A guide to conducting late-phase research directly with patients
Late-phase research, once the exception, is becoming the rule for marketed pharmaceutical and medical device products. These studies, which are challenging to conduct (many involve thousands of patients over several years) are also expensive. According to a study published by the Tufts Center for the Study of Drug Development, the average cost of post-approval R&D is $312 million.[1]
Fortunately, some post-marketing evidence needs can be met with virtual studies (also referred to as direct-to-patient (DtP) and cyber studies), as opposed to traditional site-based studies. Even when it is not possible or advisable to eliminate sites from the equation entirely, their burden can often be dramatically reduced with the right approach to the protocol and some innovative thinking.
The challenges of relying on sites for post-marketing research
For many manufacturers, in addition to the cost of conducting late-phase research with a large number of sites, there are additional challenges that can impact study success:
- Competition for sites. Generally, given the number of studies underway, there is intense competition for sites willing to participate.
- The burden on sites. Many sites involved in late-phase studies are not professional research centers, but are rather front-line Health Care Providers (HCPs) focused on delivering the standard of care to their patients. Performing any functions beyond that is burdensome.
- The burden on patients. The more that patients are asked to do that is outside of their daily routine—and the longer they are expected to do it—the more likelihood that patients will either not comply or will drop out of the study.
- Geographic limitations. In site-based studies, patients typically need to be within a certain physical distance of the sites they must visit, limiting patient participation or increasing the number of sites required.
How virtual studies work
Fully virtual studies rely on patient outreach methods, such as digital recruitment, a remote consent tool e.g., eConsent and some form of data capture that does not require on-site visits to a physician’s office or hospital. (See details below.)
In this model, competition for sites and concerns over burdening them are irrelevant. Patients need not be in proximity to sites, and the data collection requirements fit more easily into their everyday routines, improving both compliance and retention. The impact on costs varies by the size and complexity of the study. The savings to be gained by moving to a virtual study for following 5,000 patients with an implanted medical device over 10 years would obviously be much more significant than in a study following seven patients with a rare disease for five years.
When it is not advisable to eliminate the role of a site completely, it is sometimes possible to develop a hybrid approach that keeps site involvement to a minimum—perhaps to perform a baseline screening, to confirm a diagnosis, or to consent the patient (in countries that do not accept informed eConsent).
Of course, ensuring patient care and effective study oversight are still primary priorities with a virtual study. In such a study, centralized investigator oversight and an effective medical monitoring and safety plan are still critical. It is also important that patients understand when to contact their primary care physician to manage their healthcare vs. the role of a Direct-to-Patient Contact Center which might be in place to support data collection and study logistics (e.g., remote visits, reimbursement, support with wearable devices). All of this requires an experienced research partner who understands how to work directly with patients and evolving technologies. It also necessitates having a deep understanding of the relevant regulatory environment and a commitment to effective study oversight and patient safety.
When does a virtual study make sense?
Determining whether—or to what extent—a research program can be accomplished with a virtual approach is a matter for discussion with a research partner experienced in virtual studies. However, there are certain established “givens.” A study might be a candidate for a virtual or hybrid virtual-site approach when:
The majority of patient assessments do not require on-site clinical work. Alternatives for data capture include platforms that support patient-reported outcomes (PROs), wearable devices or monitors in patients’ homes, sending an HCP (such as a nurse) to the patient’s home, or sending the patient to a lab (for example for a blood draw). Clearly, these methods will work in some therapeutic areas and not in others. For example, a virtual study will not work in an indication (such as cancer) that requires outcomes to be measured via CT scans.
Patients will be geographically dispersed. This could be due to a large number of required patients, which would traditionally necessitate a large number of sites. Or, it could be due to the fact that patients suffering from a rare disease are few and far between, requiring as much as a 1:1 ratio between patients and sites.
The study is to be conducted significantly in countries where regulations support remote patient management. For example, in the US, the FDA accepts eConsent as a valid patient consent method, while, at least for clinical development in the EU, this is currently not acceptable. Because informed consent regulations are constantly changing, the applicability must be assessed case by case.
Figure 1 illustrates the general type of decision points that would lead to a determination on the applicability of a virtual study design.
![Decision-tree-06 Decision-tree-06](https://icon.widen.net/content/s5wavtbhyt/original/Decision-tree-06.jpg?u=z8skf3)
The bottom line is that manufacturers should be open to the possibility of using a virtual approach for research and should consult with their virtual research specialist about it prior to finalizing the protocol. It may be that with a few minor alterations to a protocol, a study can be managed virtually, rather than via sites. It will be worth asking such questions as:
- Can that assessment be performed in the patient’s home?
- Do we really need that piece of data?
- Does it really need to be physician reported? What are the alternatives?
Virtual studies, where appropriate, offer advantages to manufacturers and patients. Taking a virtual approach may be valid in more cases than manufacturers realizing.
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Digital Disruption
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Clinical trial data anonymisation and data sharing
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Clinical Trial Tokenisation
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Closing the evidence gap: The value of digital health technologies in supporting drug reimbursement decisions
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Digital disruption in biopharma
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Disruptive Innovation
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Personalising Digital Health
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The triad of trust: Navigating real-world healthcare data integration
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Patient Centricity
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Agile Clinical Monitoring
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Capturing the voice of the patient in clinical trials
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Charting the Managed Access Program Landscape
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Developing Nurse-Centric Medical Communications
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Exploring the patient perspective from different angles
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Patient safety and pharmacovigilance
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A guide to safety data migrations
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Taking safety reporting to the next level with automation
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Outsourced Pharmacovigilance Affiliate Solution
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The evolution of the Pharmacovigilance System Master File: Benefits, challenges, and opportunities
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Sponsor and CRO pharmacovigilance and safety alliances
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Understanding the Periodic Benefit-Risk Evaluation Report
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A guide to safety data migrations
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Patient voice survey
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Patient Voice Survey - Decentralised and Hybrid Trials
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Reimagining Patient-Centricity with the Internet of Medical Things (IoMT)
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Using longitudinal qualitative research to capture the patient voice
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Agile Clinical Monitoring
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Regulatory Intelligence
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An innovative approach to rare disease clinical development
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Using innovative tools and lean writing processes to accelerate regulatory document writing
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Current overview of data sharing within clinical trial transparency
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Global Agency Meetings: A collaborative approach to drug development
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Keeping the end in mind: key considerations for creating plain language summaries
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Navigating orphan drug development from early phase to marketing authorisation
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Procedural and regulatory know-how for China biotechs in the EU
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RACE for Children Act
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Early engagement and regulatory considerations for biotech
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Regulatory Intelligence Newsletter
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Requirements & strategy considerations within clinical trial transparency
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Spotlight on regulatory reforms in China
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Transfer of marketing authorisation
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An innovative approach to rare disease clinical development
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Crossing the finish line: Why effective participation support strategy is critical to trial efficiency and success in rare diseases
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Diversity, equity and inclusion in rare disease clinical trials
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Identify and mitigate risks to rare disease clinical programmes
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Leveraging historical data for use in rare disease trials
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Natural history studies to improve drug development in rare diseases
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Patient Centricity in Orphan Drug Development
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The key to remarkable rare disease registries
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Advanced therapies for rare diseases
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Transforming Trials
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Accelerating biotech innovation from discovery to commercialisation
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Ensuring the validity of clinical outcomes assessment (COA) data: The value of rater training
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Linguistic validation of Clinical Outcomes Assessments
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Best practices to increase engagement with medical and scientific poster content
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Biopharma perspective: the promise of decentralised models and diversity in clinical trials
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Decentralised and Hybrid clinical trials
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Practical considerations in transitioning to hybrid or decentralised clinical trials
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Navigating the regulatory labyrinth of technology in decentralised clinical trials
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Biopharma perspective: the promise of decentralised models and diversity in clinical trials
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eCOA implementation
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Implications of COVID-19 on statistical design and analyses of clinical studies
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Improving pharma R&D efficiency
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Increasing Complexity and Declining ROI in Drug Development
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Innovation in Clinical Trial Methodologies
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Risk Based Quality Management
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Accelerating biotech innovation from discovery to commercialisation
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Cardiovascular Medical Devices
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COVID-19 navigating global market access
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Ensuring scientific rigor in external control arms
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Evidence Synthesis: A solution to sparse evidence, heterogeneous studies, and disconnected networks
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ICER’s impact on payer decision making
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Making Sense of the Biosimilars Market
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Medical communications in early phase product development
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Navigating the Challenges and Opportunities of Value Based Healthcare
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Payer Reliance on ICER and Perceptions on Value Based Pricing
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Payers Perspectives on Digital Therapeutics
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Precision Medicine
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Strategies for commercialising oncology treatments for young adults
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