trial 
initiation to obtain their feedback on providing DMPA IM and SP and attitudes towards LHW-initiation of 
injectables.  
The study is limited to participating LHWs, LHVs and to their clients who voluntarily and independently 
accept DMPA as their contraceptive method before study recruitment is initiated.  
 
Study setting and site selection 
Sindh Province, Pakistan was selected for this trial, because the Government of Sindh expressed interest 
in expanding community-based injectable provision. On a national scale, the Ministry of National Health 
Services, Regulation and Coordination is also receptive to CBA2I. Currently, LHWs in 17 of Sindh’s 23 
districts have been trained to provide follow-up injections of DMPA IM. A subset of LHWs who are 
actively providing services in these 17 districts will be selected to participate in the trial, which will 
ensure that experienced and competent lay health workers are trained to initiate clients on DMPA IM or 
SP.  
As family planning is widely-accepted–including with both religious and community leaders--opposition 
to the study is expected to be little to none. As such, community engagement will primarily include 
reaching out to existing structures such as active community-level health committees to inform them of 
and enlist support for the study. The relevant community health committees will be provided with 
information about the study and potential outcomes. In keeping with their role in the community, the 
committees will be encouraged and supported to cascade the announcement and ongoing sharing of 
information about the study launch, progress, and opportunities to participate. Community health 
committees will also be consulted to align launching the study with other messaging and events in the 
community which may impact awareness and interest in the study and availability of LHW provision of 
DMPA. If needed, deeper engagement with community health committees will be considered to boost 


 
 
 
6 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
awareness of the study and services available to qualified FP clients. This can be accomplished through 
monthly Community Support Group meetings designed to raise awareness about various maternal, new 
born, child health (MNCH) and family planning topics that LHWs discuss with women’s groups in their 
catchment areas. 
In this trial, health facilities (and their associated catchment areas) will be selected to allow for 
representation of rural and urban districts. Other criteria including moderate to high client volume, as 
well as practical considerations such as the implementation of fieldwork and randomization of LHWs or 
LHVs to provide DMPA services will be considered.  
Ten (10) health facilities will be selected from two districts in Sindh: Karachi and Thatta. Within those 
districts, health facilities in urban areas of Karachi and rural areas of Thatta will be approached to 
participate in the trial. The health facilities will be selected based on 1) the number of DMPA acceptors; 
2) availability of both LHVs and LHWs; and 3) logistical factors. Table 1 provides a proposed sample of 
study sites with DMPA client volume from the most recent month of available data. Final selection of 
districts and health facilities within them will be determined in collaboration with in-country partners, 
AKU and Jhpiego as more information on the distribution of LHWs and LHVs and client volume in Sindh 
becomes available. The sample, including the number of districts or the number of health facilities and 
their distribution may be adjusted based on this information. For example, we may add another rural 
district if sufficient numbers cannot be found that meet criteria for LHW experience, current status (i.e., 
active, not active) or the health facility’s ability or willingness to participate in the trial. Alternatively, 
more sites may be added within the same districts if client volume or health provider interest in trial 
participation is low.  
 
Table 1. Proposed health facilities and most recent DMPA client volume data 
Facility name 
District (location) 
Client volume in most recent 
month available of new and 
continuing injectable 
clients* 
RHS-A Center, SG Hospital Saudabad 
Karachi (urban) 
30 
FWC, SG Hospital Korangi 5 
Karachi (urban) 
125 
FWC-Shah Faisal Colony No. 1, KMS MCH 
Center 
Karachi (urban) 
82 
FWC Korangi 33-C, BHU Korangi 33-C 
Karachi (urban) 
73 
RHS-A Center, SG Hospital Ibrahim Hyderi 
Karachi (urban) 
67 
RHS-A Center, DHQ Hospital Makli 
Thatta (rural) 
32 
RSH-A Center, THQ Hospital Mirpur Sakro 
Thatta (rural) 
19 
Rural Health Center, Jherruk 
Thatta (rural) 
01 
RHS-A Center, THQ Hospital Sujawal 
Thatta (rural) 
38 
RHS-A Center, THQ Hospital Mirpur Bathoro 
Thatta (rural) 
16 
     *Data received 2/20/2017 
1 It is anticipated that this proposed study site will have sufficient clients during the data collection period.  


 
 
 
7 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
Target groups  
The three target groups in this RCT are LHWs, LHVs and DMPA clients. All women in these target groups 
will be at least 18 years of age.  
Lady Health Workers 
Selections will be based on LHW affiliation to the 10 health facilities in Sindh chosen to take part in the 
trial. Jhpiego will make the final selection of LHWs to be trained and to participate in the trial, which will 
be based on the following criteria: 
• 
Already trained to provide follow-up DMPA IM injections in their community; 
• 
Currently providing services in their community 
• 
Willingness and ability to participate in the trial 
Jhpiego will develop relevant materials and tools to carry out the training of LHWs to screen and counsel 
first-time DMPA users—both IM and SP acceptors. LHWs will also be trained, or if already experienced in 
this area, given a refresher on maintaining DMPA client records and re-injection logs—adapting existing 
Pakistani forms if necessary. Jhpiego’s training materials will be reviewed with the study team to ensure 
that the content is aligned with study objectives and procedures. 
Lady Health Visitors 
LHVs assigned to health facilities that correspond to the catchment areas of these LHWs, and who may 
in the normal course of their duties serve as their supervisors, will be eligible.  
Study logistics, resources and need will determine if LHVs should be included in trainings for DMPA IM, 
but they will be required to attend trainings on SP, as that method will be new to both health cadres. It 
is particularly important that LHVs be trained on SP along with LHWs, not only to ensure consistency in 
training and knowledge for both cadres, but also to enable LHVs’ supervisory obligations to their charges 
providing SP. Jhpiego will certify that once trained, LHWs and LHVs are proficient in screening, 
counseling and administration of both forms of DMPA prior to interacting with DMPA clients. 
Screening and counseling on the use of either type of DMPA has been simplified by WHO’s decision to 
employ the same medical eligibility requirements for both IM and SP formulations and to harmonize 
recommendations for the re-injection schedule and grace period (i.e., 2 weeks before the re-injection 
date or as late as 4 weeks after). Therefore, the only difference in service delivery will be the injection 
technique for DMPA IM and SP, as all other elements of method provision remain the same.  
LHWs and LHVs selected to participate in the trial should not be the “cream of the crop”. To reflect the 
real-world context outside a trial setting, any provider who successfully completes Jhpiego’s training 
should be eligible to participate in the trial. Consent will be sought from LHWs and LHVs to observe their 
interactions with DMPA clients, including the provision of services, as well as to be interviewed by study 
staff. 
 
 


 
 
 
8 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
DMPA acceptors 
Family planning clients provide the basis for assessment of LHW and LHV service provision. Thus, the 
eligibility criteria for family planning clients of LHWs and LHVs are: 
• 
Women who select DMPA as their contraceptive method for the first-time or after more than a 
six-month hiatus from the method; 
• 
Women of reproductive age (18 to 49) who can legally consent to receive reproductive health 
services and participate in research studies in the Pakistani context; 
• 
Women who consent to provision of DMPA services from LHWs or LHVs trained for the RCT; 
• 
Women who provide consent to be observed and interviewed by independent data collectors 
during the trial. 
Sample size 
We require a minimum of 342 DMPA clients randomized to receive care from either the LHV or an LHW 
(1:1 allocation) for 90% power and 5% significance level to test the non-inferiority hypothesis that LHWs 
can screen potential DMPA clients for method initiation just as adequately as LHVs with a non-inferiority 
margin of 7.5%, assuming that both LHVs and LHWs perform at a 95% success rate. In Pakistan, there is 
usually at least one LHV assigned to a health facility and many more LHWs affiliated with and under the 
supervision of resident LHVs. Therefore, we will use a 3 to 1 ratio of LHWs to LHVs at each health facility 
in the trial. The three LHWs will be placed on rotation to cover a three-month enrollment and data 
collection period in the health facility. Rotations among the three LHWs will be based on their individual 
availability and schedules; not on their perceived competencies or the preference of facility staff.  
In order to meet the desired sample size from LHWs and LHVs, we will select 10 health facilities that 
provide the most DMPA in Karachi and Thatta districts. These facilities will be distributed between rural 
and urban areas.  For logistical reasons, we plan to obtain the full target sample size of 342 DMPA 
initiators from the urban health facilities to ensure that adequate analyses can be done with this group. 
We will recruit additional participants from rural facilities to help assess possible differences in 
performance between LHVs and LHWs in rural and urban areas. Although, we don’t expect these 
differences to exist, the additional sample size will help us to assess whether differences may be likely to 
exist. If we can be comfortable that providers in rural and urban areas perform in similar manner, the 
overall sample size for the analysis may be pooled for an increase in power. Please note, however, that 
the additional sample size from rural areas will not be adequate for separate analyses by location or to 
assess rural and urban differences statistically. Rural facilities will likely provide a much lower number of 
DMPA acceptors in the three-month data collection period, but they will each be selected for their 
ability to enroll at least 20 new acceptors in that period of time. We will then expect to enroll 
approximately 100 DMPA acceptors from the rural facilities in the recruitment period for an overall total 
sample size of approximately 442 for this study.  
Given the relationship between LHWs and LHVs within clinics, we plan to account for the correlations of 
participant outcomes within providers and providers within clinics in the analysis. We expect that some 
of these correlations would lead to decreases in power, others to lead to increases in power for within 


 
 
 
9 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
clinic comparisons. Power calculations were not adjusted for these potential correlations as the net 
effect on power may be offset with each other.  
Please note that the screening outcome is not affected by the injection technique used, so power 
calculations focus on the overall comparison between LHV and LHW on the primary outcome. 
Furthermore, comparisons regarding injection techniques will be considered exploratory. 
 
Study procedures 
Data collection instruments 
FHI 360 Headquarters (HQ) staff will develop two survey questionnaires and three observation checklists 
for screening and counseling first-time DMPA acceptors. One questionnaire—an exit interview-- will be 
administered to DMPA clients, and the other, to LHWs and LHVs four to six months after initiation of the 
trial. Interviews with LHWs will be conducted during one of their routine visits to the health facility for 
resupply and supervision. LHWs will also be asked to present their family planning records at that time 
to determine if they properly maintain their injection and re-injection log books. Questions specific to 
LHWs and to LHVs will be arranged in separate sections of the instrument with appropriate skip 
patterns. 
Three observation checklists will be developed for screening and counseling DMPA users. Independent 
observers will document screening and counseling procedures employed by LHWs and LHVs on one 
checklist, while the other two checklists will document injection technique separately for DMPA IM and 
SP. 
Questionnaires 
The questionnaire items in the client exit interview instrument will focus on the following domains: 
• 
Sociodemographic characteristics 
• 
Experiences using contraceptive methods 
• 
Factors in her decision to use DMPA 
• 
Interaction with and information provided by LHW/LHV about DMPA 
• 
Satisfaction with her choice of DMPA as a contraceptive method (IM or SP) 
• 
Satisfaction with LHW/LHV 
Questionnaire items in the LHW/LHV interview instrument will focus on: 
• 
Sociodemographic characteristics 
• 
Knowledge of DMPA use and provision 
• 
General experiences and satisfaction with providing DMPA services 
• 
Reports of needlestick injuries  
• 
Observations of LHW (re)-injection logs 
 


 
 
 
10 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
Observation checklists 
The first checklist will adapt the 15 screening items from FHI 360’s “Checklist for Screening Clients Who 
Want to Initiate DMPA” (Figure 2). It includes pregnancy checklist items that determine client eligibility 
for DMPA use in the absence of pregnancy tests. The pregnancy checklist has been endorsed by WHO, is 
a proven proxy for pregnancy tests17,18 and is indispensable in non-clinical settings. In addition, items 
that capture the presence or absence of counseling on DMPA use will be incorporated as a second part 
of this checklist instrument, such as: 
• 
Discussion of advantages and disadvantages of DMPA use 
• 
Danger signs of DMPA use 
• 
Side effects and management of DMPA 
The remaining two checklists will separately assess LHW and LHV injection technique for DMPA IM and 
SP. The content of the checklists will be adapted from instruments developed for previous task sharing 
studies of injectable contraception and from PATH’s Sayana Press® training materials. 
All three checklists will be modified to capture the information from the point of view of the observer. 
That is, RAs will be asked to: 1) record if the LHW/LHV uses a physical checklist during screening and 
counseling; 2) make note of the questions asked and the responses given for the items on the checklists; 
and 3) document LHW’s/LHV’s decision(s) in light of client responses. 
Pilot testing and recruitment procedures 
Before the trial is initiated, we will pilot test not only the client exit interview instrument, but also 
procedures associated with recruitment, consent, randomization, blinded assessment and verification of 
DMPA eligibility by the independent, clinically-trained staff member. The client interview instrument will 
be pilot tested to ensure that 1) the items are understandable to DMPA clients, 2) they elicit the 
intended information, and 3) research assistants (RAs) acquire real-world practice in administering the 
interviews. Recent and continuing DMPA clients who may be known to Jhpiego’s LHW and LHV trainees 
will be identified and asked to assist with pilot testing the instruments.  
Pilot testing study procedures will familiarize RAs and health facility staff with the order and logic of 
randomization and blinding to reduce the occurrence of procedural errors that may compromise the 
quality and reliability of the findings.  
The provider interview instrument will also be pilot tested to ensure that the intended information is 
gathered and that RAs acquire practice in its administration.  
Since pilot testing is solely for providing practice to research staff and to improve the comprehensibility 
of our materials, data collection instruments will be destroyed by AKU after the necessary information 
has been obtained. 
Observation checklists have already been vetted through use in previous studies. However, RAs will be 
thoroughly trained by AKU staff to accurately record their observations of screening, counseling and 
injection technique in a standardized manner. AKU staff will receive guidance and in-person technical 


 
 
 
11 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
assistance from the FHI 360 Project Leader on data quality, management and human subjects research 
ethics before the training of data collectors is performed in Pakistan.  
After the instruments have been pilot tested and vetted, AKU research staff will identify women who: 1) 
meet age, marital status and new DMPA user criteria, 2) independently present at the study site or are 
accompanied by an LHW, and 3) express a desire to use injectable contraception. AKU research staff will 
approach women at each study site, inviting those who self-identify as potential DMPA clients and meet 
eligibility criteria to participate in the trial. In low volume health facilities, all women will be approached; 
in a high-volume facility, such as a hospital, we will approach women based on a random number 
generator (e.g., every nth woman) to meet the desired sample size at each study site.   
This study involves the provision of Sayana Press®, the subcutaneous form of DMPA that would not 
otherwise be available outside the study context, but only women who voluntarily and independently 
accept injectable contraception before study recruitment and enrolment will be asked to participate in 
this trial. 
The trained RA posted at each study site will confirm eligibility to participate in the study and obtain 
consent. The RA will explain to potential participants that participation in the study involves being 
randomized to receive services from an LHV or an LHW and either DMPA IM or SP; being observed 
during service delivery at the facility; and being interviewed right after completing her visit at the 
facility. Thus, the RA will obtain consent for the following: 
• 
Willingness to be randomized to provider and DMPA type 
• 
Observation of screening and counseling for DMPA (identical procedure for IM and SP); 
• 
Observation of first-time administration of either DMPA IM or SP (disparate procedures for the 
two); 
• 
Exit interview right after she receives very first dose of DMPA and before she leaves the health 
facility. 
With regard to providers, all LHVs will be interviewed, but only LHWs who provide DMPA services to at 
least nine new DMPA clients will be interviewed by RAs. With a 3:1 ratio of LHWs to LHVs, LHWs placed 
on rotation during the data collection period with approximately 34 clients being randomly assigned to 
LHWs per facilitya, it is possible that not all three LHWs participating in the trial will interact with at least 
nine DMPA clients. The threshold of nine DMPA clients served will ensure that LHWs interviewed obtain 
sufficient experience to share their perspectives on providing DMPA to new users. In order to interview 
some LHWs from rural sites, the quota will be lowered to include those who provided services to at least 
four new DMPA clients. 
Randomization procedures 
A randomization manager from FHI 360, who is not otherwise involved in the study, will prepare a 
computerized randomization list using permuted blocks before the start of the study. These envelopes 
                                                          
a A total of 342 DMPA acceptors will be distributed among the 5 health facilities in urban Karachi district. On average, about 68 
acceptors will be recruited per facility of which half will be assigned to LHWs. 


 
 
 
12 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
will be given to the local PI at AKU who will distribute the envelopes to RAs assigned to study health 
facilities. These RAs will open the randomization envelopes and inform LHWs or LHVs when they have 
been selected to provide DMPA services (screening, counseling) and which form of DMPA (IM or SP) 
they will provide after the independent third party verifies the client’s eligibility for DMPA use. 
Women will be randomized in a 1:1 ratio to proceed with DMPA screening by an LHV or LHW. After the 
independent staff member confirms the client’s eligibility to use DMPA, an identical randomization 
procedure will be performed to randomize women to receive either DMPA IM or SP. The master 
randomization list will be maintained at FHI 360 and will not be available to study staff. 
Randomization groups will be concealed in sequentially numbered, sealed opaque envelopes (SNOSE).  
We will instruct study staff never to open an envelope until the participant has given consent to 
participate in the study, is found to be eligible for the study, and is present for DMPA screening and the 
subsequent administration of the injectable. These envelopes will be provided to AKU in advance of trial 
implementation. The opened randomization envelopes will be retained as source documents and will be 
kept under secure and restricted access to protect the confidentiality of the participants. 
This is an open-label study – neither study staff nor participants will be blinded to study treatment arms 
after the point of randomization. Nonetheless, strict policies will be in place to preserve randomization 
integrity. Randomization documentation will be stored in a secure location. Data recording, assessment 
of the primary and secondary study outcomes, and other assessments, such as DMPA eligibility 
assessment by independent facility staff, will be blinded to treatment arm where possible. The FHI 360 
lead statistician and data analysts will perform a blinded review of the data to make final statistical 
decisions that could affect the comparison of the primary and secondary outcomes before fully 
unblinding the data for final analyses. Details of the analysis processes will be described in the detailed 
analysis plan. 
Screening, counseling and DMPA administration will all be performed by the same LHW or LHV 
randomized to provide services to that client. The receipt of DMPA IM or SP is being randomized to 
avoid an imbalance of DMPA type that could occur if clients are given the choice between the two 
delivery systems. Similarly, provider bias/preference for one form or the other of DMPA could result in 
the same. The following graphic describes the procedures, including randomization, to be adopted in 
this trial. 
 
 


 
 
 
13 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
 
 
 
 
 
 
 
 
 
Client Opting for the First Dose of DMPA Injection 
Randomization of clients for Screening, Counseling 
 
LHW 
 
LHV 
1st 
Observation 
1st 
Observation 
Gold Standard: Screening of the client by independent clinic staff 
Client Eligible for 1st dose 
Client not Eligible for 1st dose 
LHW or LHV from 
randomization above 
Advise/counsel for other FP 
methods 
DMPA Intramuscular 
SP (Sayana Press) 
2nd 
Observation 
2nd 
Observation 
Randomization of clients for DMPA type 


 
 
 
14 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
Data collection procedures 
Observation of screening and counseling 
After the DMPA client has provided informed consent and been randomized to see an LHW or an LHV, 
the RA posted at the study site will observe the screening and counseling interaction between the 
LHW/LHV and client. The RA will request that the interaction be conducted in accordance with the 
health facility’s privacy policy and with the normal procedure for client-provider interaction. As such, we 
are currently unable to specify a range of time in which these observations will be performed.   
The RA will first record observations using the first part of the checklist devoted to screening for client 
eligibility. If the LHW/LHV deems the client eligible for DMPA, then the RA will record whether or not the 
LHW/LHV proceeded to deliver key counseling elements of DMPA use to the client. All data will be 
recorded via pen and paper to be later entered into an electronic database.  
After the client has been counseled, the clinic staff assigned at that study site to provide support to the 
trial will verify that the client is indeed eligible to receive DMPA. The staff member will serve as the 
independent gold standard for LHW and LHV performance. If s/he confirms that the client is eligible for 
DMPA use, the client will then receive DMPA subcutaneously or via an intramuscular injection from the 
same LHW or LHV who earlier screened and counseled her. If the staff member determines that the 
woman is not eligible for DMPA use, she will be offered another method and released from participation 
in the trial. The LHV/LHW who incorrectly deemed the client eligible for DMPA will not be penalized and 
the event will be treated and utilized as a learning experience.  
Client exit interview 
After receipt of her first dose of DMPA, the RA will conduct a brief interview with the client before she 
leaves the health facility, at a designated area in or within 500 feet of the site that provides audio 
privacy. The interview is expected to take between 10 and 15 minutes. 
LHW/LHV interview 
About four to six months after trial initiation, some participating LHWs and all LHVs will be asked for 
their permission (via informed consent) to be interviewed by an RA. By that time, they would have all 
provided initial and follow-up injections to their DMPA clients and should be able to describe their 
experiences. LHVs and LHWs will be interviewed at their assigned study sites.  
As part of the interview process for LHWs only, the RA will be ask in advance of the meeting to bring 
their DMPA client materials with them. The RA will examine DMPA client records to verify that injection 
and re-injection dates are being recorded appropriately. Thus, as one of the objectives of the study, we 
will ascertain whether or not LHWs diligently record the dates of service for DMPA clients, how many 
are first-time or repeat DMPA clients, and if re-injection dates were scheduled for all of them. For LHWs 
who do not bring their logbook with them to the interview, a second and final session will be scheduled 
to capture that information. No additional attempts will be made gather that information from the LHW 
and the data will be considered missing for that LHW. 


 
 
 
15 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
 
IV. 
Data management and analysis plan 
Coordination of activities 
FHI 360 will contract with AKU to implement the trial in Sindh province. AKU will assign (or hire) and 
train personnel to observe and record the interactions between DMPA clients and LHWs/LHVs and to 
conduct the interviews as indicated. AKU personnel will also participate in the pilot testing of data 
collection instruments and recommend modifications if necessary before the trial is initiated. AKU will 
also ensure that the importance of randomization is stressed to health facility staff and strictly observed 
at all study sites.  
FHI 360 and AKU will work together to obtain institutional review board (IRB) approval from their 
respective organizations, the Protection of Human Subjects Committee (PHSC) and the Aga Khan 
University Ethics Review Committee. AKU will also facilitate IRB approval from Pakistan’s National 
Bioethics Committee. In conjunction with Jhpiego, AKU will develop and maintain relations throughout 
the trial with management and staff at study sites. Nurturing a relationship with health facility staff will 
help with tracking the intervention process and gaining input and insights for scale-up, which are 
described in the Research Utilization section below. 
Data management 
FHI 360 and AKU will use software compatible for data entry, management and analysis across the 
organizations. AKU will create database shells and capture interview and observation data via paper and 
pen instrumentation. Each participant will be assigned a unique identifier that will facilitate data entry 
and management, as well as ensure confidentiality. 
 
FHI 360 will review database structures and documentation and verify the accuracy and completeness of 
the database shells for interviews and observations before AKU begins data entry. AKU will use a system 
of double data entry and frequency checks to minimize data entry errors for all interview instruments. A 
study coordinator at AKU will oversee day-to-day management of the trial, including cleaning and 
verification of data on an ongoing basis. The study coordinator will also communicate regularly with the 
project leader at FHI 360 to provide updates and resolve any challenges that may arise during the course 
of the trial. Clean databases will be sent to FHI 360 for verification and analysis according to the timeline 
for those deliverables. 
 
During all phases of data collection, entry, cleaning and verification, access to hard copy and electronic 
data will only be granted to research staff at AKU and FHI 360. Any hard copies of interviews, 
observation checklists and other materials containing study data will be stored in a locked file cabinet at 
AKU. Informed consent forms will be stored in a separate locked drawer or cabinet. Electronic data will 
be stored in password-protected files. Only staff working on the study will have access to the cabinets 
and electronic files. Upon completion of the trial, all stored materials will be destroyed at AKU. 
However, no records will be destroyed without permission from the FHI 360 project leader.  


 
 
 
16 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
 
Data Monitoring 
Since AKU will conduct ongoing data entry and management, data monitoring will also be continuous. 
FHI 360’s project leader will work closely with AKU to oversee the scope of the work. Management of 
the trial by AKU will include day-to-day supervision of RAs, including quality checks for completeness 
and accuracy of interview and observation checklist data shortly after they have been completed. Staff 
from AKU will be responsible for identifying, documenting, mitigating and reporting protocol violations 
as well as serious adverse events related to the provision of DMPA. 
Data analysis 
We plan to compare a series of indicators of the performance of LHWs compared to LHVs in the 
provision of injectable contraception services. Our primary outcome is related to the screening process. 
We will test the non-inferiority hypothesis that LHWs can screen potential DMPA clients for method 
initiation just as adequately as LHVs with a non-inferiority margin of 7.5%. Given the relationship 
between LHWs and LHVs within clinics, we plan to use a generalized mixed model using a logit link to 
account for the correlations of participant outcomes within providers and providers within clinics. 
Random effects will be included for clinics and providers within clinic. The non-inferiority test will be 
conducted at a 5% significance level. A similar approach will be used to compare other performance 
outcomes. No covariate adjustments are planned for the primary analyses. However, these may be 
included for exploratory analyses. If any, these will be specified in the detailed analysis plan prior to data 
analysis. Other comparisons between groups will be primarily descriptive to explore the differences in 
the provision of DMPA services by each cadre of provider. Similarly, comparisons between injection 
techniques will be primarily descriptive and exploratory. 
 
V. 
Research utilization and dissemination activities 
A detailed Research Utilization (RU) Plan, including plans for scale-up and proposed RU activity timeline, 
will be jointly developed and agreed upon with partners after approvals have been obtained for this 
study. FHI 360 will coordinate with Jhpiego to identify the major elements of the RU Plan (Findings 
products; End users; Dissemination partners; Communication; Evaluation; Work plan) and responsible 
party.  
This study methodically incorporates the research utilization principles and activities needed to support 
the application of evidence to policies and programs and increase the return on investments in research. 
Findings from this study will inform policy dialogue across provinces and at the federal level and, if 
findings prove positive, help position the practice of LHW-provision of DMPA for future scale-up. 
However, the study results cannot make an impact unless decision-makers understand and use that 
evidence to inform policy and program design. For that to occur, research findings must be properly 
communicated — at relevant moments, to particular audiences, and in ways that potential users can 
comprehend.19  


 
 
 
17 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
Deliberate and strategic research utilization activities will be carried out for each of three phases of the 
research utilization process: (1) research conceptualization stage (already realized with input from 
WHO), which includes “beginning with the end in mind”, stakeholder analysis and consultation, 
including potential future implementers, and planning for later analysis of scale up costs; (2) 
implementation stage, which prioritizes continuous stakeholder engagement and intervention process 
documentation; and (3) dissemination and utilization stage, including stakeholder workshop, research 
summaries, reports and manuscripts, and development of a scale-up strategy, as appropriate.  
On a quarterly basis, the study partners (MOH, Jhpiego, AKU, and FHI 360, and local community 
representatives) will convene standing meetings and review implementation progress and study data 
and guide the project throughout its implementation. The intervention process will be documented 
throughout implementation in order to help interpret findings later and to inform potential future 
expansion of the program.  Local community representatives will also participate in the meetings. Key 
influencers and decision makers at this level include the Department of Health Provincial Chief Minister, 
LHW Program Managers, and Community Health Committees. This degree of ownership by stakeholders 
in the intervention and their participation in its development will help position it for future scale-up and 
replication, if research results are positive. 
Sustainability and capacity building will be considered at all times during preparation and 
implementation phases of the study. Existing local materials (e.g., training curricula and M&E tools) will 
be adapted wherever feasible.  
At the conclusion of the study, results will be disseminated locally at a stakeholder workshop. 
Stakeholders will be invited to discuss the research findings and the implications for policy and practice. 
They may also be encouraged to participate in the development of a program scale-up strategy, if 
appropriate.  
The findings of this RCT are uniquely poised to contribute to a larger global body of evidence around 
task sharing best practices. Efforts to disseminate study data and lessons learned more widely after the 
conclusion of the project may include technical and program briefs, articles submitted for publication in 
peer-reviewed journals, and conference presentations. 
 
VI. 
Protection of human subjects 
Ethics review and certification 
FHI 360’s Office of International Research Ethics (OIRE) and Aga Khan University’s ethics review 
committee will initially review and approve all study materials. Pilot testing of data collection forms may 
occasion changes in the content, flow and number of questionnaire items. However, we anticipate that 
these changes would not be at variance with the topics approved in the initial review of study materials. 
Any changes made to the data collection forms that are beyond the topics described in the protocol will 
be resubmitted for review and approval prior to use. Copies of final versions of all the data collection 
instruments used in the field will be submitted to OIRE to be housed as part of the research record. 


 
 
 
18 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
Data collectors will receive training in the ethical conduct of research, which will be overseen by AKU 
staff using FHI 360’s Research Ethics Training Curriculum. Interviewers will be particularly sensitized to 
the importance of properly obtaining consent and ensuring and maintaining confidentiality of the study 
participants. 
Informed consent process 
LHWs and LHVs affiliated with selected study sites and trained by Jhpiego on the use of DMPA IM and SP 
will be asked to participate voluntarily in the trial. RAs will describe the study, their roles and 
responsibilities during the trial and provide them with a copy of the informed consent form, which will 
describe the risks and benefits of participation. All LHWs and LHVs will be asked to provide written 
consent. They will be told that their interactions with DMPA acceptors will be observed and recorded 
(using pen and paper) and that they will be interviewed about their experiences screening, counseling 
and administering DMPA to clients. LHWs and LHVs will be told that they will not be penalized if 
checklist observations reveal shortcomings in their performance. Instead, it will be recommended that 
they review the case with a qualified facility staff member for remediation. Once they agree to 
participate in the trial, they can stop their participation at any time. During the interview process, they 
can refuse to answer particular questions or can stop the interview at any time. They will be interviewed 
in a location that affords audio privacy and their responses will be kept confidential. The data from 
interviews and observations will be reported in the aggregate to prevent the identification of individual 
LHW and LHV performance. They will also be told that their names will not appear in any reports. 
As in the case of LHWs and LHVs, all participating DMPA acceptors will be adult women of reproductive 
age (18 to 49), almost always married, who can legally consent to participate in research studies. 
Moreover, it is practically unheard of that unmarried women seek family planning or reproductive 
health services. Nevertheless, we do not anticipate that any married study participants-LHW, LHV, or 
DMPA client, will be younger than 18 years of age. 
RAs will read informed consent forms to potential participants in the local language; women will be 
provided with a copy of the form so they may also read the consent documents themselves individually. 
All participants will be asked to provide written consent before data collectors proceed with 
observations of client-provider interaction, and subsequently, the client exit interview. RAs will sign the 
consent form to document that informed consent has been obtained.  
The informed consent form for DMPA acceptors will describe the risks and benefits of participating in 
the study. There is very low risk associated with participation, both because of the nature of the study 
(observations of client-provider interactions in health facilities, interview assessing service quality and 
satisfaction), because all participants will be informed that their responses will be kept in confidence 
and that they have the right to decline to be interviewed without fear that their refusal might affect the 
level or quality of services they receive at the facility. They will also be told that during the interview, 
they have the right to discontinue at any time or refuse to answer individual questions.  
A copy of the consent forms for both providers (LHWs, LHVs) and DMPA clients, with the name and 
contact information of the representative of AKU as well as the local IRB contact, will be offered to every 
participant.  


 
 
 
19 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
Risks and benefits 
The purpose of this research is to determine if the initiation of DMPA services can be safely shifted to 
the lay cadre, LHWs in Pakistan so that family planning services can become more accessible to women 
in rural and underserved areas. Sayana Press® will be used for the first time in Pakistan as a result of this 
trial, but the product has been vetted and approved for contraceptive use by the World Health 
Organization. This subcutaneous form of DMPA is currently available in many countries where providers, 
including community health workers administer the method to clients and where clients themselves 
self-inject.  As such, there are a few anticipated risks for participants enrolled in this study, because all 
instances of SP administration will be performed by trained LHWs and LHVs.  
Some LHWs/LHVs or DMPA clients may feel uncomfortable or embarrassed when asked questions about 
their personal experiences using FP methods. Participants will be told they do not have to answer any 
questions and they can stop participation at any time. Study staff will make every attempt to ensure a 
comfortable and secure environment in which to interact with participants. While staff will make every 
effort to protect individual participant’s privacy during data collection and confidentiality of the data 
collected, it is possible that participant’s involvement in interviews and observations could become 
known to others or others could learn something about the participants. There will be no identifying 
information on data collection instruments and datasets will be cleaned of potentially identifying 
information. The study team will take all measures to protect the identity of study participants and the 
confidentiality of their data.  
There is no direct benefit to participants for taking part in this research. However, the information they 
facilitate through observations or provide in interviews may be used to inform and improve FP services 
for women in Pakistan.   
Compensation 
As stipulated by government rules, LHWs (and as applicable, LHVs) will be provided with a daily 
allowance during the trial to reflect their execution of additional tasks. LHWs will also receive a 
transportation allowance for travel to study health facilities. No compensation will be offered to DMPA 
clients.  
Protection of privacy and confidentiality 
All interviews will be conducted in a private area in or within 500 feet of the health facility where the 
conversation will not be overheard. To ensure confidentiality, all participants will be assigned unique ID 
numbers. Names will not appear on any of the data collection instruments. Findings will be reported in 
the aggregate for both LHWs/LHVs and DMPA clients—limiting identification of individual participants. 
All study materials will be secured in dedicated locked cabinets/drawers or stored on password-
protected computers with access granted only to research staff for data management and analysis. 
For observations, if problems emerge during client interactions, a qualified facility staff member will be 
asked to intercede, take corrective measures and provide supportive supervision to the LHW/LHV as a 


 
 
 
20 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
learning experience. The LHW/LHV will not be penalized, and the data captured by the observer, pre-
intercession, will be entered in the study record and kept confidential. 
 


 
 
 
21 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
VII. 
Appendix 
Figure 1: WHO guidance on task sharing of family planning service delivery 
 
Source: WHO recommendations Optimizing health worker roles to improve access to key maternal and newborn 
www.optimizemnh.org  
 
 


 
 
 
22 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
Figure 2: Graphic presentation of observation checklist for screening
 


 
 
 
23 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
 
Figure 3: Timeline of trial activities 
Study Tasks 
Month 
1 
Month 
2 
Month 
3 
Month 
4 
Month 
5 
Month 
6 
Month 
7 
Month 
8 
Month 
9 
Month 
10 
Month 
11 
Month 
12 
In-house review of 
study materials 
X 
 
 
 
 
 
 
 
 
 
 
 
IRB (PHSC, AKU) review 
of study materials 
X 
X 
 
 
 
 
 
 
 
 
 
 
Local IRB(s) review of 
study materials 
 
X 
X 
 
 
 
 
 
 
 
 
 
SOW finalized with AKU  
 
 
X 
 
 
 
 
 
 
 
 
 
Study prep in field (local 
approvals, community 
engagement)  
 
 
X 
X 
 
 
 
 
 
 
 
 
Orient trained LHVs, 
select trained LHWs for 
rotation at study sites;  
 
 
 
X 
 
 
 
 
 
 
 
 
Train RAs; conduct pilot 
tests 
 
 
 
X 
 
 
 
 
 
 
 
 
Pilot-test trial 
procedures at study 
sites 
 
 
 
X 
 
 
 
 
 
 
 
 
Recruit DMPA clients; 
conduct observations, 
exit interviews   
 
 
 
X 
X 
 
 
 
 
 
 
 
Conduct interviews with 
LHVs and select LHWs 
 
 
 
 
 
 
 
X 
X 
 
 
 
Perform ongoing data 
entry, management and 
cleaning  
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Analyze and interpret 
data 
 
 
 
 
 
 
 
X 
X 
X 
 
 
Write-up trial results 
 
 
 
 
 
 
 
 
 
X 
X 
 
Disseminate trial results 
(in-country seminar, 
research brief, 
publications) 
 
 
 
 
 
 
 
 
 
 
X 
X 


 
 
 
24 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
Endnotes 
1 http://apps.who.int/iris/bitstream/10665/43821/1/9789241596312_eng.pdf 
 
2 http://www.psi.org/publication/task-sharing-to-increase-access-to-contraception-a-proven-strategy-that-makes-
a-difference/ 
 
3 Mbow FB, Ningue EAB, Diop N, Mané B, Ngouana R. 2015. “La délégation des tâches dans le domaine de la 
planification familiale au niveau communautaire dans les pays du Partenariat de Ouagadougou : Expériences et 
leçons apprises pour une mise en oeuvre effective – Présentation par pays”. Dakar: Population Council. 
 
4 Gordon-Maclean C, Nantayi LK, Quinn H, Ngo TD. 2014. Safety and acceptability of tubal ligation procedures 
performed by trained clinical officers in rural Uganda. International Journal of Gynecology and Obstetrics, 124: 34-
37.  
 
5 Duvall S, Thurston S, Weinberger M, Nuccio O, Fuchs-Montgomery N. 2014. Scaling up delivery of contraceptive 
implants in sub-Saharan Africa: Operational experiences of Marie Stopes International. Global Health: Science and 
Practice, 2(1): 72-92. 
 
6 http://www.popcouncil.org/uploads/pdfs/2014RH_GhanaTaskSharingPolicyBrief.pdf 
 
7 Asnake M, Tilahun Y. 2010. “Scaling up community-based service delivery of Implanon: the Integrated Family 
Health Program’s experience training health extension workers”. Addis Ababa, Ethiopia: Pathfinder International. 
 
8 Malarcher S, Meirik O, Lebetkin E, Shah I, ieler J, Stanback J. 2011. Provision of DMPA by community health 
workers: What the evidence shows. Contraception, 83: 495-503. 
 
9 Stanback J, ieler J, Shah I, Finger WR, et al. 2010. Community-based health workers can safely and effectively 
administer injectable contraceptives: Conclusions from a technical consultation. Contraception, 81:181-184. 
 
10 Prata N, Vahidnia F, Potts M, Dries-Daffner I. 2005. Revisiting community-based distribution programs: Are they 
still needed? Contraception, 72: 402-407. 
 
11 http://apps.who.int/iris/bitstream/10665/77764/1/9789241504843_eng.pdf?ua=1 
 
12 http://apps.who.int/iris/bitstream/10665/181041/1/9789241549264_eng.pdf?ua=1 
 
13 http://peersforprogress.org/wp-content/uploads/2013/09/20130923_pakistans_lady_health_workers.pdf 
14 National Institute of Population Studies (NIPS) [Pakistan] and ICF International. 2013. Pakistan Demographic and 
Health Survey 2012-13. Islamabad, Pakistan, and Calverton, Maryland, USA: NIPS and ICF International. 
 
15 http://2013-2014progress.familyplanning2020.org/A-Closer-Look-Pakistan 
 
16 http://ec2-54-210-230-186.compute-1.amazonaws.com/wp-content/uploads/2016/06/CIP-Sindh-03-15-16-final-
1.pdf 
 
 
                                                          


 
 
 
25 
Protocol: Comparative trial of DMPA administration in Pakistan 
Approved by AKU ERC 9/22/17; Approved by National Bioethics Committee, Pakistan 8/8/17 
Study #1035709, Version 3.0  
 
                                                                                                                                                                                           
17 Stanback J, Nanda K, Ramirez Y, Rountree W, Cameron SB. 2008. Validation of a job aid to rule out pregnancy 
among family planning clients in Nicaragua. Revista Panamericana de Salud Pública/Pan American Journal of Public 
Health, 23(2):116-118. 
 
18 Stanback J, Qureshi Z, Sekadde-Kigondu C, Gonzalez B, Nutley T. 1999. Checklist for ruling out pregnancy among 
family-planning clients in primary care. Lancet, 354(9178):566. 
 
19 Bennett G, Jessani N. The knowledge translation toolkit. Bridging the know-do gap: a resource for researchers. 
Sage India, IDRC; 2011. http://ajpp-online.org/resources/downloads/04-TheKnowledgeTranslationToolkit.pdf. 
 

SAP_001.pdf: 
 
Statistical Analysis Plan, Study #1035709 
Version 1.0 Last updated: August 15, 2018  
 
 
 
 
 
Page 1 
 
IRBNET# 1035709: A randomized controlled trial of safety and effectiveness of Depo Provera 
intramuscular and subcutaneous administration comparing lay Lady Health Workers with 
clinically-trained Lady Health Visitors in Pakistan 
STATISTICAL ANALYSIS PLAN 
This statistical analysis plan gives a detailed explanation of the data analysis summary included in the 
study protocol. 
I. 
Study Objectives 
The goal of this evaluation is to assess whether the community health worker cadre, Lady Health Workers 
(LHWs) in Pakistan can screen and initiate women on intramuscular (IM) and subcutaneous Depo Provera 
injections as safely and effectively as their clinically-trained counterparts, Lady Health Visitors (LHVs). 
Although LHWs are already allowed to provide follow-up doses in the community, this RCT will focus on 
the comparison of safety and effectiveness of screening, counseling and administration of DMPA IM and 
the subcutaneous injection, Sayana Press® (SP). 
The study’s primary outcomes are: 
• 
Proportion of Lady Health Workers and Lady Health Visitors that appropriately screen women for 
DMPA use; 
• 
Proportion of Lady Health Worker and Lady Health Visitor clients that report discussion with their 
respective providers on side effects, danger signs, advantages and disadvantages of DMPA use;  
• 
Proportion of Lady Health Workers and Lady Health Visitors that demonstrate appropriate 
injection technique 
• 
Proportion of Lady Health Workers and Lady Health Visitors that report needle stick injuries; 
• 
Proportion of Lady Health Workers that properly maintains a client (re)injection log. 
A secondary objective is to assess whether the clients of LHWs and LHVs are equally satisfied with their 
respective providers and the family planning services they provide. 
The study’s secondary outcomes are:  
• 
Satisfaction with the method; 
• 
Satisfaction with the services received from the provider; 
• 
Reports of client ability to speak freely and ask questions of provider; 
• 
Friendly and respectful behavior toward client. 
II. 
Study Design 
This study is a randomized controlled trial conducted in urban and rural health facilities in Sindh 
Province, Pakistan, using quantitative methods. The study is limited to participating LHWs, LHVs and to 
their clients who voluntarily and independently accept DMPA as their contraceptive method before 
study recruitment is initiated. Clients will be randomized to receive treatment from either an LHW or an 
LHV and will also be randomized to receive DMPA IM or SP to prevent selection biases between these 


 
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Page 2 
 
groups. However, comparisons between these injection techniques will only be considered exploratory, 
focusing instead on acceptability of and satisfaction with the method as reported by clients as well as 
provider knowledge and the latter’s comparisons of SP and DMPA IM. 
III. 
Target Population & Eligibility 
The target population for this study is Lady Health Workers and Lady Health Visitors trained to initiate 
intramuscular and subcutaneous Depo Provera use, as well as DMPA clients of trained Lady Health 
Workers and Lady Health Visitors. 
Eligibility criteria for the study populations are described in table 1. All participants must be at least 18 
years of age and consent to being observed and interviewed by study staff. 
Table 1: Eligibility criteria 
Lady Health Worker Criteria 
(n=30) 
Lady Health Visitor Criteria 
(n=10) 
DMPA acceptors 
(n=442) 
• 
Already trained to provide follow-
up DMPA IM injections in their 
community; 
• 
Currently providing services in 
their community 
• 
Willingness and ability to 
participate in the trial 
 
• 
Assigned to health facilities 
that correspond to the 
catchment areas of the 
LHWs 
• 
Willingness and ability to 
participate in the trial 
 
• 
Women who select 
DMPA as their 
contraceptive method 
for the first time or 
after more than a six-
month hiatus  
 
• 
Age 18 to 49 and able 
to legally consent to 
participate 
 
• 
Consent to provision 
of DMPA services 
from an LHV or a 
trained LHW. 
• 
Willingness and ability 
to participate in the 
trial 
IV. 
Sampling Design 
We require a minimum of 342 DMPA clients randomized to receive care from either the LHV or an LHW 
(1:1 allocation) for 90% power and 5% significance level to test the non-inferiority hypothesis that LHWs 
can screen potential DMPA clients for method initiation just as adequately as LHVs with a non-inferiority 
margin of 7.5%, assuming that both LHVs and LHWs perform at a 95% success rate. In Pakistan, there is 
usually at least one LHV assigned to a health facility and many more LHWs affiliated with and under the 
supervision of resident LHVs. Therefore, we will use a 3 to 1 ratio of LHWs to LHVs at each health facility 
in the trial.  


 
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For logistical reasons, we plan to obtain the full target sample size of 342 DMPA initiators from the 5 
urban health facilities in Karachi to ensure that adequate analyses can be done with this group. We will 
recruit additional participants (~100) from 5 rural facilities in Thatta to help assess possible differences 
in performance between LHVs and LHWs in rural and urban areas, but the expectation is that there will 
be no difference. LHWs undergo standardized training in Pakistan. If we can be comfortable that 
providers in rural and urban areas perform in similar manner, the overall sample size for the analysis 
may be pooled for an increase in power. The decision whether to pool the data or not will be made 
during the blind review of the data as described below.  
Given the relationship between LHWs and LHVs within clinics, we plan to account for the correlations of 
participant outcomes within providers and providers within clinics in the analysis. We expect that some 
of these correlations would lead to decreases in power and others to lead to increases in power for 
within clinic comparisons. Power calculations were not adjusted for these potential correlations as the 
net effect on power may be offset with each other.  
V. 
General Analytic Considerations 
A. Data Sources 
A.1 Client exit interview 
Client exit interviews measure the study’s secondary outcomes of client satisfaction with the method 
and provider. The exit interview also provides additional information related to appropriate screening 
such as discussion of side effects, warning/danger signs, advantages and disadvantages of DMPA use 
with clients. The client exit interview includes questions on the following domains: 
1. Sociodemographic characteristics 
2. Experiences using contraceptive methods 
3. Factors in her decision to use DMPA 
4. Interaction with and information provided by LHW/LHV about DMPA 
5. Satisfaction with her choice of DMPA as a contraceptive method (IM or SP) 
6. Satisfaction with LHW/LHV 
A.2 LHW/LHV interview 
Questionnaire items in the LHW/LHV interview instrument include: 
• 
Sociodemographic characteristics 
• 
Knowledge of DMPA use and provision 
• 
Comparisons between the properties/characteristics of SP and DMPA IM injections 
• 
General experiences and satisfaction with providing DMPA services 
• 
Reports of needlestick injuries  
• 
Observations of LHW (re)-injection logs 
A.3 Observation Checklists 
Three checklists adapted from existing instruments will be used to capture information on LHW and LHV 
services from the point of view of the observer. These are the source of the study’s primary outcome 
measures for appropriate screening and counseling as well as appropriate injection technique. 


 
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The first checklist will adapt the 15 screening items from FHI 360’s “Checklist for Screening Clients Who 
Want to Initiate DMPA” (Figure 1). In addition, items that capture the presence or absence of counseling 
on DMPA use will be incorporated as a second part of this checklist instrument, such as: 
• 
Discussion of advantages and disadvantages of DMPA use 
• 
Warning or danger signs of DMPA use 
• 
Side effects and management of DMPA 
The remaining two checklists separately assess LHW and LHV injection technique for DMPA IM and SP. 
The content of the checklists was adapted from instruments developed for previous task sharing studies 
of injectable contraception and from PATH’s Sayana Press® training materials. 
B. Data Management 
 
A trained RA will be posted at each study site to conduct observations of the screening and counseling 
interaction between the LHW/LHV and client, and to conduct a brief interview with the client before she 
leaves the health facility (i.e., the client exit interview). Nurses at each health facility will serve as the 
gold standard to which LHW and LHV screening will be compared. That is, screening outcomes are 
considered accurate and appropriate if they agree with the gold standard nurse’s assessment 
immediately following the LHV’s or LHW’s screening of DMPA acceptors. About four to six months after 
trial initiation, all participating LHWs and LHVs will be asked for their permission (via informed consent) 
to be interviewed by an RA at their assigned study sites. All data will be recorded via pen and paper and 
later entered into an electronic database.  
Data Cleaning 
The Department of Community Health Sciences, Aga Khan University (AKU), Pakistan, the local research 
agency, will create database shells. FHI 360 will review database structures and documentation prior to 
data entry. AKU will use a system of double data entry and frequency checks to minimize data entry 
errors for all interview instruments. A study coordinator at AKU will oversee day-to-day management of 
the trial. Clean databases will be sent to FHI 360’s data manager for verification according to the 
timeline for those deliverables. FHI 360’s data manager will provide access to the blinded data to the 
analysis team for blind review of the data and unblinded data for final analyses when the data analysis 
team is ready (see details below).  
 
No imputation of missing data will be performed. However, to decrease the number of cases when 
composite measures for observations of injection technique may be missing, where less than 15% of the 
items are missing among variables needed for deriving composite variables, we may decide to impute 
the mean of the non-missing items. Missing data will be noted in Table or Figure footnotes. Proportions 
and mean/median values will be calculated with missing data excluded from the denominator. 
 
During all phases of data collection, entry, cleaning and verification, access to hard copy and electronic 
data will only be granted to research staff at AKU and FHI 360. Hard copies of interviews, observation 
checklists and other materials containing study data will be stored in a locked file cabinet at AKU. 
Informed consent forms will be stored in a separate locked drawer or cabinet. Electronic data will be 


 
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stored in password-protected files. Only staff working on the study will have access to the cabinets and 
electronic files. Upon completion of the trial, all stored materials will be destroyed at AKU. However, no 
records will be destroyed without permission from the FHI 360 project leader.  
 
C. Definition of Variables 
 
Key primary outcomes will be calculated as follows. 
Screening for DMPA use  
There are 15 screening questions on the job aid that providers use to determine if a client is or is not a 
good candidate for DMPA or needs further evaluation before initiating DMPA. The provider makes a global 
decision of eligibility or ineligibility based on the job aid items and whether or not she would subsequently 
initiate the client on DMPA. The observer notes the provider’s decision whether to start the client on 
DMPA. This global decision (and not agreement on every screening item), is compared with the gold-
standard nurse’s assessment of client eligibility to generate the outcome variable for appropriate 
screening. Thus, the gold standard nurse’s overall assessment of eligibility is made after the provider’s as 
verification, and s/he is the final arbiter of eligibility. Thus, if the gold standard nurse determines that the 
client is eligible to use DMPA, the latter will receive the injectable regardless of the provider’s assessment. 
To avoid bias, the gold standard nurse is blinded to the type of provider who assessed the client 
beforehand. Whether or not they are deemed eligible to use DMPA as their chosen method, all clients will 
receive counseling appropriate to their circumstance.  
Counseling for DMPA use 
Appropriate counseling is a composite binary variable that will be calculated from observations of the 
discussion between the provider and client. If the provider spoke to the client about side effects, warning 
or danger signs, advantages, and disadvantages of DMPA, then the conditions are met for appropriate 
counseling (all conditions must be met for considering the counseling appropriate). If any is missing, the 
counseling is deemed inappropriate. These variables will also be presented separately in the descriptive 
analyses by type of provider (and urban/rural setting if the data are not pooled). 
Appropriate injection technique 
Appropriate injection technique is assessed using checklists for DMPA-IM and DMPA-SC previously 
developed and validated for this purpose. To meet the criteria for appropriate administration of the 
injection, the provider must complete 80% of the items on the checklist (i.e., at least 18 out of 22 for SP 
and at least 14 out of 17 for IM). 
D. Blind Data Review 
 
Even though the study is open labeled, the randomization was prepared by an independent 
randomization manager and data management is separated from the analysis team. Thus, the analysis 
team will initially be blinded to the group assignments. Unblinding of the analysis team will follow a 
three-step process: First, key decisions regarding the primary and secondary outcomes listed above will 


 
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be made blinded to study group assignment. These outcome variables will be constructed, checked for 
missing data, distributional anomalies or other problems, finalized and verified. Decisions about re-
categorization, transformation, missing data, and final variable definition will be completed after initial 
descriptive analysis and prior to further analysis for the specific objectives. Descriptive analysis of the 
outcomes will be done by facility and rural/urban designation. This check will also include a check of 
protocol violations, such as randomization errors (this review will be coordinated between the data 
manager and the randomization manager to maintain blinding of the analysis team) to decide if any data 
should be excluded from the analysis. Primary analysis will be conducted based on the intent to treat 
(ITT) approach where all participants randomized will be analyzed in the study group to which they were 
randomized. During blind review, decisions will be made regarding any modification to the ITT principle 
for primary analysis and whether a per protocol analysis will be conducted as secondary or sensitivity 
analysis. Second, once these key decisions have been made, the randomization manager will provide a 
participant list with blinded study arm assignments to the analysis team. A descriptive bivariate analysis 
will be done using blinded treatment assignments stratified by rural/urban designation to assess 
whether pooling the data will be appropriate. A decision whether further analysis will be pooled or not 
will be done at this time. Partial blinding will be maintained until statistical conclusions regarding the 
primary outcome (screening outcome) and primary analysis have been made and verified. This will be 
based on the pooled data or on the urban data only depending on the decision made in the prior step. 
The analysis team will be fully unblinded for all remaining analysis. 
E. Test Size and Confidence Levels 
 
The type I error for the non-inferiority test and other performance outcomes will be set at the two-sided 
α=0.05 significance level. 
VI. 
Analysis of Fieldwork Data 
An analysis of fieldwork data will be presented. This will include the number of DMPA acceptors 
approached, included, and randomized to LHW or LHV care.  
VII. Analysis of participant characteristics 
A descriptive summary of DMPA user, LHV, and LHW characteristics will be presented by urban and rural 
setting. DMPA client characteristics will include age, marital status, education, number of children, 
desire for more children, and birth spacing plans. Provider characteristics will include age, marital status, 
education, years of service, and years of DMPA experience. 
VIII. Analysis of Study Objectives 
We plan to compare a series of indicators of the performance of LHWs compared to LHVs in the 
provision of injectable contraception services. Our primary outcome, appropriate screening, is a binary 
variable comprised of the gold standard nurse’s assessment of client eligibility for DMPA compared with 
the LHV’s or LHW’s assessment of client eligibility. If the LHV’s or LHW’s assessment agrees with the gold 
standard nurse’s assessment, the screening is deemed appropriate.  


 
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Analytical model 
We will test the non-inferiority hypothesis that LHWs can screen potential DMPA clients for method 
initiation just as adequately as LHVs with a non-inferiority margin of 7.5%. Given the relationship 
between LHWs and LHVs within clinics, we will employ a generalized mixed model using a logit link to 
account for the correlations of participant outcomes within providers and providers within clinics. 
Random effects will be included for clinics and providers within clinic. The non-inferiority test will be 
conducted at a 5% significance level. A similar approach will be used to compare appropriate counseling. 
No covariate adjustments are planned for the primary analyses. However, exploratory analyses will 
include the following covariates: LHV/LHW age, marital status, education level, years of service, years of 
experience with DMPA, and average DMPA-IM injections given per month prior to the trial. Years of 
service, years of experience with DMPA, and average injections per month will be analyzed either as 
categorical or continuous variables based on exploratory analyses; either odds ratios or beta coefficients 
will be reported.  
As part of the blind analysis review, we will ascertain whether or not study outcomes differ for rural and 
urban sites. If they do not differ, as anticipated, we will combine the data from the five sites in Karachi 
with the five sites in Thatta. If differences are detected via descriptive analyses, we will present stratified 
results, but will be unable to test for significant differences as the trial was not powered for that 
purpose. In that event, the focus will be on the urban sites only, whose sample size (n=342) was 
powered to test the non-inferiority hypothesis. 
Other comparisons between groups will be primarily descriptive to explore the differences in the 
provision of DMPA services and client satisfaction measures by each cadre of provider, by DMPA type 
and urban/rural setting if those data are not pooled. Similarly, objective and provider-perceived 
comparisons between injection techniques and injection characteristics, respectively, will be primarily 
descriptive and exploratory.  
Analyses by Objective 
 
Objective 1: 
To assess whether LHWs can screen and initiate women on DMPA injections as safely 
and effectively as LHVs. 
To answer this objective, the analysis will report the odds ratio of appropriate screening and counseling 
by LHWs compared with LHVs using multi-level generalized mixed models as described above. The 
generalized linear mixed model accounts for the multilevel structure of the data (i.e., clinics and 
providers).  
Objective 2: 
Assess whether DMPA clients of Lady Health Workers and Lady Health Visitors are equally 
satisfied with their respective providers and the family planning services they provide. 
Descriptive analysis will be completed using indicators of client satisfaction and client-provider 
interactions for LHW and LHV clients. 
 


 
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Table 2: Summary of analysis approach and data sources for the primary and secondary outcomes 
Outcome 
Analysis 
Stratified by 
Source 
Objective 1 Outcomes 
Screening for DMPA use 
GLMM and 
descriptive 
Cadre, 
urban/rural 
Observation checklist of screening and 
gold-standard nurse’s assessment 
Counseling/Discussion of DMPA 
side effects, danger/warning 
signs, advantages and 
disadvantages 
GLMM and 
descriptive 
Cadre, 
urban/rural 
Observation checklist of screening 
Appropriate injection technique* 
Descriptive 
Cadre, 
urban/rural 
Observation checklist for DMPA-IM, q1-
q17; 
Observation checklist for DMPA-SP, q1-
q22 
Needle stick injuries* 
Descriptive 
Cadre, 
urban/rural 
LHW/LHV questionnaire 
Use of client (re)injection log* 
Descriptive 
urban/rural 
LHW/LHV questionnaire, qLHW6 
Objective 2 Outcomes 
Client satisfaction with DMPA* 
Descriptive 
Cadre, DMPA 
type 
Client exit interview, q313 
Client satisfaction with service 
delivery* 
Descriptive 
Cadre, DMPA 
type 
 
Client exit interview, q318 
Client comfort asking provider 
questions* 
Descriptive 
Cadre, DMPA 
type 
 
Client exit interview, q303 
Friendly and respectful behavior 
by provider* 
Descriptive 
Cadre, DMPA 
type 
 
Client exit interview, q301 
* If the data are pooled, there will be no urban/rural stratification 
Objective 1 Table Shells: Screening and counseling for DMPA  
Table 1: Odds of appropriate screening and counseling for DMPA initiation by Lady Health Workers 
compared with Lady Health Visitors in Pakistan 
 
OR 
90%CI 
p-value 
 
 
 
 
 
 
 
Appropriate screening 
 
 
 
 
 
 
Appropriate counseling 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appropriate screening defined as agreement between the provider and independent assessment by a gold standard nurse 
Appropriate counseling defined as having discussed side effects, warning/danger signs, advantages, and disadvantages of 
DMPA  
95% CI and p-value reported for test of non-inferiority  
 
 


 
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Table 2: Exploratory analysis of factors affecting appropriate screening for DMPA initiation by Lady 
Health Workers compared with Lady Health Visitors in Pakistan 
 
N (%) 
OR (or β)  
95%CI 
p-value 
Age  
 
 
 
 
 
 
 
Age cat 1 
 
 
 
 
 
 
 
Age cat 2 
 
 
 
 
 
 
 
Etc.  
 
 
 
 
 
 
 
Marital status 
 
 
 
 
 
 
 
Marital status 1 
 
 
 
 
 
 
 
Marital status 2  
 
 
 
 
 
 
 
Etc.  
 
 
 
 
 
 
 
Education level  
 
 
 
 
 
 
 
Education level 1 
 
 
 
 
 
 
 
Education level 2 
Etc. 
 
 
 
 
 
 
 
Years of service  
 
 
 
 
 
 
 
Categorical or 
continuous TBD  
 
 
 
 
 
 
 
Years of DMPA 
experience 
 
 
 
 
 
 
 
Categorical or 
continuous TBD 
 
 
 
 
 
 
 
Avg. DMPA 
injections/month  
 
 
 
 
 
 
 
Categorical or 
continuous TBD 
 
 
 
 
 
 
 
Appropriate screening defined as agreement between the provider and independent assessment by a gold standard nurse 
 
 


 
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Table 3: Exploratory analysis of factors affecting appropriate counseling for DMPA initiation by Lady 
Health Workers compared with Lady Health Visitors in Pakistan 
 
N (%) 
OR (or β)  
95%CI 
p-value 
Age  
 
 
 
 
 
 
 
Age cat 1 
 
 
 
 
 
 
 
Age cat 2 
 
 
 
 
 
 
 
Etc.  
 
 
 
 
 
 
 
Marital status 
 
 
 
 
 
 
 
Marital status 1 
 
 
 
 
 
 
 
Marital status 2  
 
 
 
 
 
 
 
Etc.  
 
 
 
 
 
 
 
Education level  
 
 
 
 
 
 
 
Education level 1 
 
 
 
 
 
 
 
Education level 2 
Etc. 
 
 
 
 
 
 
 
Years of service  
 
 
 
 
 
 
 
Categorical or 
continuous TBD  
 
 
 
 
 
 
 
Years of DMPA 
experience 
 
 
 
 
 
 
 
Categorical or 
continuous TBD 
 
 
 
 
 
 
 
Avg. DMPA 
injections/month  
 
 
 
 
 
 
 
Categorical or 
continuous TBD 
 
 
 
 
 
 
 
Appropriate counseling defined as having discussed side effects, warning/danger signs, advantages, and disadvantages of 
DMPA 
 
 
Table 4: Comparison of Lady Health Workers and Lady Health Visitors on DMPA service delivery 
indicators (n, %) 
  
Urban 
Rural 
 
LHW  
LHV 
LHW 
LHV 
Appropriate screening 
 
 
 
 
 
 
 
 
Appropriate counseling 
 
 
 
 
 
 
 
 
side effects 
 
 
 
 
 
 
 
 
danger signs 
 
 
 
 
 
 
 
 
advantages/disadvantages 
 
 
 
 
 
 
 
 
Appropriate injection technique 
 
 
 
 
 
 
 
 
Needle stick injuries 
 
 
 
 
 
 
 
 
Client log maintained 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
 
 


 
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Objective 2: Client Satisfaction and Client-Provider Interaction 
Table 5: Exemplar of Client Satisfaction and Client-Provider Interaction items (n, %)  
 
LHW 
LHV 
  
SP 
IM 
SP 
IM 
Satisfaction with method 
 
 
 
 
 
 
 
 
very satisfied 
 
 
 
 
 
 
 
somewhat satisfied 
 
 
 
 
 
 
 
not satisfied 
 
 
 
 
 
 
 
Satisfaction with services 
 
 
 
 
 
 
 
 
very satisfied 
 
 
 
 
 
 
 
somewhat satisfied 
 
 
 
 
 
 
 
not satisfied 
 
 
 
 
 
 
 
Satisfaction with provider  
 
 
 
 
 
 
 
very satisfied 
 
 
 
 
 
 
 
somewhat satisfied 
 
 
 
 
 
 
 
not satisfied 
 
 
 
 
 
 
 
Comfort asking questions 
     yes 
     no 
 
 
 
 
 
 
 
 
  
    
    
    
  
  
 
 
 


 
Statistical Analysis Plan, Study #1035709 
Version 1.0 Last updated: August 15, 2018  
 
 
 
 
 
Page 12 
 
Figure 1: Graphic presentation of observation checklist for screening