This article is the second part of our white paper: Top eClinical Trends in 2016. Read the first part here. Please visit clincapture.com/papers to download the full report and access more white papers.
Glenn Keet is CEO at ClinCapture. He has worked in healthcare IT for over two and a half decades, and most recently was responsible for Business Development on the Optum Health Care Cloud, focusing on developing the ecosystem of providers, developers and consumers. Mr. Keet became part of Optum via the acquisition of Axolotl Corp., where he was President. He co-founded Axolotl in early 1995. Prior to his role as President, Mr. Keet was EVP over Sales and Marketing, responsible for all HIE sales to states, RHIOs and hospitals. Glenn Keet has previously held the role of VP of Business Development, and also has served as VP of Professional Services. He was the company’s Product Manager until 2001.
Changes in RBM Trends
Recent trends in risk based monitoring (RBM) were discussed at the November 2015 CBI Conference on risk based trial management. RBM is the practice of saving time and money by reviewing or verifying only a portion of the source documents, those most likely to have the greatest potential to affect the study data. Among the topics were the changing roles of study monitors, as well as the way RBM is changing how clinical trials are conducted. Even though some CRO and sponsors aim for 100% SDV, the path to RBM has been forged with many new technology companies addressing RBM in the last couple of years.
Recent trends indicate that sponsors are more comfortable than ever outsourcing source data verification and monitoring visits to CROs. However, they now prefer to insource Clin Ops and data management so they can have more real-time control over the study, and mitigate any fallouts as they happen.
The FDA recently developed a risk-based site selection tool which collects NDAs by clinical investigator sites and allows the agency to use the stratified data in order to select sites for GCP inspections .
Experts point out that as more companies employ RBM, clinical trial teams should differentiate between clinical data supporting safety endpoints, efficacy endpoints, protocol endpoints, performance, and general study management . The value of RBM would not be leveraged if all data would otherwise be treated equally instead of being classified.
Another useful piece of advice is to pay attention to data trails and the changes made, having 100% QC on any modifications. The recent trend in higher RBM adoption has adapted the monitoring role to keep track of any changes the study team and sites are making. Experts say that is the way for people, processes and technology to complement each other when using RBM in a clinical trial.
The FDA defines electronic consent as “using electronic systems and processes that may employ multiple electronic media (e.g., text, graphics, audio, video, podcasts and interactive web sites, biological recognition devices, and card readers) to convey information related to the study and to obtain and document informed consent” .
There are several eSignature and eConsent systems currently available on the market. In addition, companies such as Apple are also entering the medical research market with apps and wearable technology. For example, Apple’s ResearchKit has a module for building electronic consent forms.
A recent survey of the top 50 pharma companies shows that about 66% of them are either using eConsent or planning to in the near future. The percentile is even higher among the top 25 companies on the list- 88% of them have implemented eConsent. 100% of the top ten companies have also put eConsent initiatives in place .
ePRO to Replace Paper Soon
Technology is also placing the patient at the epicenter of clinical research, particularly with electronic patient reported outcomes (ePRO) systems allowing patients to report clinical trial data themselves. The modern ePRO systems are designed to maximize the ease with which patients report their observations. Additionally, they better integrate with eClinical systems to capture and direct relevant clinical data faster to clinical teams. ePRO systems integrate with electronic data capture (EDC) systems to automatically and securely import clinical data from the ePRO directly into the EDC system. This allows a quicker response time in the case of adverse events, for example.
In a recent survey, examining 22 sponsors and CROs, 18 reported having adopted ePRO which resulted in increased data quality, patient compliance and efficient data collection. 61% of the surveyed companies indicated they implemented ePRO in the last five years, 28% in the last 10 years, and 11% over 10 years ago . Experts say the increased emphasis placed on patient reported outcomes and the push for technology adoption in clinical trials has resulted in significant increase in ePRO utilization. While the Tufts survey points out there’s been an overwhelming increase in ePRO usage in the oncology field, the main drawback cited has been the cost of using ePRO as compared to paper.
Yet, it has long been known that ePRO improves the quality of the patient reported data over paper systems or diaries; patients, being human, often don’t write down their notes as they should each day or in a timely manner. Not only can ePRO systems remind patients to record their notes, but can also track whether the patient created all their entries at once just prior to the next site visit, as is often the case in the paper world (aka the parking lot syndrome). The higher ePRO adoption trend is likely to continue as more companies see its value for post-marketing trials, as well as its benefits and expanding capabilities as new vendors add systems each year.
With increased regulatory requirements and the trend towards personalized medicine, sponsor companies and CROs need to access more specific solutions to meet their need, making systems integration an increasing necessity for a successful clinical trial. In addition, risk management during the product’s life cycle includes investigators, regulators and patients; requiring systems integration to ensure data is accurate and consistent.
Leveraging technology to optimize speed, quality and cost of clinical trials is a big hurdle for pharma and their CRO partners. Bringing drugs and medical devices to market faster is most important for business success. CROs are quickly realizing that in order to remain competitive, they need the IT infrastructure to accommodate an influx of clinical data that would be well-organized and easily accessible from a central repository.
This repository should handle the integration, reporting, management, visualization and analysis of all clinical data. For example, an integrated system, comprised of custom CTMS, Pharmacovigilance, EDC and a CDISC-compliant data warehouse enables the timely analysis of clinical data. Traditional integration between electronic data capture (EDC), clinical trial management systems (CTMS), clinical data repositories (CDR), clinical data management systems (CDMS) and statistical analysis systems (SAS) may require a lot of manual data tranformation. While many sponsors can afford to transcribe data in the right format before sending it to their CROs, smaller companies still struggle to prepare their data for FDA submission.
That is why integration is crucial for both clinical trial sponsors and CROs to exchange data during all trial phases. Big pharma reportedly spends close to $200 million annually for data transfer. But new trends are emerging to combat the old ways of not transferring data until all collection is done. More and more trials are now conducted with the data moving earlier during study conduct. This method allows managers to spot and ferret out potential problems, thus saving money and time. Another trend which saves time and money is following the CDISC’s (Clinical Data Interchange Standards Consortium) CDASH (Clinical Data Acquisition Standards and Harmonization) data standards for collection fields. This saves companies from not having to restructure their data in the drug-approval process. CROs must also follow data aggregation formats such as STDM (Standard Data tabulation Model).
Whether you choose EDC & CTMS, eTMF & Safety, or EMR integration, there is no one-stop-shop solution. For example, CTMS solutions such as Advanced Clinical Software’s Study Manager have been installed at over 2,000 sites but there are still no defined metadata and communication standards that allow CTMS and EDC solutions to share data. Many EDC systems have incorporated tools that render CTMS unnecessary for less complex trials, but a common issue with EDC-CTMS integration occurs when there are complex investigative site business practices. Many EDC systems only capture clinical trial data through eCRFs that lack CTMS information. Another issue is that some EDCs may lack timeline planning features such as reaching target subject recruitment milestones. As for eTMF & Safety integration, a common issue is the lack of real-time inspection and ICH/GCP compliance.
One way for improving this process is to focus on data analysis, not just warehousing it. Most companies only focus on front-end integration without considering the need to generate reports for regulators later. If data were integrated from the start, it would be easily accessible at any point. However, this is easier said than done, as implementing systems integration can typically cost $500K and take as much as 3-6 months, which can eat up a significant chunk of the research budget.
Collaboration and consolidation among front-end and back-end systems, as well as the emergence of advanced eClinical systems or modules, shows that the value of integrating will only continue to grow as users see the efficiency in storing and viewing their data on a single interface.
CDISC Standards Mandate Affecting U.S. and Japanese Submissions
Last December the FDA published a landmark package of Guidances, specifications and other documents governing electronic submissions. These have the force of law, which in effect made the use of CDISC standards mandatory in the United States and Japan by December, 2016 .
The FDA Guidances establish the framework for the requirement of standardized study data in submissions, and cover most aspects of submission data and documentation.
The new mandate increases pressure on CROs and sponsors to conform. In addition, the FDA is also considering updating the CDASH standards, which would also have a significant impact on current clinical trial processes.
Clinical Trial Paradigm Shift
A paradigm shift is taking place in the oncology clinical trial space, partially as a result of the Obama Administration launching its “Precision Medicine Initiative” in 2015. Precision medicine is an innovative approach that takes into account individual differences in people’s genes, environments, and lifestyles.
According to a White House release, a $215 million investment in the President’s 2016 Budget will be allocated to the Precision Medicine Initiative to pioneer this patient-powered research and provide clinicians with new tools, knowledge and therapies to select the treatments that work best for their patients .
The funding will be spread out between the National Institutes of Health (NIH), the Food and Drug Administration (FDA) and the Office of the National Coordinator for Health Information Technology (ONC) .
The objective for the National Cancer Institute is to accelerate the design and testing of tailored treatments for cancer by expanding genetically based clinical cancer trials. In June 2015, the NCI announced the launch of its nationwide clinical trial, utilizing DNA sequencing. In other words, subjects are grouped based on similarity in their genetic mutations, not the location of their cancer. The grouping is also known as “basket trials”. In the study, a few thousand patients at 2,400 sites throughout the United States will be sorted out into over a dozen treatments based on their tumor’s mutation .
The American Society of Clinical Oncology also recently announced the launch of a project that will provide patients with drugs targeting similar molecular abnormalities, and collect the data from their oncologists in order to monitor the effectiveness of the treatments.
The National Institutes of Health (NIH), in collaboration with other agencies and stakeholders, will launch a national, patient-powered research cohort of over a million Americans who volunteer to participate in research.
The trial subjects will be involved in the design of the Initiative and will have the opportunity to contribute various data—including medical records; profiles of the patient’s genes, metabolites (chemical makeup), and microorganisms in and on the body; environmental and lifestyle data; patient-generated information; and personal device and sensor data.
The Initiative will also include reviewing the current regulatory landscape to determine whether changes are needed to support the development of this new research and care model, including its critical privacy and participant protection framework. As part of this effort, the FDA will develop a new approach for evaluating Next Generation Sequencing technologies — tests that rapidly sequence large segments of a person’s DNA, or even their entire genome.
Although late to the game as compared to other industries, the clinical trial industry is now embracing information technology at a much greater pace. New and improved software applications and systems are being deployed at increasingly higher rates. Sponsors and CROs are adopting EDC, ePRO, CTMS, eTMF and other systems faster than ever, as the benefits have been proven to far exceed the expense and the FDA and other regulatory bodies are mandating electronic data submissions. Usage of these applications and systems will continue to improve the quality of data being collected, reduce the overall costs of clinical trials, and speed new drugs and products to patients.
By Glenn Keet, CEO at ClinCapture
And Eric Morrie, Director of Product Operations at ClinCapture
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