Years ago, I spent several months painfully developing a mathematical prediction model to evaluate decreases in cervical cancer prevalence assuming introduction of papillomavirus vaccination in a developing country with different sexual mixing patterns1. The project required collaboration with virologists, social epidemiologists, and mathematicians as is often necessary when constructing epidemiological models reliant on biological, social, and statistical factors, among others. Along the way, I gained a strong appreciation for the complexity of these models, but also that every model depends upon assumptions laden with variability and uncertainty. Beginning as early as December 2019, reports surfaced about clinical cases in Wuhan, China of a new disease, later termed COVID-19, due to infection with a novel coronavirus, SARS-CoV-2. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic2 at a time when there were 118,000 cases in 114 countries. Now, by May 28, 2020, there are over 5.8 million COVID-19 cases contributing to more than 360,000 deaths in 213 countries and territories3. In a scramble to understand the pandemic’s trends and trajectories, several epidemiological models have been developed aimed at predicting or forecasting COVID-19 cases, burden on the healthcare system, and overall mortality, given assumptions and available information. One might ask, why so many models producing different results? The aim of this paper is to summarize the key concepts and types of epidemiological models, why they are useful and limitations.
In response to the COVID-19 pandemic, many companies have taken steps to enable all of their employees to work from home. In addition to any existing home working procedures, further investments in to infrastructure and server capabilities should be considered, to ensure uninterrupted, effective home working for all employees, be that in a small company or a worldwide business such as PHASTAR’s. For example, PHASTAR’s IT department has provided additional support to staff through many avenues including VPN access, client system access and hardware in order to ensure that all staff can all provide the same level of support to our clients and their needs.
Whilst some employees may have been working from home for many years, it ought to be recognised that this will be a new experience for many others. From PHASTAR’s perspective, we are proud of the way that our team has risen to the challenge and continue to support clients without any interruptions to service or delivery – even recently completing a project ahead of schedule!
Clinical trial research is a fast-paced industry whereby the requirement to bring lifesaving and life changing drugs to market quickly, to meet patients needs, is a constant driver to looking for time saving innovations. As a result, pharmaceutical companies are frequently looking for ways to expedite clinical trial set up and execution while maintaining regulatory compliance and data quality.
At PHASTAR, we provide tailor made EDC solutions for our clients that will allow rapid set up and deployment, partnering with our EDC partners Medrio and Medidata to achieve this. During the contracting phase of a new study, importance is placed on actively engaging our partners and clients in exploring solutions for data capture that will ensure efficient database set-up, short timelines and quality data collection. For example, innovative and flexible forms to support long-term observational studies where data collection may vary between subjects depending on the local healthcare provider, ensuring flexibility while maintaining quality.
During a pandemic, data collection is of the upmost importance to be able to control and stop the spread of disease. It is essential to have adaptable, available data systems with clear, simplified forms that can be completed off-line and these systems must be operable both on and off network to enable field workers to complete the fields while working in remote locations and then later upload the data to a repository when there is network access. Overall, a solid IT system is necessary for quick capture and relay of information.
Another challenge during an outbreak response is creating and disseminating effective and timely information to the public. This requires a full understanding of the knowledge, attitudes and beliefs of the target audience. Target communication needs to account for the local level of understanding and literacy while being culturally appropriate. There needs to also be a way of monitoring if the communication is effective, again this needs to be done in real time. It is vital that communication is simple, consistent and reliable.
The current COVID-19 pandemic has seen a large increase of data systems and other forms of communication. Furthermore, there are a huge number of clinical studies ongoing or in the pipeline to address this crisis. Moving forward, a central repository housing essential information (e.g. trial protocols and analysis plans, interim findings, and real-time reporting of primary results) on completed and ongoing clinical trials will be needed, in order to encourage collaboration and information sharing, as well as to avoid any redundancy in research efforts.
In the later stages of 2019 and the beginning of 2020, the Coronavirus pandemic began spreading across the world and it became apparent that it would affect so many areas of how we live our lives, from children attending school, working in our offices and being able to shop freely. Since before the lockdown began in the UK on the 23rd March, there have been restrictions put in place at clinical trial sites to protect their patients includingrestricting unnecessary visitors (such as CRAs) to site.
Guidance documents on how to conduct clinical trials during the COVID-19 crisis have been published by regulators, providing guidance on (among other areas) what considerations should be made regarding the collection of any data relating to COVID-19 interruptions, the impact of missing data and data collected outside the protocolled time window.
The guidance says to capture specific information in the case report form that will explain the basis of the missing data, including the relationship to COVID-19, for missing, protocol-specified information, e.g. from missed study visits or study discontinuations due to COVID-19. This information, summarised in the clinical study report will be helpful to the sponsor and FDA.
Taking the guidance in to consideration, we quickly developed a CRF page to capture the COVID-19 interruptions on the data including accounting for missing visits, missing assessments, delayed visits and assessments and other impacts on the data due to COVID-19. The guidance is that COVID-19 interruptions should be detailed in the clinical study report (CSR), and so we have developed a data collection tool to capture this data. This CRF page was available to show our clients within days of the guidance being issued.
We have also helped a client develop an alternative process, without the use of this eCRF, through using queries to identify missing data affected by COVID-19 and subsequently those query results will be used to identify protocol deviations caused by COVID-19. Collecting the COVID-19 interruptions as protocol deviations seems to be the solution of choice for Sponsors of clinical trials which are already well established. There are slightly increased risks with this solution compared to using the eCRF page however, these risks have been addressed and a process put in place.
Following a communication released by ICH M1 Points to Consider Working Group and MedDRA MSSO on Coronavirus (here), we created some text to be added to our coding document so that our individual study guidelines cover the coding of the coronavirus related medical terms - at that point COVID-19 specific terms were not available in the MedDRA version 23.0 regular release which took place in March 2020. The MSSO subsequently re-released MedDRA v23.0 in April which included new COVID-19 related terms and revisions -this is a replacement of the regular March release. Where appropriate, MedDRA has been up-versioned to V23.0 in our studies. Our coding documents have been updated to reflect any up-versioning of MedDRA and instruction on coding of any COVID-19 related terms.
We are closely following Coronavirus updates from WHODrug. Currently there are no plans to re-release the March 2020 version of WHODrug Global but if those plans change, we are ready to implement in the same way that we have done for MedDRA. Currently novel COVID-19-related medicinal products (for example, new molecular entities and new vaccines) are being included in the dictionary ready for the next release in September 2020.
We have been working closely with our clients to support and advise on discussions regarding changes to data collection e.g. remote visits, options regarding using ePRO and changes to our processes to support data cleaning whilst CRAs cannot attend site. Risk-based monitoring options can also be used increasingly so that we can continue to ensure a high standard of data collection and reporting.
At PHASTAR, our data management team control and implement the database design on our projects and therefore we have been able to provide a fast turn-around of database amendments to support adjustments to data collection e.g. applying the new CRF page for capturing COVID-19 interruptions, adding information to individual forms regarding reasons for non-collection or delay. We continue to work with our clients to help them manage the changes for their specific trials using the information we have gained from the various industry guidance and discussions currently taking place. If you would like more information, please don’t hesitate to get in touch.
