When the World Health Organisation (WHO) declared the COVID-19 pandemic on 11th March 2020, countries the world over implemented restrictions to manage this accordingly. As well as challenges faced by people and communities around the globe, the pandemic presented unique challenges for the clinical trials community, with many existing studies being either temporarily paused and / or adapting their process.
Interim analysis provides several options and opportunities for sponsors, including modifications of the trial design and adaptive designs, monitoring the safety of the trials with DSMB’s, post marketing surveillance and long-term follow up and monitoring if the trial is going to go ahead as originally intended (i.e. sample size). The statistical output for an Interim Analysis may include (but is not limited to) tables, figures and listings, data listings, interim study reports, IDMC and DSMB requirements. The Interim Analysis may be blinded, partially blinded, unblinded, or will use a “dummy” randomisation schedule.
FSP (Functional Service Provision) is fairly common in the United States and Europe, where many of the world's leading pharmaceutical and biotechnology companies are located, but the term ‘FSP’ is not yet commonplace in Japan. Furthermore, FSP is not ‘mainstream’ in China either. Japanese-based pharmaceutical companies, including foreign companies, are mainly utilising a more orthodox model of outsourced services (more commonly known as a ‘Full-Service Model’). In Japan, in-house statisticians often create statistical analysis plans and protocol statistics sections and only outsource the programming elements of their statistics-related work. In addition to this, there are many temporary staffing companies which provide personnel to companies to support their daily programming work. The US and Europe also oftentimes operate an “enhanced FSP” – building teams of high calibre technical expertise and experience, working under the direction of a technical lead.
In Europe and the United States, FSP is already well known and well utilized. In Japan, the workforce landscape is markedly different - it is difficult to hire experienced statisticians and analysis programmers’ who are mid-career, it’s difficult to dismiss full-time employees in Japan, and it is difficult to secure hiring quotas for full-time employees. In the future, it will be possible to respond more flexibly than dispatching, as the work of clinical testing and statistical / analysis programming becomes more complicated and specialized, awareness, benefits and demand of FSP will gradually increase.
An IDMC (sometimes known as a DMC/DMEC/DSMB) is an Independent Data Monitoring Committee, whose role it is to monitor the conduct of a clinical trial, to ensure the safety of its participants and the scientific integrity of the study. By periodically reviewing the accumulating safety, and sometimes efficacy data, the IDMC will make recommendations on the continuation and management of the study.
The IDMC is an independent committee with a Chair, made up of two or more disease-specific experts and at least one statistician. They are usually governed by an IDMC charter, which outlines their role and responsibilities, the study data to be reviewed, any stop-go criteria, and IDMC quorum and voting rights.
Here in England, everyone can now be given two lateral flow tests a week to test if they have COVID-19, in an extension of the government’s testing programme. Lateral flow tests (LFTs) are rapid tests and are convenient as they can give a result in around 30 minutes and don’t require a laboratory. They use a swab of the nose and/ or throat and the testing kit itself is a small plastic device, similar to a pregnancy test. They are intended for picking up additional infected individuals who may otherwise have been missed because they don’t have any symptoms. LFTs have been used in schools since they reopened and have caused quite a bit of controversy as it is known that LFTs are not as accurate as polymerase chain rection (PCR) tests. PCR is the most accurate test for COVID-19 infection and if a symptomatic person has a positive PCR test, this is likely to accurately indicate infection. For the purposes of the remainder of this article we shall assume that a positive PCR test corresponds to a true positive and a negative PCR corresponds to a true negative.