Standards for clinical trials for treating TB.

BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.

Overcoming barriers to the access and uptake of newer drugs for multidrug-resistant TB.

To improve the unsatisfactory treatment outcomes of multidrug-resistant TB (MDR-TB), it is essential we use new regimens based on newer drugs. To address challenges in the introduction of BDQ and the shorter treatment regimen (STR), the USAID has committed to support countries receiving BDQ (through the USAID/Janssen Bedaquiline Donation Program), with targeted short-term technical assistance (TA). Six MDR-TB clinical consultants were recruited and provided TA to 17 countries between 2017 and 2019. Building on other in-country support, this short-term TA proved instrumental in overcoming barriers, such as misconceptions about BDQ safety, inadequate clinical skills to manage patients and limited expansion plans to increase access to BDQ and the STR.

Beyond 'cure' and 'treatment success': quality of life of patients with multidrug-resistant tuberculosis.

SETTING: Two drug-resistant tuberculosis (DR-TB) sites (MSF Clinic, Jupiter Hospital) in Mumbai, India. OBJECTIVE: To assess health-related quality of life (HRQoL) and associated factors among DR-TB patients and explore their perspectives about HRQoL. DESIGN: We used a mixed-methods design: a quantitative cross-sectional questionnaire (the World Health Organization's Quality of Life Brief Questionnaire [WHOQoL-BREF]); and qualitative in-depth interviews for purposively selected patients. Assessments were conducted between April and November 2016. RESULTS: Ninety-five patients completed WHOQoL-BREF; 12 were interviewed. The psychological and physical health domains were the most affected (mean scores 56.2 ± standard deviation [SD] 18.3, and 56.5 ± SD 15.1, respectively; maximum 100). The social relations and environmental domains mean scores were respectively 68.6 (SD ±21.1) and 60.3 (SD ±15.9). Loss of jobs due to TB adversely affected the social relations and environmental domains. Qualitative analysis showed that support was the most important theme affecting quality of life. Other themes were physical factors (e.g., treatment adverse events), psychological factors (e.g., depression), social functioning (e.g., fear of stigmatisation) and environmental factors (e.g., health systems). CONCLUSION: HRQoL was lower among study participants, but not as low as previously reported among TB patients. Support was the main factor that positively affected HRQoL, although both disease and treatment were physically and socially challenging.

Migration histories of multidrug-resistant tuberculosis patients from the Thailand-Myanmar border, 2012-2014.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a growing public health threat in South-East Asia. TB is typically a disease of poverty and can be spread by infectious humans who migrate from one region to another. DESIGN: We interviewed 20 MDR-TB patients on the Thailand-Myanmar border with regard to their migration histories. Migration origins and destinations were mapped. RESULTS: All but one participant had a history of migration, and maps of migration ranges revealed wide geographic dispersal. Most described living and work conditions that could contribute to the spread of drug-resistant TB, including numerous contacts and crowded living quarters. CONCLUSION: Our results show that at least some migrant workers in the region carry MDR-TB, and indicate that this subgroup of the population is important with regard to the transmission of MDR-TB throughout the region. Migrants in this region come into contact with high numbers of people and may be able to spread the disease across wide geographic ranges. Access to diagnosis and treatment and socio-economic development are at least as important as any TB control measures, meaning that innovative and bold approaches that extend across international borders are needed to address these problems.

Treatment of multidrug-resistant tuberculosis in a remote, conflict-affected area of the Democratic Republic of Congo.

The Democratic Republic of Congo is a high-burden country for multidrug-resistant tuberculosis. Médecins Sans Frontières has supported the Ministry of Health in the conflict-affected region of Shabunda since 1997. In 2006, three patients were diagnosed with drug-resistant TB (DR-TB) and had no options for further treatment. An innovative model was developed to treat these patients despite the remote setting. Key innovations were the devolving of responsibility for treatment to non-TB clinicians remotely supported by a TB specialist, use of simplified monitoring protocols, and a strong focus on addressing stigma to support adherence. Treatment was successfully completed after a median of 24 months. This pilot programme demonstrates that successful treatment for DR-TB is possible on a small scale in remote settings.