The Solidarity trial for treatments is a multinational Phase III-IV clinical trial organized by the World Health Organization and partners to compare four untested treatments for hospitalized people with severe COVID-19 illness. The trial was announced 18 March 2020, and as of 21 April, over 100 countries were participating. In May, the WHO announced an international coalition for simultaneously developing several candidate vaccines to prevent COVID-19 disease, calling this effort the Solidarity trial for vaccines.
Solidarity trial for treatment candidates
The trial intends to rapidly assess in thousands of COVID-19 infected people the potential efficacy of existing antiviral and anti-inflammatory agentsnot yet evaluated specifically for COVID-19 illness, a process called "repurposing" or "repositioning" an already-approved drug for a different disease. The Solidarity project is designed to give rapid insights to key clinical questions:
Do any of the drugs reduce mortality?
Do any of the drugs reduce the time a patient is hospitalized?
Do the treatments affect the need for people with COVID-19-induced pneumonia to be ventilated or maintained in intensive care?
Could such drugs be used to minimize the illness of COVID-19 infection in healthcare staff and people at high risk of developing severe illness?
Enrolling people with COVID-19 infection is simplified by using data entries, including informed consent, on a WHO website. After the trial staff determine the drugs available at the hospital, the WHO website randomizes the hospitalized subject to one of the trial drugs or to the hospital standard of care for treating COVID-19. The trial physician records and submits follow-up information about the subject status and treatment, completing data input via the WHO Solidarity website. The design of the Solidarity trial is not double-blind - which is normally the standard in a high-quality clinical trial - but WHO needed speed with quality for the trial across many hospitals and countries. A global safety monitoring board of WHO physicians examine interim results to assist decisions on safety and effectiveness of the trial drugs, and alter the trial design or recommend an effective therapy. A similar web-based study to Solidarity, called "Discovery", was initiated in March across seven countries by INSERM. The Solidarity trial seeks to implement coordination across hundreds of hospital sites in different countries - including those with poorly-developed infrastructure for clinical trials - yet needs to be conducted rapidly. According to John-Arne Røttingen, chief executive of the Research Council of Norway and chairman of the Solidarity trial international steering committee, the trial would be considered effective if therapies are determined to "reduce the proportion of patients that need ventilators by, say, 20%, that could have a huge impact on our national health-care systems."
Adaptive design
According to the WHO Director General, the aim of the trial is to "dramatically cut down the time needed to generate robust evidence about what drugs work", a process using an "adaptive design". The Solidarity and European Discovery trials apply adaptive design to rapidly alter trial parameters when results from the four experimental therapeutic strategies emerge. Adaptive designs within ongoing Phase III-IV clinical trials - such as the Solidarity and Discovery projects - may shorten the trial duration and use fewer subjects, possibly expediting decisions for early termination to save costs if interim results are negative. If the Solidarity project shows early evidence of success, design changes across the project's international locations can be made rapidly to enhance overall outcomes of affected people and hasten use of the therapeutic drug.
Treatment candidates under study
The individual or combined drugs being studied in the Solidarity and Discovery projects are already approved for other diseases and recognized as safe. They are:
Due to safety concerns and evidence of heart arrhythmias leading to higher death rates, the WHO suspended the hydroxychloroquine arm of the Solidarity trial in late May 2020, although reinstated, then withdrawn again when an interim analysis in June showed that hydroxychloroquine provided no benefit to hospitalized people severely infected with COVID-19.
Support and participation
During March, funding for the Solidarity trial reached million from 203,000 individual donations, charitable organizations and governments, with 45 countries involved in financing or trial management. As of April 2020, the countries participating were Argentina, Bahrain, Brunei Darussalam, Canada, France, Indonesia, Iran, Malaysia, Myanmar, North Korea, Norway, Philippines, Portugal, South Africa, Spain, South Korea, Switzerland, and Thailand.
The WHO has developed a multinational coalition of vaccine scientists defining a Global Target Product Profile assess the development of the most promising candidate vaccines; 2) map candidate vaccines and their clinical trial worldwide, publishing a frequently-updated "landscape" of vaccines in development; 3) rapidly evaluate and screen for the most promising candidate vaccines simultaneously before they are tested in humans; and 4) design and coordinate a multiple-site, international randomized controlled trial the Solidarity trial for vaccines to enable simultaneous evaluation of the benefits and risks of different vaccine candidates under clinical trials in countries where there are high rates of COVID-19 disease, ensuring fast interpretation and sharing of results around the world. The WHO vaccine coalition will prioritize which vaccines should go into Phase II and III clinical trials, and determine harmonized Phase III protocols for all vaccines achieving the pivotal trial stage.
