Hear us! Accounts of people treated with injectables for drug-resistant TB.

BACKGROUND: WHO drug-resistant TB (DR-TB) treatment recommendations now emphasize all-oral regimens, recommending against certain injectable agents and deprioritizing others due to inferior safety and efficacy. Despite increasing focus on patient-centered care, we are not aware of systematic attempts to qualitatively document patients' perspectives on injectable agents. This may inform implementation of WHO guidelines, emphasizing the importance of consultation with affected communities. METHODS: Testimonies were provided by TB survivors who experienced hearing loss from treatment with injectable agents. Testimonies were submitted in writing in response to minimal, standardized, open-ended prompts. Participants provided a signed consent form (with options to participate anonymously or as a named co-author), and later gave input into the overall shape and recommendations of the article. RESULTS: Fourteen TB survivors in 12 countries contributed testimonies. The following common themes emerged: lack of access to appropriate testing, information, treatment, or a collaborative treatment environment; the power of supportive care and social environments; stigma and isolation from TB treatment itself and resultant disability; and inaccessibility of cochlear implants. CONCLUSIONS: Survivor testimonies indicate strong preferences for avoidance of injectable agents, supporting rapid implementation of revised WHO guidelines, as well as for quality and supportive care for both TB and disabilities.

CONTEXTE: Les recommandations de l'OMS pour le traitement de la TB pharmacorésistante (DR-TB) mettent désormais l'accent sur les schémas thérapeutiques entièrement par voie orale, préconisant de ne pas utiliser certains agents injectables et de ne plus donner la priorité à d'autres en raison d'une innocuité et d'une efficacité inférieures. Malgré l'attention accrue portée aux soins centrés sur le patient, nous ne connaissons aucune étude systématique ayant cherché à documenter de manière qualitative le point de vue des patients sur les agents injectables. Ce travail pourrait guider la mise en place des directives de l'OMS, en mettant l'accent sur l'importance de consulter les communautés concernées. MÉTHODES: Des personnes ayant survécu à une TB et ayant connu une perte d'audition due à un traitement par agents injectables ont apporté leurs témoignages. Les témoignages ont été soumis par écrit en réponse à des questions courtes, ouvertes et standardisées. Les participants ont signé un formulaire de consentement (avec possibilité de participer de manière anonyme ou en tant que coauteur nommé) et ont ensuite contribué au format général et aux recommandations de l'article. RÉSULTATS: Quatorze personnes ayant survécu à une TB provenant de 12 pays ont apporté leur témoignage. Les thématiques suivantes ont été fréquemment mentionnées : manque d'accès aux tests, informations et traitements appropriés ou à un environnement thérapeutique collaboratif ; importance des soins de soutien et de l'environnement social ; stigmatisation et isolement dus au traitement antituberculeux et handicaps qui en résultent ; et inaccessibilité aux implants cochléaires. CONCLUSIONS: Le témoignage des personnes ayant survécu à une TB indique qu'elles préfèrent nettement éviter les agents injectables, allant ainsi dans le sens d'une mise en place rapide des directives révisées de l'OMS, et qu'elles préfèrent des soins de qualité et de soutien pour la TB mais aussi pour les handicaps qui en résultent.

Barriers and facilitators to early access of bedaquiline and delamanid for MDR-TB: a mixed-methods study.

SETTING: Phase II trials for bedaquiline (BDQ) and delamanid (DLM) were completed by 2011 and the drugs were approved by stringent regulatory authorities for the treatment of multidrug-resistant tuberculosis (MDR-TB) between 2012 and 2014. Manufacturers established 'early access' mechanisms to provide drugs before local registration. OBJECTIVE: To inform improvements in early access, we explored experiences of providers and advocates in accessing BDQ and DLM before the end of 2015 using a mixed-methods design. DESIGN: We examined barriers and facilitators to early access through an electronic survey. Barriers and facilitators were classified as occurring at the manufacturer- or country-level. We identified themes using inductive content analysis and illustrated themes through case studies. RESULTS: We analysed 41 survey responses from 36 respondents reporting on 22 countries; early access was attempted in 30 (73%) survey responses. Eligibility restrictions (11/30, 37%) and complicated and slow processes (8/30, 27%) were manufacturer-level barriers; access to companion drugs (10, 33%) and importation difficulties (4, 13%) were country-level barriers. Previous experience with manufacturer (3/30, 10%) and country processes (2/30, 7%) facilitated access. Eight case studies show the human impact of barriers and facilitators. CONCLUSION: Manufacturers and countries should develop transparent processes to permit early access, particularly for diseases that largely affect the poor, such as MDR-TB. Developers should plan for this need and rapidly register drugs with proven benefit, prioritizing high-burden settings.

Global programmatic use of bedaquiline and delamanid for the treatment of multidrug-resistant tuberculosis.

SETTING: The World Health Organization recommended two new drugs, bedaquiline (BDQ) and delamanid (DLM), for the treatment of multidrug-resistant tuberculosis (MDR-TB) in 2013 and 2014, respectively. An estimated one third of patients with MDR-TB would benefit from the inclusion of these drugs in their treatment regimens. DESIGN: A convenience sample of 36 countries voluntarily reported monthly data on cumulative programmatic use of new drugs to the Drug-Resistant TB Scale-Up Treatment Action Team between 1 July 2015 and 31 June 2017. Programmatic use was defined as treatment for MDR-TB with newer drugs outside of clinical trials or compassionate use. RESULTS: A total of 10 164 persons were started on BDQ and 688 started on DLM during the reporting period. Only 15.7% of the 69 213 persons estimated to need newer drugs over the study period were reported to have received them. CONCLUSION: While there has been significant progress in some countries, uptake of the newer drugs has not kept pace with a conservative estimate of need; fewer than 20% of persons likely to benefit from either BDQ or DLM have received them. Concerted efforts are needed to ensure that the newer drugs are made available more widely for persons with MDR-TB in need of these therapeutic options.

The devil we know: is the use of injectable agents for the treatment of MDR-TB justified?

For decades, second-line injectable agents (IAs) have been the cornerstone of treatment for multidrug-resistant tuberculosis (MDR-TB). Although evidence on the efficacy of IAs is limited, there is an expanding body of evidence on the serious adverse events caused by these drugs. Here, we present the results of a structured literature review of the safety and efficacy of IAs. We review the continued widespread use of these agents in the context of therapeutic alternatives-most notably the newer TB drugs, bedaquiline and delamanid-and from the context of human rights, ethics and patient-centered care. We conclude that there is limited evidence of the efficacy of IAs, clear evidence of the risks of these drugs, and that persons living with MDR-TB should be informed about these risks and provided with access to alternative therapeutic options.

Activism on rifapentine pricing: removing cost barriers to improve the uptake of tuberculosis research innovations.

As recent advances have been made in developing tools to fight tuberculosis (TB), there is also a trend towards increasing advocacy by the civil society for TB research and access. One recent successful effort to increase access to treatment options for TB involved a collaborative effort to identify the need for and barriers to the use of rifapentine (RPT) use in the United States. Survey responses confirmed the under-utilization of RPT: 82% of survey respondents selected cost as a significant or potential barrier to use. Survey results provided data to support a year-long advocacy campaign urging the drug company Sanofi to lower the price of RPT. This campaign was based on a common evidence base built in part by the stakeholders themselves. After multiple engagements with communities and providers, Sanofi US announced on 12 December 2013 that they would drop the price of RPT to US$32 per blister pack of 32 tablets for US public health programs. While further work remains to secure access to RPT in the United States and worldwide, the lowering of the price of RPT reflects the positive impact that collaborative advocacy can accomplish, and sets an example for other drug companies to follow.

Comme de récents progrès ont été réalisés dans l'élaboration d'outils de lutte contre la tuberculose (TB), on note également une tendance de la société civile à s'impliquer davantage dans la recherche et l'accès au traitement. Une activité récente couronnée de succès, visant à accroitre l'accès aux différentes options thérapeutiques de la TB, a impliqué un effort d'identification des besoins de rifapentine (RPT) aux Etats-Unis et des obstacles à son utilisation. Les réponses à l'enquête ont confirmé la sous-utilisation de la RPT : 82% des répondants ont estimé que son coût était un obstacle significatif ou potentiel à son utilisation. Ces résultats ont constitué des données permettant de soutenir une campagne de plaidoyer d'une année exhortant le fabricant, Sanofi, à réduire le prix de la RPT. Cette campagne a été basée sur un ensemble de preuves rassemblées en partie par les partenaires eux-mêmes. Après de multiples consultations avec les communautés et les fournisseurs, le 12 décembre 2013, Sanofi Etats-Unis a annoncé qu'ils allaient diminuer le prix de la RPT à US$32 par blister de 32 comprimés destinés aux programmes de santé publique américains. Même s'il reste du travail à faire pour sécuriser l'accès à la RPT aux Etats-Unis et dans le monde, la réduction du prix de la RPT témoigne de l'impact positif que le plaidoyer collaboratif peut avoir et constitue un exemple que les autres sociétés fabricant des médicaments devraient suivre.

Con el progreso reciente de los recursos destinados a combatir la tuberculosis (TB), se observa además una evolución en favor de la promoción de la causa de la investigación en TB y del acceso a sus resultados por parte de la sociedad civil. Una intervención reciente eficaz, encaminada a aumentar el acceso a las opciones de tratamiento antituberculoso, comportó un esfuerzo conjunto encaminado a reconocer la necesidad del uso de la rifapentina (RPT) en los Estados Unidos y los factores que obstaculizan su utilización. Las respuestas a una encuesta confirmaron la subutilización de la RPT; el 82% de quienes respondieron refirió el costo como un obstáculo importante o posible a su uso. Los datos de la encuesta respaldaron la utilidad de una campaña de promoción de la causa de un año de duración que instaba a la empresa Sanofi a disminuir el precio de la RPT. Esta campaña se basó en una serie de indicios aportados en parte por los mismos interesados directos. Después de celebrar múltiples compromisos con las comunidades y los profesionales de salud, Sanofi US anunció el 12 de diciembre del 2013 que disminuiría el precio de la RPT a US$32 por cada blíster de 32 comprimidos para los programas de salud pública en los Estados Unidos. Aunque todavía se precisan nuevas iniciativas que garanticen el acceso a la RPT en los Estados Unidos y en el mundo, la disminución del precio de este medicamento destaca el efecto positivo que puede lograr una promoción colectiva de la causa y constituye un ejemplo que deberían seguir otras empresas farmacéuticas.

Novel pediatric delivery systems for second-line anti-tuberculosis medications: a case study.

Tens of thousands of children are sick with multidrug-resistant forms of tuberculosis (MDR-TB), but there are limited child-friendly delivery systems for second-line medications. This case study presents the development of a granular dosing spoon pediatric delivery system for para-aminosalicylic acid. This product is the first of its kind for MDR-TB and could serve as a model for the development of other urgently needed pediatric delivery systems for second-line anti-tuberculosis drugs.