While the global pandemic has caused myriad formidable challenges for clinical trial teams, the continuing demand for new therapies means researchers must look for ways to prevent interruptions and cancellations. Outsourcing-Pharma (OSP) recently spoke with Deepu Joseph (DJ), vice president and global head of clinical data management with Quanticate, about the unprecedented obstacles the virus has caused, and how researchers can harness technology to tackle them.
OSP: Could you please tell us a bit about Quanticate—who you are, what you do, key specialties and what sets you apart from the competition?
DJ: Quanticate is one of the world’s largest global data-focused clinical research organizations (CROs) with a primary focus on data capture, statistical analysis, and clinical trial reporting. As an expert in clinical data, Quanticate can rapidly provide high-quality teams that offer a number of flexible solutions; service areas include clinical data management, biostatistics, statistical programming, pharmacokinetic/pharmacodynamic (PK/PD) analysis, medical writing, and statistical consultancy.
Quanticate meets the needs of drug and device development companies by offering customer focused resource solutions from fixed cost or functional service provider (FSP) models through to consultancy. Quanticate has become the trusted supplier of choice for many companies from niche biotechnology and device companies to top tier pharmaceutical giants.
OSP: Please provide an overview of the evolution in data capture and trial reporting in the time leading up to COVID-19.
DJ: Data capture had been evolving prior to the COVID-19 pandemic, driven by the pressure on drug developers from two fronts. Firstly, the increasing costs of drug development result in innovations that aim to reduce costs in trials via improved methods of data capture that can be done remotely and more efficiently.
Secondly, the industry has realized that a more patient centric approach to clinical trials is needed to increase enrolment, reduce missing data or participant drops outs, and ensure overall patient experience is thought of. Improved patient centricity reduces the burden on patients involved in clinical trials and helps drug developers extract more accurate and real time data for the trial,
Patient-centric solutions help collect real time data (eg; eRecruitment, eConsent, ePRO, Televisits, etc); this helps risk assessment and effective risk-based monitoring implementation from a patient safety perspective. All these solutions can be integrated (thanks to new age technologies) and thus we don’t need to do traditional periodic data acquisition which takes away the real time aspects.
Clinical trial reporting has also been evolving. There is now more focus on statistical programmers requiring knowledge and skills in alternative programming techniques to support improved efficiency and improved timelines.
The industry is seeing more innovations and automation skills are highly desired. Programmers are now using more than the industry standard of SAS as they look to programming R for alternatives and upskilling themselves in phyton to support demands for machine learning (advanced automations).
OSP: How did COVID-19 impact the trial industry in the time immediately after its arrival, in the months since?
DJ: The natural evolution of data capture and trial reporting had positioned the industry well to a certain degree as COVID impacted trials. Virtual/decentralized trial solutions were being adapted very slowly before the pandemic, mostly on less interventional studies or treatments being trialled.
The pandemic forced the industry to further explore these methods as a must to ensure drug developers can maintain their studies as these solutions have enabled certain trials to adapt and continue.
A great example of this is uptick in remote source document verification (RSDV) and remote monitoring, due to the travel restrictions and social distancing aspects of COVID-19. The demand for RSDV and remote monitoring has increased tenfold as challenges occur in sending clinical research associates (CRAs) to site to validate source data. The ability to do this remotely, and direct the CRAs/monitors centrality instead of visiting every site reduces the travel costs, but with travel restricts have supported the continue monitoring of trials in this difficult period.
OSP: Specifically, how has the pandemic impacted patient recruitment and retention?
DJ: Patient recruitment and retention has been problematic. With lockdowns, travel restrictions and other state rules across the globe, it’s a challenge to partake in the necessary requirements of being a trial participants. Many patients enrolled in studies have also fallen ill with COVID-19 or been in close contact with someone who’s had COVID and had to self-isolate and been unable to provide data readings due to missing visits.
Also many drug developer recognized the unnecessary risks of continuing a clinical trial during a global pandemic for non-life threatening medicines. Trials have been put on hold where needed.
However, not all trials have been placed on hold and in more serious conditions, the is still a need for patients to support the clinical trial system. This is where the innovations in data capture and monitoring have given drug developers some hope as certain trials can continue to a certain degree.
It is vital that a trial that is adapting to COVID-19 consults with a biostatistical consultant as their foresight can help rescue an existing trial that may be impacted by covid-19 and patient retention, or support in designing a new trial with all the new technologies and potential reduced patient sample size to see demonstrate an INDs safety and efficacy.
OSP: Could you share some insight about trial interruptions?
DJ: Analysts who explore the data on www.ClinicalTrials.gov noted an increase in trial suspensions in March and there have been many instances where trials have been delayed, but few have actually been cancelled.
For trials that have commenced, regulators have been supportive, some have even skipped site visits actively encourage remote monitoring to reduce travel and exposure. For trials that have not yet commenced, drug companies are often delaying recruiting in anticipation that sites will eventually reopen and patients can be recruited at that time.
There is no question that the pandemic significantly disrupted the clinical trials industry but it hasn’t halted the search for new drugs or the business of pharmaceutical outsourcing. Sponsors will continue to increase their use of technologies to enhance the efficiency of trials after the pandemic recedes, and regulators around the world will likely remain flexible about accepting those developments.
OSP: Do you think the clinical research industry will be permanently impacted?
DJ: The demand for reducing drug development costs and improving patient centricity has always been there. The evolution of data capture, trial reporting and monitoring of trials support will continue in a post COVID-19 world as the pharma industry looks to embrace the latest technologies and make life easier for everyone involved through the natural demands of innovation.
I don’t think the industry will be permanently impacted by COVID, but the industry is shifting to a more patient-centric approach as well a decentralized approach to clinical trials. This will permanently impact the industry in positive ways, COVID has been catalyst to help support this change.
OSP: How has Quanticate weathered the storm, and helped clients do the same?
DJ: Quanticate has been operating well and all employees have been working from home. Where some clients may have placed trials on hold, others are seeing an increase in demand.
Our data focused niche positions us well to handle the challenges of the pandemic. With expertise in using the latest data capture technologies and industry-recognized statistical knowledge, we have been able to design and support trials in the COVID era. We have been involved in rescuing trials in jeopardy or ensuring a trial can still prove its hypothesis with limited patient samples or ensuring that data is still collected via patient centric devices.
As well as the data capture and design, we have made advances in clinical trial reporting, with automation and knowledge on alternative programming techniques, as well visualization which ensure sponsors can receive insights and outcomes much faster. Finally with solutions like our RSDV platform, centralised statistical monitoring, and risk based approaches to monitoring, we can ensure that study data is validated verse source effectively despite the global travel challenges we all face.
OSP: What will trial professionals need to do to “pandemic-proof” their operations going forward?
DJ: Implementation of risk-based monitoring with appropriate risk assessments that consider the newer risks posed by the pandemic would be key to bringing efficiency of overall trial conduct along with taking care of patient safety and generating quality data. As the above could be enhanced by enabling more real time data acquisition using various data collection tools, devising a larger data collection strategy with a data expert would be key.
Using remote data collection tools for trial conduct like eCOA, televisits, eConsent etc along with centralized monitoring driven by techs supporting rSDV etc. could help being more patient centric. This improves patient recruitment statistics, their adherence to trial protocol and reduces dropout rates thus resulting in more patient engagement and data quality.
Clinical trials will face several statistical challenges in the foreseeable future. We can expect an increase in missing patient visits, which will affect the values and data points of ongoing trials; this can potentially lead to a failed regulatory submission as there is not enough data to demonstrate the drug’s safety or efficacy. Knowing how to handle missing data in clinical trials as well as estimands will be important to overcome these challenges.
To navigate the difficult road ahead, clinical trial sponsors should consider sample size recalculations so that less patients need to be recruited and risk levels are lowered. An early unplanned interim analysis, which is a prediction of whether a trial is succeeding or failing in its objectives based on current data collected, can also be performed, though engagement with regulatory agencies would be critical; failing trials could be stopped sooner to reduce patient risks and successful trials could find ways to prove drug efficacy with less clinical visits or data using sample size recalculation methodologies.
All of this will require an ongoing review of the protocol and solid statistical knowledge to amend previously approved study procedures, as well as medical writing skills to ensure changes are correctly documented to regulatory standards.
Clinical research associates are currently unable to travel to sites and remote monitoring has become a more viable solution during this time. This leads to the potential to move away from 100% rSDV and recent European Medical Association (EMA) guidance released in April 2020 highlights how sponsors and CROs may wish to use rSDV to effectively monitor clinical trials, without sending monitors/CRAs to site and ensuring trial conduct and sites follow study protocol.
It would be beneficial for sponsors and CROs to use centralized statistical monitoring to discover underlying data issues which a CRA may miss when using traditional on-site monitoring. Erroneous data can be identified more easily to help prepare for regulatory submissions in these challenging times.
OSP: Do you have anything else to add?
DJ: Quanticate being a data-focused CRO is rightly placed to support pharma companies in developing the overall data collection and reporting strategy during and beyond the pandemic times. Our deep understanding of the data flow possibilities, partnerships with major tech players, 25-year-strong statistical and programming legacy and the flexibilities we can offer as a data focused expert can easily accommodate tailored solutions to varied needs of specific clinical protocols or development programs.