Incorporating User Needs into Product Development ...

Incorporating User Needs into Product Development for Improved Infection Detection for Malaria Elimination Programs K. B. Ebels, C. Clerk, C. H. Crudder, S. McGray, K. Magnuson, K. Tietje, P. LaBarre Technology Solutions PATH Seattle, USA

Abstract—In malaria-eliminating regions, a large proportion of ongoing transmission is attributed to low-density and subclinical infections that cannot be readily detected by currently available diagnostic tools. Accordingly, passive case detection strategies that dominate the focus of control programs need to be augmented by active infection detection (ID) tactics and more accurate diagnostic tools in an elimination context. To address this need, we are developing a target product profile (TPP) for a diagnostic test intended for use in active ID settings. To ensure the TPP incorporates the needs of users and the contexts in which active ID is implemented, we conducted field research in five representative countries across the spectrum of regional programs ranging from control to elimination. Using ethnographic interviewing, we gained an understanding of the contexts in which the test will be used and the constraints users encounter in successfully conducting active ID efforts. These findings inform the TPP and provide insight into operational conditions that must be addressed in parallel to product development. The results provide clear guidance for programmatic and technical initiatives, ensuring development and validation of innovative tools and tactics aimed at supporting successful elimination campaigns are well grounded in the needs identified by users. Keywords—malaria elimination, product development, user needs

I. INTRODUCTION Malaria is a blood-borne infection caused by the genus Plasmodium, a protozoan parasite that is transmitted to humans by infectious female Anopheles mosquitoes. There are four species of Plasmodium that are known to infect humans: P. falciparum, P. vivax, P. malariae, and P. ovale, while a fifth species, P. knowlesi, has been implicated in zoonotic transmission in Southeast (SE) Asia [1]. Malaria has been the most important parasitic disease afflicting Homo sapiens throughout human history [2] and remains to this day a devastating disease despite being a preventable and treatable infection. In 2012, there were estimated to be 207 million cases of malaria worldwide, with 80% of those cases occurring in sub-Saharan Africa (SSA), and resulting in 627,000 deaths [3]. Despite the continued transmission and disease associated with malaria, there has been remarkable

progress in controlling malaria [4-7]. Between 2000 and 2012, the mortality rates declined 42% globally, and the incidence rate dropped by 25% [3]. As a result of declining transmission, some countries are actively pursuing elimination of malaria where feasible. As countries move from control of malaria toward elimination, strategies need to change. A cornerstone in malaria control strategy is to identify malaria cases through parasite-confirmed diagnosis and prompt treatment. This is accomplished by identifying febrile cases that present within the health system and have malaria-like signs and symptoms. This process, where sick individuals present to the health system (either in the community or in a health facility with a microscope), is termed passive case detection (PCD). However, malaria is a chronic disease, where parasites can also be found in the general population within individuals who do not show any clinical signs or symptoms of malaria infection [8]. These asymptomatic infected individuals, who can be found in both high- and low-transmission settings [7,9], can act as reservoirs that can sustain transmission in an area [5]. Because PCD does not capture these individuals, they go unnoticed in the community; thus, efforts to disrupt transmission and eliminate the parasite from that region will not be successful unless these asymptomatic infections are actively sought out [8]. To disrupt transmission with elimination as the end goal, new strategies are required that consist of proactive tactics to identify reservoirs in the community and treat them [10]. These new tactics are generally described as active infection detection (ID) because the goal is to actively seek out all infections in a community, regardless of the presence of symptoms. The fundamental principle behind active ID is to identify and treat parasite reservoirs in the community, namely asymptomatic hosts [7]. However, one difficulty in detecting these groups is that they often harbor low-density infections [11], where the levels of parasites circulating within these hosts are lower than the detection limits of existing diagnostic

This work was funded by a grant from the Bill & Melinda Gates Foundation.

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tests [8]. In an elimination setting, where transmission levels are very low, there is a corresponding rise in asymptomatic infections [12]. Furthermore, sub-patent carriers have been estimated to be responsible for 20% to 50% of human-tomosquito transmission [13]. Failure to detect and treat these reservoirs will hinder elimination efforts. The use of lowsensitivity rapid diagnostic tests (RDTs) has been implicated in the failure to reduce morbidity in a recent trial utilizing testand-treat strategies in Kenya and Burkina Faso [14]. Despite the test-and-treat intervention, low-density infections were missed by RDTs and, therefore, reservoirs continued to persist in the community and contributed to ongoing transmission. Existing diagnostic technologies used in the field are not sufficient to meet the needs of elimination programs.

The bulk of morbidity and mortality due to malaria resides in SSA and SE Asia [3]; therefore, we selected countries from these regions. We conducted interviews in China, Ethiopia, Tanzania (Zanzibar), Thailand, and Zambia. We tried to span, within time and resource constraints, a broad spectrum of elimination programs including strategy, planning, and implementation. We also selected countries with representative and unique attributes relevant to elimination. See Table I for comparison of these criteria in the countries we visited. TABLE I.

China

To ensure these low-density infections are identified, new diagnostic technologies are urgently needed that are more sensitive than microscopy and RDTs, but also amenable to active ID use case scenarios [5,7]. Any novel ultra-sensitive platform will have to conform to the context where it will be used. Developers must design a new technology to fit the technical needs of end-users but must also be aware of the constraints facing elimination program staff during their active ID activities. At this early stage of the target product profile (TPP) development process, we have an opportunity to ensure that an appropriate diagnostic tool is developed, applying lessons learned from the initial development and introduction of RDTs [15]. This means engaging all levels of stakeholders at an early stage, analyzing feedback, and ensuring that it informs the TPP of an improved diagnostic technology [16]. The aim of this exercise was to make informed and validated decisions in drafting a TPP for a novel diagnostic technology specifically designed for active ID activities and to ensure that the needs across a range of relevant stakeholders are represented in the TPP.

Representative situations High importation risk; returning infected laborers from subSaharan Africa (SSA) [20] and remote hotpopsa in Yunnan Province [21]. Planning for demonstration study in Amhara Region, not actively engaged in active infection detection (ID) interventions yet.

Achieve elimination in areas with historically low transmission by 2015 [22].

Tanzania (Zanzibar)

Zero locally acquired malaria cases by 2017 [23]. Eliminate malaria in 80% of the country by 2020 [25].

Island with high importation risk; two previous attempts at elimination. Elimination efforts ongoing with Mobile Malaria Units using active ID tactics.

Establish and maintain five malaria-free areas by 2015; 16% prevalence in 2010 [28].

Elimination efforts ongoing; select districts implementing active ID interventions in rural and urban settings.

Thailand

Zambia

a.

Elimination goals Elimination should be achieved nationally by 2020 [19].

Ethiopia

II. METHODOLOGY We conducted field research between April and November 2013 to gain an in-depth understanding of user needs for an improved diagnostic test to successfully carry out elimination activities. In order to understand what conditions are most critical to the success or failure of a technology, differences in environments of use need to be explored firsthand [17]. We conducted ethnographic interviews focusing on what users do and how they do it, interacting with users in their environments, and observing their behaviors and current practices [18]. As a result, we gained an understanding of the context in which a new technology would be used and identified constraints users currently face in carrying out tasks according to malaria control and elimination policies. A research determination committee determined that this work did not require institutional board approval. We gained permission from the ministry of health (MOH) in each country prior to conducting interviews.

COUNTRIES SELECTED FOR INTERVIEWS Additional attributes Dried blood spots (DBS) sent to central lab for confirmation with polymerase chain reaction (PCR).

Migrant population working in remote endemic areas reseeding transmission in malaria-free areas. Ethiopia is a country with significant Plasmodium vivax co-endemicity with Plasmodium falciparum. Intensified malaria control has resulted in very low levels of malaria incidence [24]. Emergence of artemisinin resistance requires urgent need for elimination [26]; drug efficacy monitoring [27]. Planned monitoring and evaluation of active ID interventions with PCR from DBS collected during malaria indicator surveys

Hotpops are demographically clustered populations of malaria incidence. In an elimination context, hotpops are often associated with travel history and occupation. This term was adapted from the Malaria Elimination Group at the University of California San Francisco.

We interviewed thought leaders (persons addressing the problem of malaria at the strategic level such as researchers, policymakers, manufacturers, and strategists) and program personnel (persons who are working in or with the public health system to implement malaria strategies but who do not directly see patients or handle diagnostic tests). These

interviews included people from academic and research institutions, international nongovernmental organizations, donors, industry, MOH, and malaria programs from the national levels down to district levels, military, pharmacy, procurement, and refugee and migrant labor agencies. Our intent was to cover the range of participants addressing malaria. Additionally, we interviewed end-users, defined as those who see patients and/or handle malaria diagnostic tests. These interviews spanned a wide range of users and settings in order to ensure we encompassed all levels of the health care system (see Fig. 1). The range of participants interviewed across countries is outlined in Table II. In each interview, we gathered information and observations related to the health system, the context, and the constraints. This includes specific elements such as policies, priorities, current practices, human resources, settings, workload, infrastructure, diagnostic tools used, supplies, and desired product attributes. Following the completion of all interviews, we classified information across countries and interviewees by use-scenario. Our consolidated findings illustrated the contexts of these usescenarios. In addition to representing the context, we performed analysis of the findings to identify constraints. Multiple team members reviewed interview notes, identifying and cross-checking constraints to ensure robustness of output before translating them into user needs. These needs were then correlated to TPP attributes. As we drafted the TPP, the needs represented by a range of relevant stakeholders were incorporated into the requirements. Since our TPP focus is improved diagnostic tools to more effectively support active ID tactics, we mainly targeted our analysis on active ID use scenarios.. Because the duties of many of the end-users we interviewed encompass both PCD and active ID activities, and because workers performing PCD at very low levels of the health care system face many similar constraints, some of the information gathered from PCD use scenarios is also useful to inform user needs for performing diagnosis in active ID settings. Fig. 1. End-users interviewed encompassed a wide range of users across all levels of the health system in a variety of settings.

TABLE II.

China Ethiopia Tanzania (Zanzibar) Thailand Zambia

INTERVIEW PARTICIPANTS BY COUNTRY AND TYPE Thought leaders 3 18

Program staff 12 11

End users 5 7

3

9

3

7 2

10 6

10 11

III. RESULTS A. Context of Active Infection Detection Protocols for various active ID tactics depend on strategies as determined by national malaria control and elimination programs. Specific processes vary by country and region. However, by compiling observations across all interviews, we were able to sketch a typical environment in which active ID activities occur and how those activities are carried out. This information in itself informs many important parameters of product design such as the level of infrastructure available, the skill of the end-user, and the use of test results. The following descriptions characterize the typical contexts and activities of an active ID environment. Active ID activities may be completed in urban or rural settings with testing typically occurring in households, community centers, schools, workplaces, or within certain traveling groups such as migrant workers or people returning from malaria-endemic areas/countries. As such, there is often minimal infrastructure available to health workers conducting active ID activities. Health workers may need to travel beyond roads by motorbike, boat, or foot to reach the site. Once there, they may not have access to electricity, a clean water supply, or mobile phone service. Given the minimal amenities available at the site, health workers may need to conduct their activities on the floor in the absence of an elevated work surface. Furthermore, the amount of supplies a health worker can bring to the field is often limited by what he/she can carry in a backpack. Persons who carry out active ID activities display a wide range of skill levels. Some active ID activities may be conducted by a single community health worker (CHW) while other active ID activities may have robust teams that include program managers, malaria officers, doctors, and laboratory technicians. Additionally, assistance may be provided by local community health facilities or employers. Active ID may be initiated in response to a spike in positive malaria cases and/or an abnormal increase in prevalence as detected by surveillance systems through PCD. Alternatively, campaigns may be scheduled routinely for known hotspots (also referred to as foci, hotspots are large or small geographically clustered populations identified as having comparatively higher levels of transmission [29]), with two to three visits per year based on existing data. Target testing time frames may be communicated to communities in advance to maximize participation. Teams may make house-

to-house visits, reaching between 9 and 20 households per team per day and screening everyone in the household. Alternatively, a community may be notified of a central testing location(s) to which they can be mobilized for testing. Currently, RDTs or microscopy may be used for testing. In some cases, RDTs are used and blood slides are taken for problematic cases and for patients who have taken antimalarial treatment within the past two weeks. Occasionally, teams may take a dried blood spot on filter paper to send to a higher level health facility for polymerase chain reaction analysis. Workers detect and treat all persons testing positive within the bounds of their campaign, though a positive case may trigger an expanded range of screening. Teams collect, record, and submit data such as test results, questionnaire responses, demographic information, travel history, axillary temperature, and global positioning system coordinates. An environmental health technician or other team member may provide health education to the community and coordinate local vector control activities. Toward the end of regularly scheduled campaigns, revisits may be carried out. Understanding the active ID environment provides insights into product design requirements through direct observations TABLE III. TPP attributes Lowest infrastructure level

of the contexts of these use scenarios and processes that occur within them. We obtained further insight by probing into the constraints faced by users working in active ID use scenarios. B. Constraints and User Needs Identifying the constraints that hinder the success of active ID activities leads us to an understanding of what users need to counter these constraints; we can then incorporate these needs into the TPP attributes of an improved diagnostic test. For example, users identified that microscopes are heavy and difficult to carry into the field to do active ID. In addition to identifying specific microscopy-related constraints, we also observed that users may need to walk significant distances to reach communities and that transportation may be difficult during rainy seasons. In this example, the constraints related to microscopy, transportation, and weather indicate that users need an improved technology to be light and easy to transport. Therefore, the TPP attribute addressing “portability” is informed by these constraints and user needs. Table III below outlines additional attributes of the TPP that are informed by user needs derived from constraints that were documented during the interviews.

USER NEED INPUTS TO TARGET PRODUCT PROFILE ATTRIBUTES

User need input informed by constraints Tests are administered in settings where there may be no access to electricity, water, or communications; that may require transport by foot; and that may be far from proper hazardous waste disposal.

Lowest level user

Tests are administered and interpreted by a minimally trained volunteer health worker.

Sample type/collection

Users desire less-invasive sample types; preferred types are saliva or urine, finger sticks are acceptable, venous blood draws are not acceptable.

Sample volume

Users desire a sample volume that can be easily collected with a finger stick, assuming sample type is whole blood.

Detection

Users expressed a need for test results to be clearly readable in poor lighting conditions. Many tests are performed in households with no light source.

Quality control

An indicator of damage to test or reagents due to heat exposure or expired reagents.

Supplies needed

Users prefer that all supplies needed for testing be included in a kit for ease of transport and to ensure all supplies are available.

Lancet

An auto-retracting lancet is preferred to minimize fear of community members during pricking. Users also need a lancet that can be safely stored until it can be properly disposed of.

Blood collection and transfer device

User preferences vary. Whereas highly trained lab staff found pipette models optimal, the community health workers (CHWs) tended to favor inverted cup and loop models. Each model had its own drawbacks. Novel designs are warranted to improve collection and transfer of sample to the device

Portability

Users must be able to carry all supplies needed for testing, treating, reporting, and storing waste in a backpack. Desired maximum weight varied but cannot exceed 10 kg for all materials in backpack. Users also need tools that are durable and can withstand transport over difficult terrain and potential exposure to heat and precipitation.

Safety

Users need a test that limits the risk of exposure to blood-borne pathogens. CHWs often temporarily store used RDTs and lancets in their homes until proper disposal can be made, therefore, secure containers for waste must be provided to protect family members from exposure to biohazardous waste until it can be properly disposed of.

Species differentiation

Users need to be able to differentiate species in order to ensure appropriate patient management and for reporting to the epidemiological surveillance system.

Diagnostic/Clinical sensitivity

A test that is better than current rapid diagnostic tests at detecting low-density infections is preferred by users. A one log increase in sensitivity is acceptable.

Diagnostic/Clinical specificity

A test with a false positive rate that is comparable to existing methods is acceptable by users.

TPP attributes Time to results

User need input informed by constraints A test with rapid results is preferred as health care workers have high workloads and are often traveling house to house. Often there are as many as ten household members that need to be tested within a one hour period. Therefore, a new diagnostic must be able to accommodate this number of tests.

Throughput

Users need to be able to run multiple tests in parallel in order to complete testing of a household in a timely manner. Stand-alone platforms that can test one sample per device is acceptable only if user can run up to five tests in parallel without compromising integrity of results. A platform able to run multiple samples on one device is acceptable if loading samples can be streamlined and samples can be easily tied to specific individuals to avoid patient mix-up.

Target shelf life/ stability

Users work under high temperatures (up to 42°C) as well as extreme fluctuations in temperature. A test should be stable under these conditions. A shelf life that extends well beyond the long time-frames of procurement and distribution would be ideal.

Ease of use

Many users cannot read English; instructions should be pictorial and in local language. The test should not require many timed steps.

Ease of results interpretation

Users prefer a test that provides a clear positive/negative result that is readable in poor lighting conditions. Indeterminate results must be easily identified.

Training requirements

Users should be able to easily administer the test with minimal training, such as one- or two-day workshop.

Calibration

Users need a test that requires minimal to no calibration.

Service and support

Users need a test that requires minimal to no maintenance.

Waste disposal

Users prefer a test with minimal waste and they need to be able to safely store the waste until it can be properly disposed of.

Power requirements

Users need a test that does not require power or that uses a solar rechargeable battery.

Water requirements

Users need a test that does not depend on a water supply.

Labeling

Users prefer test labels that clearly depict the test is for detection of malaria and include space on device for specimen labeling.

IV. DISCUSSION It is important to note that this activity has limitations and thus is not the defining aspect of confirming TPP domains. The countries we selected are not perfectly representative of all malaria-endemic areas around the globe, although we did cover as many endemic areas with varying epidemiological profiles as possible with the resources available. Our sampling of sites is not necessarily representative of the entire country; within national boundaries there are variations in constraints and enduser opinions. Finally, we did not visit any post-elimination states due to the observational nature of the data collection. This exercise is a starting point from which to continue vetting user requirements as product development continues. Despite these shortcomings, specific themes surfaced within each country as well as internationally. Unique constraints per country or use case scenario were generally operational or ecological in nature. A new technology is only able to alleviate certain constraints, and there are major external factors limiting success of elimination programs that must also be addressed. Stockouts of RDTs were a major limitation identified in almost every country we visited, and this issue is an inherent flaw within the system that cannot be alleviated by technology improvements. National Malaria Control Programs, and their donors, should pay heed to those constraints that technologies cannot address and strengthen those specific aspects within the health system. The donor community should also increase the funds to assist them in these efforts. This task is even more difficult to achieve than the development of novel technologies, especially as enthusiasm for funding malaria programs may wane with decreasing incidence.

TPPs are used to guide developers in designing prototypes that conform to the needs of the end-user and to ensure successful uptake into the market [30]. Traditionally, developers have over-emphasized the technical requirements of in vitro diagnostics without adequate focus on the needs of the end-user or other relevant stakeholders. For example, there is often a gap between analytical sensitivity found in validation settings and clinical sensitivity once devices have been released into the market. The analytical sensitivity is measured under well-controlled laboratory settings, thus the performance of the device is inherently a result of the test function. Once in the field, test performance is affected by user compliance to assay protocol and contextual aspects such as storage conditions or sample quality, among others, which can decrease performance and thus have a negative impact on product uptake or reduced utility for malaria programs. To inform and validate a TPP, it is imperative to conduct field work at an early stage, engaging all relevant stakeholders regarding technology needs and constraints. This will ensure that the design of the final product may alleviate, if possible, some of these restrictions to ensure the product will obtain the impact desired by malaria programs. For malaria elimination to be successful, new strategies aim to actively seek out reservoirs in the community, specifically chronically infected asymptomatic individuals that harbor lowdensity infections. Current in vitro diagnostics are unable to reliably detect these sub-patent infections. Tools with improved accuracy are required before elimination can be feasible. User experience is integral to ensuring that test development is guided by the reality on the ground. This exercise is an important step in initiating the development of such tests; engaging end users will also be essential as new tools proceed through the development pathway to ensure

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