What Can Make Phase 4 Clinical Trials More Lucrative For Clinical Research Sites?
Here's how to make phase 4 clinical trials (either survey quality of life trials or standard-of-care trials). more lucrative for clinical research sites.
19 August 2015
The purpose of Phase 4 studies, which are clinical trials conducted on drugs or medical devices that have already obtained FDA approval, stems from the fact that pharmaceutical companies need to collect more data. This is for a number of different reasons such as obtaining additional safety data as mandated by the FDA, getting regulatory approval to make further advertising claims, removing black box warnings or any other such matters. Another primary purpose for conducting these post-approval or marketing studies is to get physicians, including their medical teams, accustomed to prescribing a particular medication as well as provide the pharmaceutical companies with valuable prescriber feedback. Finally, it gives the patients who qualify for these trials the option to try an FDA approved product at no cost to them as a sort of “trial period” which often lasts over one or, in some cases, two years.
Phase 4 studies are usually observed in one of two forms: Survey quality of life trials, or standard of care “real world” trials. I will explain each of these types of trials in this post.
More Phase 4 Clinical Trials
We are currently seeing a lot of these kind of studies right now in mid-2015 because pharmaceutical sponsors are getting ready for a busy 2016 — meaning they are doing a lot of feasibility assessments and protocol planning to prepare for this new onslaught of studies which will initiate next year. However, the research clinics still need studies to conduct now which is why, for the moment, there is a lot of pent up demand from the research clinics to want to take on any studies that they can get.
Savvy sponsors are taking advantage of the current supply and demand economics of the market and are rolling out phase 4 studies that they know many of the research clinics would never take on as soon as study supplies will increase. A lot of these sponsors see this relative quiet period as a time when they can complete their phase 4 trials while they are waiting for their pipelines to fill up with new products that they can conduct phase 1-3 studies on as a lot of the drugs for the traditional therapeutic indications have gone generic and the original hypotheses for how to more effectively treat many of these medical conditions have undergone paradigm shifts. Studies come in waves and phase 1-3 trials and phase 4 trials are usually inversely correlated to each other. Right now we are seeing a lot of phase 4 studies. I have been personally turning many of these because they are largely not lucrative for my research clinics. However, these trials might be worth doing for brand new investigators who need to get some experience in hopes of participating in future traditional trials. Sometimes established sites feel obligated to conduct these phase 4 trials because they want to establish a good working relationship with the sponsor. There are a few things pharmaceutical sponsors could do to perhaps, in my opinion, to make these trials a lot easier and therefore ultimately, more lucrative for the research sites.
Two Types of Phase 4 Studies
Let us first look at the two types of phase 4 studies that exist: survey studies and standard of care studies.
- Survey Studies: A survey, or quality of life study is exactly what it sounds like. Trial participants are recruited by the Investigators (usually from their own private practice) and are either given the approved medication that the participant is already taking, only now they will receive it for free, or trial participants are switched to the new medication from another medication that they were previously taking. Patients are then asked to fill out quality of life surveys which are usually paper-based. The research Site then needs to collect this data and upload it to an electronic case report form (eCRF) that the sponsor will later analyze. A site usually pays their participants around $50 per visit and the sponsor will pay the site or the investigator around $800 per patient visit when the study is completed. What sites typically do to maximize profits in these studies is enroll a high volume patients. Supervising the participant while they are completing their surveys, entering the data in the eCRF database, monitoring adverse events, and collecting other information such as demographics can be somewhat time consuming for the Sites — especially when many of these studies allow the study participants to remain in the studies for one year and sometimes even longer. A lot of adverse events could occur within this time period that the site would need to follow up on and document, not to mention changes in the concomitant medications that would need to be recorded. The problem only compounds itself if sites are using the high volume approach in terms of enrollment.
As you can see, the amount of work required and relative compensation received to conduct these types of trials, which on the surface seem relatively straightforward, is not on par with more traditional phase 1-3 trials in terms of both workload and commensurate compensation. What sponsors may want to consider in order to make these survey trials more lucrative for the research sites, is to eliminate the paper surveys and give each study participant a handheld electronic diary device which will remind the study participants when they would need to take their medication, fill out a survey, record an adverse event, and furthermore, have all of that data seamlessly uploaded to a virtual workspace such as Intralinks VIA®, and if possible, to an eCRF database as well. By removing the time consuming administrative tasks from the responsibility of the research sites, the sponsors would likely gain more (and better) data as the Sites would have a greater incentive to enroll more subjects since their reimbursements would be on a more commensurate level with the amount of work they would actually be doing. It would also allow the Investigators to focus their attention towards monitoring the safety of the trial participants rather than spending the majority of their time collecting surveys and transcribing information that the study participants could complete by themselves.
- Standard-of-care Studies: A more difficult type of phase 4 study is the standard-of-care (or real-world) study. In these cases typically a sponsor wants procedures of the study — such as investigational product dispensation, data collection, and safety — follow up visits to be done at the day program, hospital, out-patient clinics, or essentially anywhere except at the actual research clinic in order to obtain “real world” data and feedback from clinicians who typically do not conduct research. In these type of phase 4 trials, sponsors may not want the research staff to be too involved in the actual conduct of the study with the exception of funneling patients to these places and to supervising nurses who will be trained by the sponsors on how to do the various procedures.
One of my clinics just turned down a couple of these trials because the sponsor refused to allow any of the procedures to be done at the research site. While this may seem like an easy study for the site since very little is to be done by the research staff, if the clinicians in the “real world” fail to comply with the protocol, all of the responsibilities and “clean up” comes back to the site itself since they are tasked with entering all of the data into the eCRF database. It would be much more feasible for many sites to do these procedures onsite, but the sponsors want these studies done in real-world settings. What this translates to in a practical sense is that the research staff will have to remind, train, retrain and supervise the “real world” clinicians on something they are not very familiar with conducting a clinical trial.
Although you can get a high-volume of patients in these studies just like in the survey trials, the amount of pay may not always reflect the amount of work, namely supervising and following up with the real world clinicians, required in these studies.
One way that these studies could be more practical is to have some kind of virtual work space, again, like Intralinks VIA, where the Sponsor can train the clinicians in the real-world setting on how to use these tools and then upload the source documents to the virtual workstation themselves. The monitor can then have access to the virtual work stations and can be responsible for following up and training these staff members on conducting the protocol, with very minimal involvement from the site. The research site would, in theory, only serve as the regulatory center (of which the documents can also be stored on a virtual workspace), patient recruitment source, and supervisors of the virtual workspaces rather than the custodians of the paper-based records and data.
In my opinion, both survey studies and standard-of-care studies, can be made more lucrative and ultimately, more desirable for research clinics to conduct if sponsors can find a way to integrate virtual workspaces as the centerpiece and command center for the entire study. Taking away tedious tasks from the sites opens up opportunities such as better safety monitoring, higher recruitment levels, and instantaneous data that the sponsors can begin analyzing in real time rather than waiting for the sites to enter each data point manually on a paper source document first and eventually into the eCRF.
Dan Sfera is the CEO and President of The Clinical Trials Guru, LLC and DSCS Sweat Equity & Investments, LLC. Through these two companies Dan assists Sponsors and CRO's with Site Selection, Research Staff Training, Recruitment, Contract and Budget Negotiations and Business Development. Dan is also owner, partner and advisor for dozens of clinical research sites across the United States as well as Internationally. With a focus on marketing, finance and operations, he and his team have helped successfully launch many research organizations in the past 10 years.