Maximizing TB clinical trial results to influence policy

Originally posted here on the Vital Strategies site.

Roughly 600,000 people contract multidrug-resistant tuberculosis (MDR-TB) each year, of whom approximately 40% die. As such MDR-TB remains a significant global health threat, especially for people living in low and middle-income countries. Until recently, the WHO-recommended treatment for MDR-TB lasted 20-24 months, resulting in significant burden and cost to both patients and health systems. MDR-TB treatments are expensive and can have serious side effects, including permanent hearing loss. As a result, only about half of all people who start treatment for MDR-TB successfully complete it.

In response to the difficult and limited treatment options available for treating MDR-TB, The Union, Vital Strategies and their partners are undertaking the STREAM clinical trial to evaluate shorter, more tolerable regimens for MDR-TB. STREAM is the first large-scale, multi-country clinical trial to examine shortened regimens for MDR-TB and is the first phase III trial to test the effectiveness and safety of bedaquiline within a shortened regimen. STREAM aims to generate evidence for shorter, more tolerable MDR-TB regimens, while improving local capacity to conduct clinical trials.

The evidence generated by STREAM is important for guiding policy-making at the international and national levels. To achieve maximum impact, trials must ensure that results are shared widely and effectively with all key stakeholders. However, dissemination of important research results is often limited to publication in peer reviewed journals, with far less effort made to inform key stakeholders, such as Ministries of Health, community stakeholders, and trial participants, about the results. Failure to involve key stakeholders in results dissemination can diminish the impact of important research findings by excluding key advocates of change.

 STREAM trial staff at B.J. Medical College in Ahmedabad, India participate in a webinar session about the STREAM Stage 1 trial results.

STREAM trial staff at B.J. Medical College in Ahmedabad, India participate in a webinar session about the STREAM Stage 1 trial results.

The STREAM trial is comprised of 2 stages. Stage 1 of the STREAM trial began in 2012 in Ethiopia, Mongolia, South Africa, and Vietnam and sought to determine whether the nine-month treatment regimen is no worse than the 20-month treatment regimen.  Preliminary results for Stage 1 were released at the 48th Union World Conference on Lung Health in Guadalajara, Mexico in October 2017. According to those preliminary results, the efficacy of the shortened, 9-month regimen is expected to be very close to the 20-24 month regimen. The nine-month regimen also reduces the number of pills a patient needs to take by approximately two-thirds, requires fewer visits to health facilities for treatment, and is cheaper for both the health system and patients.

Disseminating clinical trial results like the Stage 1 results is an ethical obligation for researchers and can greatly facilitate policy and program change. But, in practice, dissemination often fails to reach key stakeholders, and the logistics and technical challenges of disseminating complex findings can make the process challenging. In response, Vital Strategies’ Research Division designed a comprehensive results-dissemination strategy to ensure the Stage 1 findings reached all key stakeholder using appropriate communication channels and materials developed specifically for each key audience. The strategy encompassed five key steps to address the main stakeholder groups:

  • Sponsor dissemination to international health organizations, including the WHO
  • Sponsor dissemination to trial staff
  • Principal investigator dissemination to Ministries of Health and other national policy makers
  • Principal investigator dissemination to community advisory boards (CABs)
  • Principal investigators/CAB dissemination to participants and other community stakeholders

The STREAM dissemination process was impressive for both its impact and its reach.  At the international level, after release of the results and subsequent one-on-one discussions with Vital Strategies and MRC, the World Health Organization confirmed their earlier recommendation for use of the standard shortened regimen evaluated in STREAM, acknowledging the importance of STREAM’s contribution:

“We appreciate the significant work done by the [STREAM] study investigators to generate randomised controlled clinical trial evidence for the shorter regimen,” said Dr. Tereza Kasaeva, Director of WHO’s Global TB Programme. “Having evidence-based policies is key to improving care for patients affected by the global public health crisis of MDR-TB.”

At the national level, key stakeholders from all walks of life participated in STREAM events.  In Moldova, 176 participants from the Ministry of Health, Labor and Social Protection, the national TB Control Program, the State University of Medicine and Pharmacy “Nicolae Testemitanu”, the Municipal Clinical Hospital of Phthisiopneumology and others gathered at the STREAM trial site in Chisinau (the Institute of Phthisiopneumology “Chiril Draganiuc”) to hear Dr. Elena Tudor present the results.  In Mongolia, Bazra Tsogt, Trial Coordinator, presented the results to 96 participants from the national TB program and district MDR-TB treatment facilities at the National Centre for Communicable Diseases of Mongolia.

 Mongolia STREAM Trial team shares results with the National TB Program and district MDR-TB staff.

Mongolia STREAM Trial team shares results with the National TB Program and district MDR-TB staff.

Perhaps most importantly, STREAM dissemination reached those most affected by the illness – STREAM trial participants, their families and local community members.  In all, more than 473 trial participants and community stakeholders gathered at large community celebrations where their participation in the trial was acknowledged and where they learned about the results from STREAM principal investigators and community advisory board members.

 Principal Investigator at St. Peter’s Hospital, Addis Ababa presents results to participants and community stakeholders

Principal Investigator at St. Peter’s Hospital, Addis Ababa presents results to participants and community stakeholders

Results dissemination should be inclusive and involve all affected stakeholders. It creates opportunities for building long-term relationships between researchers and local communities, and for better understanding of the needs and capacity for MDR-TB research in those communities. Ultimately, dissemination is the first step to generating policy and program change, and will help legitimize changes made in response to trial results.

The STREAM Clinical Trial was initiated by The International Union Against Tuberculosis and Lung Disease (The Union).  The trial represents a unique collaboration between USAID, Janssen Pharmaceuticals, The Union and The Union’s affiliate, Vital Strategies, and aims to generate evidence regarding the effectiveness of shorter, more tolerable treatment regimens for MDR-TB.