Crises are rare periods in history when need stimulates the search for innovative solutions and accelerates the timing to start adopting them. Given the enormous investments that the life sciences industry makes in drug development, it is not surprising that traditionally the adoption of innovative approaches and processes is rather slow.
But the COVID-19 pandemic has changed everything.
In fact, in the world of clinical research, a significant paradigm shift is taking place as more and more CROs, and pharmaceutical companies are considering alternative ways of conducting clinical trials (e.g., siteless, digital, virtual).
The side effects of the pandemic: lights and shadows
The COVID-19 pandemic has generated unprecedented negative consequences in conducting clinical trials and is presenting unique challenges to the entire ecosystem of clinical research and healthcare.
“I think the pharmaceutical industry is at an Inflection Point,” says Mary Varghese Presti, VP, Life Sciences, Watson Health at IBM. “The impact of COVID-19 on the health care system, in general, will serve as an unintended catalyst for change in the pharmaceutical industry. Health care systems are at their maximum capacity. There are concerns about the safety of patients and health workers. So, suddenly there is a situation where, if clinical research is to progress, we need to start looking for alternative ways of doing so. And the technology is there ready to do it”.
Clinical studies started before the pandemic, have been amended or discontinued in large numbers, those ready to begin temporarily suspended. In contrast, the scientific community and regulatory authorities have rushed to start clinical trials for potential new COVID-19 treatments, many of which were conducted in derogation of the principles of clinical research methodology and good clinical practice rules.
The anxiety and pressure to rapidly obtain data and evidence on the efficacy of the various treatments proposed for pandemic treatment and prevention have led to the activation of many studies of low clinical value, without comparison groups, with uncontrolled data and contradictory results that generate false expectations in public opinion and policymakers.
In an attempt to preserve certain minimum quality requirements, both the FDA and the EMA have recently loosened their regulations and encouraged promoters to take advantage of digital technologies that have a positive impact on both the study conduct and patient safety.
Preserving patient study participation and safety has become imperative
In a survey launched on March 26, 2020, Greenphire, a provider of financial solutions for clinical trials, asked the staff at experimental sites around the world how their activities had been affected by the pandemic. 70% of the 1,700 respondents indicated that to support patients who cannot reach the clinic due to social distance, they are leveraging technology to control patients at home (virtual visits/telemedicine).
Designing a study “patient-centric” has never been as imperative as it is now. For example, patients using ePRO systems are more likely to participate in a study and adhere to the required procedures if they can use their own devices (e.g., a BYOD approach). It is not enough to define which parameters to measure and through which device. It is equally important to understand how a patient interacts with the equipment and how these activities fit into their daily life.
Patients expect this technology to be as easy to use and generate the same experience as when, for example, they make a video call, order a product via the internet or record their daily movement data from a device.
The post-pandemic value of digital and virtual studies: increasing the use of technology to reduce site visits
The technological solutions used during the pandemic for urgent mitigation or contingency purposes, raise the option of their regular use even in a post-pandemic world to overcome the current model of clinical trial execution that is anchored to the clinical site and periodic on-site visits for patients and monitors.
As discussed above, in many cases, follow-up visits at the site can be easily replaced by remote patient’s monitoring using telemedicine platforms, while the traditional on site-monitoring can be replaced by a the virtual monitoring visit during which both the source data at source and the site file documentation and finally the status of the IMP can be verified.
As far as the remote source data verification (rSDV) is concerned, also according to the guidelines issued by EMA and FDA, this is possible if a series of conditions regarding both the security of the digital platform used and the respect of the patient’s rights are fulfilled. In particular:
- rSDV should focus on quality control of critical data, such as primary efficacy and safety-relevant data.
- rSDV of patient hospital records in the European Union can only take place from a (remote) monitoring location within the Union, without any connection to third countries.
- The promoter should consult its Data Protection Officer (DPO) and the principal investigator (PI) in each site to determine whether remote rSDV is feasible and manageable for this site and what the practical aspects might be.
- The study promoter or CRO if the owner of the rSDV platform, must have both a specific SOP in place and if under the GDPR regulation, also a Data Protection Impact Assessment document (DPIA) to describe the impact on data protection during remote verification of patient’s clinical data.
- If the principal investigator, in consultation with the site data protection officer, consents in writing to the rSDV. Before proceeding, this procedure must be approved by the Ethics Committee and the Competent Authority, if required. Therefore, it is recommended that this procedure is also described in the “monitoring” section of the study protocol.
- The possibility to use the rSDV modality must also be clearly stated in the informed consent form regularly signed by the patient before being enrolled in the study.
- Site staff and monitors must be adequately trained in the remote SDV process.
- Site staff should create pseudonymized copies and mask any confidential information that is unnecessary and unrelated to the study. Copies should then be certified electronically, as required by the GCPs.
- The execution of the remote SDV by the site’s monitor must take place in a concise time (3-5 days max) and must rule out the possibility of downloading or printing the documents
- The rSDV application must be validated according to GCPs and CSV requirements; it must have an audit trail, use a secure internet connection and have access control.
- At the end of the remote source data verification activity, and after the monitor has deleted the pseudonymized documents, the system must generate a certificate stating that the documents have canceled. This certificate must then be archived in the site file.
- When the monitor goes to the site for a traditional on site-monitoring visit, it must verify that the documents controlled during the rSDV are actually those related to the study participant with the code provided.
The implementation in the study of an electronic document system (eTMF/eISF) allows the remote control of documents continuously and regularly regardless of the monitoring visit to the site, thus ensuring a level of completeness and accuracy of the file, impossible to achieve with a traditional approach.
Finally, the distribution, assignment, accountability, and compliance to the IMP is also possible remotely through appropriate digital platforms.
The evolution of decentralized clinical trials
As more technologies have proven to be effective and approved for use in clinical trials, the industry is likely to focus more on decentralized study models that allow for remote procedures and visits.
Regulatory authorities also envisage this scenario. In a statement in January 2019, the former FDA Commissioner, Scott Gottlieb, M.D., said: “Pragmatic and hybrid clinical trials, including decentralized studies incorporating real-world data (RWD) – can help clinical trials become more agile and efficient by reducing the administrative burden on promoters and trial managers, and can allow patients to receive planned treatments from providers close to their home without compromising the quality of the trial or the integrity of the data being collected”.
Data, of course, are at the center of clinical trials. But simply having more data is not the solution. Data are only valuable if you have the technologies, processes, and systems that can use them to reduce development time and costs. You need to manage the data and analyzes them in real-time in an inferential and predictive manner. Updated metrics allow a Risk-Based and Data-Driven approach in study management. Visualization of data, while the study is running, is a suitable and efficient way to see and understand trends, outliers and data models and to make appropriate decisions.
Only Advanced Analytics and Machine Learning enable you to take full advantage of the value of large amounts of data from multiple sources and make digital or virtual clinical trials faster, more patient-centric, higher quality, and less expensive.
Finally, we must be aware that digital and virtual studies and advanced analytics are not a goal for the future but a concrete reality now with a solid proof of applicability, generalizability, and significant benefits.