In recent times, an extensive array of diagnostic examinations has become accessible for utilization in settings with limited resources. Consequently, a plethora of guidelines, assessments of performance, and reports on implementation have been generated. Nevertheless, this abundance of information lacks structure and exhibits inconsistent quality, posing challenges for end-users like clinics, laboratories, and health ministries to discern the most suitable test for enhancing clinical care and patient outcomes in a specific context. This article presents a stepwise guide, based on the practical experience of Médecins Sans Frontières, encompassing six stages for the selection and integration of in vitro diagnostic tests:
(i) delineate the test’s purpose;
(ii) scrutinize the market;
iii) confirm regulatory approval;
(iv) assess the test’s diagnostic precision under ideal conditions;
(v) appraise the test’s diagnostic precision in clinical practice; and
(vi) supervise the test’s performance in routine use.
Shortcomings in the information required to execute these six stages and deficiencies in regulatory frameworks are underscored. Finally, recommendations for enhancing the quality of diagnostic tests are proposed, including the establishment of a model catalog of essential diagnostics, creation of a repository containing information on diagnostic study design, and enhancement of quality control and postmarketing surveillance.
The utilization of diagnostic tests has become essential for the identification and surveillance of illnesses, delivering prognostic insights, and anticipating responses to treatment. Currently, there are over 40,000 products accessible globally for conducting in vitro diagnostic tests across a diverse range of conditions. These encompass conventional laboratory-based examinations, involving the dispatch of samples to a central laboratory for examination, and point-of-care tests, which can be executed in proximity to, or at, the location of patient care. Point-of-care testing contributes to enhancing the decision-making process for treatment, avoiding unnecessary referrals, streamlining care efficiency, and reducing expenses, particularly in settings with limited resources where laboratory infrastructure is deficient.
In this piece, we present a six-stage methodology to surmount the challenges faced by Médecins Sans Frontières when choosing and executing in vitro diagnostic tests. This strategy was deduced from an analysis of the diagnostic literature and our involvement in the implementation of diagnostic programs. We address the complexities associated with each of the six stages and delineate existing issues with the quality control of tests. We anticipate that this straightforward, step-by-step guide will aid clinics, organizations, and health ministries in making informed decisions regarding the selection of in vitro diagnostic tests and, in the more extended period, will contribute to crafting a pragmatic manual for choosing diagnostics.
Step 1: Test Definition
It is crucial to precisely articulate the purpose of the test, as this will impact many subsequent stages in the selection procedure. Factors to ponder include:
(i) the specific disease or condition targeted for diagnosis;
(ii) whether a single test or a diagnostic algorithm is needed; and
(iii) whether the test is intended or capable of delivering a qualitative or quantitative outcome.
Furthermore, for optimal clinical efficacy, one should contemplate:
(i) the testing location (e.g., a large laboratory or a small healthcare center); and
(ii) the end-user (e.g., a well-trained laboratory technician or a primary healthcare worker, such as a nursing assistant).
Other vital considerations encompass the clinical purpose of the test (e.g., whether a screening or confirmatory test is necessary) and the additional value brought by the test or a combination of tests.
Step 2: Examination of the Market
A thorough market review is essential to identify available tests for the targeted condition, involving consultation of guidance from international bodies like WHO and manufacturers’ product details. Product specifications encompass information on required sample types, test operating conditions, additional equipment needs, and shelf life. To assess the accuracy of manufacturers’ claims, scrutiny of peer-reviewed medical literature is crucial, as brochures or instructions may exaggerate a test’s diagnostic precision. Unfortunately, limited prosecutions address inappropriate claims, and local market challenges like counterfeit tests and regulatory gaps can impede the selection process.
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Step 3: Regulatory Validation
Numerous countries lack regulatory processes for evaluating the safety, quality, or efficacy of in vitro diagnostic tests, leading to the circulation and use of subpar tests. Consulting recommendations from global regulatory bodies aids test selection, especially for major conditions. For instance, WHO has instituted a prequalification process for tests related to diseases with significant health risks. This process evaluates product applications, conducts laboratory assessments, and inspects manufacturing sites, ensuring both performance and quality. However, the prequalification process doesn’t cover all conditions, leaving gaps in regulatory oversight.
Step 4: Attaining Optimal Diagnostic Precision
Evaluating a test under ideal conditions, such as phase-II studies, reveals its peak performance. This data is crucial for users to preselect a test suitable for real-world trials. These assessments not only focus on diagnostic accuracy but also on repeatability, reproducibility, and ease of use, along with batch variations. Regular evaluations for infectious diseases, like malaria tests by WHO and FIND, provide public results. However, many other conditions lack similar evaluations due to the need for high-quality infrastructure and skilled staff, often limited to reference laboratories.
Step 5: Practical Diagnostic Accuracy
Considerations for in vitro diagnostic tests should extend to their real-world performance and user-friendliness. End-user level evaluations (phase-III studies) offer insights into a test’s real-world performance and may reveal aspects not evident in phase-II studies. Environmental factors, user training levels, and conditions at the point of use can influence the test’s practical performance. Real-world evaluations should align with the intended population, providing context-specific accuracy data. If phase-III evaluations are absent, end-users might need to conduct their own assessments. National regulatory authorities often mandate phase-III studies before approving a test, and guidelines exist for specific diseases.
Step 6: Continuous Performance Monitoring
Monitoring a test’s routine performance is vital, involving regular quality control, proficiency testing, and end-user supervision. Long-term quality assurance includes postmarketing surveillance, typically handled by national authorities and incorporated into WHO’s prequalification process. Both reactive (response to complaints) and proactive (verifying production lot quality before and after distribution) surveillance are essential. Reports from end-users contribute to WHO’s prequalification process. Unfortunately, public access to end-users’ complaints and analyses is limited, with WHO only publishing field safety notices if complaints are validated.
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