Economic evaluation of shortened, bedaquiline-containing treatment regimens for rifampicin-resistant tuberculosis (STREAM stage 2): a within-trial analysis of a randomised controlled trial

Background The STREAM stage 2 trial assessed two bedaquiline-containing regimens for rifampicin-resistant tuberculosis: a 9-month all-oral regimen and a 6-month regimen containing an injectable drug for the first 2 months. We did a within-trial economic evaluation of these regimens. Methods STREAM stage 2 was an international, phase 3, non-inferiority randomised trial in which participants with rifampicin-resistant tuberculosis were randomly assigned (1:2:2:2) to the 2011 WHO regimen (terminated early), a 9-month injectable-containing regimen (control regimen), a 9-month all-oral regimen with bedaquiline (oral regimen), or a 6-month regimen with bedaquiline and an injectable for the first 2 months (6-month regimen). We prospectively collected direct and indirect costs and health-related quality of life data from trial participants until week 76 of follow-up. Cost-effectiveness of the oral and 6-month regimens versus control was estimated in four countries (oral regimen) and two countries (6-month regimen), using health-related quality of life for cost-utility analysis and trial efficacy for cost-effectiveness analysis. This trial is registered with ISRCTN, ISRCTN18148631. Findings 300 participants were included in the economic analyses (Ethiopia, 61; India, 142; Moldova, 51; Uganda, 46). In the cost-utility analysis, the oral regimen was not cost-effective in Ethiopia, India, Moldova, and Uganda from either a provider or societal perspective. In Moldova, the oral regimen was dominant from a societal perspective. In the cost-effectiveness analysis, the oral regimen was likely to be cost-effective from a provider perspective at willingness-to-pay thresholds per additional favourable outcome of more than US$4500 in Ethiopia,$1900 in India, $3950 in Moldova, and$7900 in Uganda, and from a societal perspective at thresholds of more than $15 900 in Ethiopia,$3150 in India, and $4350 in Uganda, while in Moldova the oral regimen was dominant. In Ethiopia and India, the 6-month regimen would cost tuberculosis programmes and participants less than the control regimen and was highly likely to be cost-effective in both cost-utility analysis and cost-effectiveness analysis. Reducing the bedaquiline price from$1·81 to $1·00 per tablet made the oral regimen cost-effective in the provider-perspective cost-utility analysis in India and Moldova and dominate over the control regimen in the provider-perspective cost-effectiveness analysis in India. Interpretation At current costs, the oral bedaquiline-containing regimen for rifampicin-resistant tuberculosis is unlikely to be cost-effective in many low-income and middle-income countries. The 6-month regimen represents a cost-effective alternative if injectable use for 2 months is acceptable

Challenges in Tuberculosis Clinical Trials in the Face of the COVID-19 Pandemic: A Sponsor’s Perspective

The COVID-19 pandemic has caused unforeseen and extreme changes in societal and health system functioning not previously experienced in most countries in a lifetime. The impact of the pandemic on clinical trials can be especially profound given their complexities and operational requirements. The STREAM Clinical Trial is the largest trial for MDR-TB ever conducted. Currently operating in seven countries, the trial had 126 participants on treatment and 312 additional participants in active follow up as of March 31, 2020. Areas of particular concern during this global emergency include treatment continuity, supply chain management and participant safety monitoring. This commentary highlights some of the challenges faced due to the pandemic and the steps taken to protect the safety of trial participants and the integrity of the trial

Severe maternal morbidity in Canada, 1991–2001

BACKGROUND: Although death rates are often used to monitor the quality of health care, in industrialized countries maternal deaths have become rare. Severe maternal morbidity has therefore been proposed as a supplementary indicator for surveillance of the quality of maternity care. Our purpose in this study was to describe severe maternal morbidity in Canada over a 10-year period, among women with or without major pre-existing conditions. METHODS: We carried out a retrospective cohort study of severe maternal morbidity involving 2 548 824 women who gave birth in Canadian hospitals between 1991 and 2000. Thirteen conditions that may threaten the life of the mother (e.g., eclampsia) and 11 major pre-existing chronic conditions (e.g., diabetes) that could be identified from diagnostic codes were noted. RESULTS: The overall rate of severe maternal morbidity was 4.38 per 1000 deliveries. The fatality rate among these women was 158 times that of the entire sample. Rates of venous thromboembolism, uterine rupture, adult respiratory distress syndrome, pulmonary edema, myocardial infarction, severe postpartum hemorrhage requiring hysterectomy, and assisted ventilation increased substantially from 1991 to 2000. The presence of major pre-existing conditions increased the risk of severe maternal morbidity to 6-fold. INTERPRETATION: Severe maternal morbidity occurs in about 1 of 250 deliveries in Canada, with marked recent increases in certain morbid conditions such as pulmonary edema, myocardial infarction, hemorrhage requiring hysterectomy, and the use of assisted ventilation