[Show abstract][Hide abstract] ABSTRACT: Both product innovation (e.g., more sensitive tests) and process innovation (e.g., a point-of-care [POC] testing programme) could improve patient outcomes.
To study the respective contributions of product and process innovation in improving patient outcomes.
We implemented a POC programme using Xpert(®) MTB/RIF in an out-patient clinic of a tertiary care hospital in India. We measured the impact of process innovation by comparing time to diagnosis with routine testing vs. POC testing. We measured the impact of product innovation by comparing accuracy and time to diagnosis using smear microscopy vs. POC Xpert.
We enrolled 1012 patients over a 15-month period. Xpert had high accuracy, but the incremental value of one Xpert over two smears was only 6% (95%CI 3-12). Implementing Xpert as a routine laboratory test did not reduce the time to diagnosis compared to smear-based diagnosis. In contrast, the POC programme reduced the time to diagnosis by 5.5 days (95%CI 4.3-6.7), but required dedicated staff and substantial adaptation of clinic workflow.
Process innovation by way of a POC Xpert programme had a greater impact on time to diagnosis than the product per se, and can yield important improvements in patient care that are complementary to those achieved by introducing innovative technologies.
The International Journal of Tuberculosis and Lung Disease 09/2015; 19(9):1084-90. DOI:10.5588/ijtld.15.0120 · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Successful point-of-care testing, namely ensuring the completion of the test and treat cycle in the same encounter, has immense potential to reduce diagnostic and treatment delays, and impact patient outcomes. However, having rapid tests is not enough, as many barriers may prevent their successful implementation in point-of-care testing programs. Qualitative research on diagnostic practices may help identify such barriers across different points of care in health systems.
In this exploratory qualitative study, we conducted 78 semi-structured interviews and 13 focus group discussions in an urban and rural area of Karnataka, India, with healthcare providers (doctors, nurses, specialists, traditional healers, and informal providers), patients, community health workers, test manufacturers, laboratory technicians, program managers and policy-makers. Participants were purposively sampled to represent settings of hospitals, peripheral labs, clinics, communities and homes, in both the public and private sectors.
In the Indian context, the onus is on the patient to ensure successful point-of-care testing across homes, clinics, labs and hospitals, amidst uncoordinated providers with divergent and often competing practices, in settings lacking material, money and human resources. We identified three overarching themes affecting point-of-care testing: the main theme is 'relationships' among providers and between providers and patients, influenced by the cross-cutting theme of 'infrastructure'. Challenges with both result in 'modified practices' often favouring empirical (symptomatic) treatment over treatment guided by testing.
Even if tests can be conducted on the spot and infrastructure challenges have been resolved, relationships among providers and between patients and providers are crucial for successful point-of-care testing. Furthermore, these barriers do not act in isolation, but are interlinked and need to be examined as such. Also, a test alone has only limited power to overcome those difficulties. Test developers, policy-makers, healthcare providers and funders need to use these insights in overcoming barriers to point-of-care testing programs.
PLoS ONE 08/2015; 10(8):e0135112. DOI:10.1371/journal.pone.0135112 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The successful cure of tuberculosis (TB) is dependent on adherence to treatment. Various factors influence adherence, however, few are easily modifiable. There are limited data regarding correlates of psychological distress and their association with non-adherence to anti-TB treatment.
In a trial of a new TB test, we measured psychological distress (K-10 score), TB-related health literacy, and morbidity (TBscore), prior to diagnosis in 1502 patients with symptoms of pulmonary TB recruited from clinics in Cape Town (n = 419), Harare (n = 400), Lusaka (n = 400), Durban (n = 200), and Mbeya (n = 83). Socioeconomic, demographic, and alcohol usage-related data were captured. Patients initiated on treatment had their DOTS cards reviewed at two-and six-months.
22 %(95 % CI: 20 %, 25 %) of patients had severe psychological distress (K-10 ≥ 30). In a multivariable linear regression model, increased K-10 score was independently associated with previous TB [estimate (95 % CI) 0.98(0.09-1.87); p = 0.0304], increased TBscore [1(0.80, 1.20); p <0.0001], and heavy alcohol use [3.08(1.26, 4.91); p = 0.0010], whereas male gender was protective [-1.47(-2.28, -0.62); p = 0.0007]. 26 % (95 % CI: 21 %, 32 %) of 261 patients with culture-confirmed TB were non-adherent. In a multivariable logistic regression model for non-adherence, reduced TBscore [OR (95 % CI) 0.639 (0.497, 0.797); p = 0.0001], health literacy score [0.798(0.696, 0.906); p = 0.0008], and increased K-10 [1.082(1.033, 1.137); p = 0.0012], and heavy alcohol usage [14.83(2.083, 122.9); p = 0.0002], were independently associated. Culture-positive patients with a K-10 score ≥ 30 were more-likely to be non-adherent (OR = 2.290(1.033-5.126); p = 0.0416].
Severe psychological distress is frequent amongst TB patients in Southern Africa. Targeted interventions to alleviate psychological distress, alcohol use, and improve health literacy in newly-diagnosed TB patients could reduce non-adherence to treatment.
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) is a major public health threat. But worldwide, the majority of people with symptoms consistent with TB start their care seeking in the private or informal sector. These numbers are particularly high in Asia.
Public-private mix (PPM) efforts have been introduced to reach these individuals, as soon as possible, with quality-assured diagnosis and treatment. Systematic approaches have been designed to reach all provider types. However, PPM schemes struggle to manage the scale of a fragmented and under-regulated private sector.
Opportunities are arising to introduce more systemic, scalable, and innovative approaches, including social businesses, insurance-based initiatives, intermediary agencies, regulatory regimes, and provider consolidation, with a heavy emphasis on the use of new information technologies.
These approaches combine the previous work on TB private sector engagement with structural solutions that make health systems function for all patients, regardless of the disease or whether patients seek care in the public or the private sector.
PLoS Medicine 06/2015; 12(6):e1001842. DOI:10.1371/journal.pmed.1001842 · 14.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Accurate and timely diagnosis is the first step for initiating effective treatment for tuberculosis (TB) and interrupting transmission. Worldwide, nearly one third of all TB cases go undetected or unreported each year. The emergence of extensively drug-resistant TB, in addition to challenges in detecting TB among children and people living with HIV has created an urgent need for better technologies. In the past 5 years, Xpert MTB/RIF has proved to be pathfinder for improved diagnosis. However, gaps remain. Currently, there is no molecular replacement for sputum smear microscopy at the level of peripheral laboratories. There is no simple, non-sputum-based biomarker test that can detect all forms of TB at the primary care level. There is also a need to align emerging TB drug regimens with appropriate companion diagnostics. This review describes advances in non-molecular and molecular diagnostics and their potential to fill the gaps in TB case detection.
[Show abstract][Hide abstract] ABSTRACT: Background:
There is growing concern that interferon-γ release assays (IGRAs) are being used off-label for the diagnosis of active tuberculosis (TB) disease in many high-burden settings, including India, where the background prevalence of latent TB infection is high. We analyzed the costs and consequences of using IGRAs for the diagnosis of active TB in India from the perspective of the Indian TB control sector.
Methods and findings:
We constructed a decision analytic model to estimate the incremental cost and effectiveness of IGRAs for the diagnosis of active TB in India. We compared a reference scenario of clinical examination and non-microbiological tests against scenarios in which clinical diagnosis was augmented by the addition of either sputum smear microscopy, IGRA, or Xpert MTB/RIF. We examined costs (in 2013 US dollars) and consequences from the perspective of the Indian healthcare sector. Relative to sputum smear microscopy, use of IGRA for active TB resulted in 23,700 (95% uncertainty range, UR: 3,800 - 38,300) additional true-positive diagnoses, but at the expense of 315,700 (95% UR: 118,300 - 388,400) additional false-positive diagnoses and an incremental cost of US$49.3 million (95% UR: $34.9 - $58.0 million) (2.9 billion Indian Rupees). Relative to Xpert MTB/RIF (including the cost of treatment for drug resistant TB), use of IGRA led to 400 additional TB cases treated (95% UR: [-8,000] - 16,200), 370,600 (95% UR: 252,200 - 441,700) more false-positive diagnoses, 70,400 (95% UR: [-7,900] - 247,200) fewer disability-adjusted life years averted, and US$14.6 million (95%UR: [-$7.2] - $28.7 million) (854 million Indian Rupees) in additional costs.
Using IGRAs for diagnosis of active TB in a setting like India results in tremendous overtreatment of people without TB, and substantial incremental cost with little gain in health. These results support the policies by WHO and Standards for TB Care in India, which discourage the use of IGRAs for the diagnosis of active TB in India and similar settings.
PLoS ONE 04/2015; 10(4):e0124525. DOI:10.1371/journal.pone.0124525 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While Indian studies have assessed care providers' knowledge and practices, there is no systematic review on the quality of tuberculosis (TB) care.
We searched multiple sources to identify studies (2000-2014) on providers' knowledge and practices. We used the International Standards for TB Care to benchmark quality of care.
Of the 47 studies included, 35 were questionnaire surveys and 12 used chart abstraction. None assessed actual practice using standardised patients. Heterogeneity in the findings precluded meta-analysis. Of 22 studies evaluating provider knowledge about using sputum smears for diagnosis, 10 found that less than half of providers had correct knowledge; 3 of 4 studies assessing self-reported practices by providers found that less than a quarter reported ordering smears for patients with chest symptoms. In 11 of 14 studies that assessed treatment, less than one third of providers knew the standard regimen for drug-susceptible TB. Adherence to standards in practice was generally lower than correct knowledge of those standards. Eleven studies with both public and private providers found higher levels of appropriate knowledge/practice in the public sector.
Available evidence suggests suboptimal quality of TB care, particularly in the private sector. Improvement of quality of care should be a priority for India.
The International Journal of Tuberculosis and Lung Disease 04/2015; DOI:10.5588/ijtld.15.0186 · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Current phenotypic testing for drug resistance in patients with tuberculosis is inadequate primarily with respect to turnaround time. Molecular tests hold the promise of an improved time to diagnosis.
A target product profile for a molecular drug-susceptibility test (DST) was developed on the basis of a collaborative effort that included opinions gathered from researchers, clinicians, policy makers, and test developers on optimal clinical and operational characteristics in settings of intended use. In addition, the current diagnostic ecosystem and the diagnostic development landscape were mapped.
Molecular DSTs for detecting tuberculosis in microscopy centers should ideally evaluate for resistance to rifampin, fluoroquinolones, isoniazid, and pyrazinamide and enable the selection of the most appropriate treatment regimen. Performance characteristics of DSTs need to be optimized, but compromises can be made that depend on the trade-off between a false-positive result and a false-negative result. The operational requirements of a test will vary depending on the site of implementation. However, the most-important considerations pertain to quality control, maintenance and calibration, and the ability to export data.
This target product profile defines the needs as perceived by the tuberculosis stakeholder community and attempts to provide a means of communication with test developers to ensure that fit-for-purpose DSTs are being developed.
The Journal of Infectious Diseases 04/2015; 211(suppl 2):S39-S49. DOI:10.1093/infdis/jiu682 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The potential available market (PAM) for new diagnostics for tuberculosis that meet the specifications of the high-priority target product profiles (TPPs) is currently unknown.
We estimated the PAM in 2020 in 4 high-burden countries (South Africa, Brazil, China, and India) for tests that meet the specifications outlined in the TPPs. The yearly PAM was estimated for the most likely application of each TPP.
In 2020 the PAM for all 4 countries together was estimated to be (1) 12M tests/year with a value of 48M-71M USD for a sputum smear-replacement test; (2) 16M tests/year with a value of 65M-97M USD for a biomarker test; (3) 18M tests/year with a value of 18M-35M USD for a triage test; (4) 12M tests/year with a value of 59M-2238M USD for a tuberculosis detection plus drug susceptibility test (DST) all-in-one or 1.5M tests/year for a DST that follows a positive tuberculosis detection test with a corresponding value of 75M-121M for both tuberculosis detection and DST.
Although there is a considerable potential market for novel tuberculosis diagnostics that fit the specification of the TPPs in the 4 high-burden countries, the actual market for an individual product remains uncertain.
The Journal of Infectious Diseases 04/2015; 211(suppl 2):S58-S66. DOI:10.1093/infdis/jiu817 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Xpert MTB/RIF testing is being used extensively in countries with a high burden of TB. However recent evidence suggests that it may not have the same accuracy or impact in high-income, low-burden TB countries.
A prospective, pragmatic study was done between March 2012 and March 2014 to determine the feasibility, test accuracy, and impact on TB disease management provided by the Xpert test in a remote, medically underserved, predominantly Inuit population in Iqaluit, Nunavut, Canada.
A total of 453 Xpert tests were run on sputum samples from 344 patients with suspected TB. Twenty seven patients were identified as having active TB disease by culture. There were no cases of drug resistant TB. Using culture as the gold standard, one Xpert test compared to 1,2 or 3 sputum samples cultured per patient, had a sensitivity of 85% (66-95, CI 95%) and a specificity = 99% (97-100, CI 95%) for detection of MTB. The indeterminate rate was 4.4% of all samples run. Treatment initiation was significantly shortened using Xpert versus the national standard of three smears (1.8 vs 7.7 days, p <0.007), and particularly shorter in smear-negative, culture-positive cases (1.8 vs 37.1 days, p value< 0.008).
In a predominantly Inuit population in a remote region of Canada where the burden of TB is high and no TB testing facilities are available, on-site Xpert was feasible, accurate and shortened time to TB treatment initiation.
[Show abstract][Hide abstract] ABSTRACT: Interview with Professor Madhukar Pai, MD, PhD by Claire Raison (Commissioning Editor) Professor Madhukar Pai did his medical training and community medicine residency in Vellore, India. He completed his PhD in epidemiology at the University of California, Berkeley (CA, USA) and a postdoctoral fellowship at the University of California, San Francisco (CA, USA). He is currently an associate professor of epidemiology at McGill University in Montreal (Canada). He serves as the Director of Global Health Programs, and as an Associate Director of the McGill International Tuberculosis Centre. In addition, he serves as a Consultant for the Bill & Melinda Gates Foundation. He also serves on the Scientific Advisory Committee of the Foundation for Innovative New Diagnostics, Geneva, Switzerland. His research is focused on improving the diagnosis and treatment of tuberculosis, especially in high-burden countries such as India and South Africa. His research is supported by grant funding from the Gates Foundation, Grand Challenges Canada and Canadian Institutes of Health Research. He has more than 200 peer-reviewed publications. He is recipient of the Union Scientific Prize, Chanchlani Global Health Research Award and Stars in Global Health award from Grand Challenges Canada, and is a member of the Royal Society of Canada.