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.
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.
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.