Patient Recruitment: Clinical Research's "White Whale"?

Past blogs have discussed the rapid growth of the CRO industry, which many analysts have pegged at around $30B (excluding preclinical CROs). With an estimated 800-1,000 CROs on the planet, there is no lack of companies available to run a clinical trial. Much like humans need food to survive, clinical trials need patients to exist (I almost used the analogy of gas to a car and realized Elon Musk made that thinking obsolete). Ironically, in an industry where one of the end results is improved patient care, patients for clinical trials are hard to come by.

The Issue

Sample headlines from a google search related to "clinical trial patient recruitment challenges" include:

• "Fear and Mistrust Keeps Patients from Trials" - Clinical Leader, 12/2/16

• "JDRF Hopes Technology will Solve Patient Recruitment Challenge" - Clinical Leader, 8/30/16

• "Tackling Patient Recruitment Challenges in Clinical Trials" - OncLive, 3/26/14

• "Patient Recruitment for Clinical Trials: Something to Chew On" - Multiple Sclerosis News Today, 7/13/16

The number of articles, blogs and commentary on he challenges with patient recruitment seems infinite. The stats presented really put the issue into perspective:

• Only 3% of adult cancer patients participate in clinical trials

• One analysis showed that 40% of oncology trials failed to achieve patient recruitment while more than 3 out of 5 Phase III trials failed to do so

• New data shows that only 40 percent of Americans have a positive overall impression of clinical trials

• Only 35 percent of Americans indicated that they were “likely” to enroll in a clinical trial

• Applied Clinical Trials reported that nearly one-third of sites performing clinical trials never enroll a single patient

• Another report stated that nearly 80% of clinical trials fail to meet their enrollment timelines and up to 50% of research sites enroll one or no patients

• Covance reported that almost $2B was spent between 2006-2010 on underperforming sites

• Up to 85% of clinical trials are delayed due to enrollment

Reasons Why Patient Recruitment is a Challenge

More Trials

Rapid growth in clinical trials has created more trials competing for the same patients. Per ClinicalTrials.gov, the number of trials registered on the site has increased from 101,150 in 2010 to 231,860 in 2015 - which is a 15% compound growth rate. Clearly these are not all active trials but that means there could be as many as 130,000 new trials since 2010. 2016 alone had almost 25,000 new trials registered.

Complex Protocols

Applied Clinical Trials has a great chart that shows the relationship between more advanced protocols and patient recruitment. As you can see from the chart below the average % of enrolled patients to screened patients dropped from 70%+ in 2007 to closer to 60% in 2011. Protocols have only gotten more complex in recent years. Complex protocols can result in a more specific and stringent selection of patients adversely impacting patient recruitment.—subject screening and enrollment at sites, besides increasing the associated site burden.

Patient Awareness

Having spent a large portion of my career in the clinical research industry, I take for granted my knowledge of clinical trials. The reality is the general public is uninformed. The data shows that awareness is lower in minorities as well.

• CISCRP research has found that fewer than one in 20 Americans know where to find information about relevant clinical trials

• One National Institutes of Health study of more than 1,000 US adults found that only one in three had even heard of clinical trials

• Black Americans comprise 13.2% of the population but just 5% of clinical trial participants

• Hispanics are 16% of the population, but only 1% of trial participants

• 67% of Americans are white but represent 83% of clinical trial participants

I guess it shouldn't be a surprise that enrollments are low if most patients aren't aware clinical trials may be an option.

Inexperienced Sites

A high percentage of sites that add clinical research as a supplement to their business fail. Clinical research requires additional support staff, equipment, an ability to mine patient data, technology and a strong understanding of the time and costs associated with participating in a clinical trial. Emissary.com reports that about half of clinicians involved in research in any given year don't participate a year later. Another study shows that one-third of sites performing clinical trials never enroll a patient. Just because someone is a physician it doesn't mean they have the experience to effectively manage a clinical research business.

Patient Trust

The Center for Information and Study On Clinical Research Participation has a great report on public perceptions of clinical trials. I can't post all the data (although I recommend reviewing the report) but here are highlights I found interesting:

• The willingness of those interviewed to participate in a clinical trial dropped from 50% in 2013 to 38% in 2015

• A higher proportion of respondents in 2015 (35%) agree that research participants are gambling with their health compared to 2013 (29%) – however, this proportion is still lower than the percentage seen in the 2005 survey (49%)

• The possibility of side effects remains the top perceived risk (43%)

• Pharmaceutical web sites and clinical trial advertisements are the least trusted sources of information

Clearly, patients have the most trust in their physicians. A Research America poll found that 80% of 1,000 respondents claim a physician’s recommendation is an important factor in deciding to participate, yet only 22% of patients said a health care professional has talked to them about it. Physicians are expected to provide advice that's best for their patient's overall health. Patients will think long and hard about enrolling if their physician feels it could have a positive outcome.

There are numerous other issues ranging from patient logistics (i.e. access to transportation to participate in a trial) to physicians being concerning with losing patients if they refer them to another practice conducting a trial. Participating in a clinical trial is a personal choice. Having the right information to make a thoughtful decision is key to trial enrollment. Physicians are the most trusted source for that information - patients greatly value their recommendations.

The Cost

While there aren't solid industry statistics that break down the total industry cost of recruiting patients, I tried to piece together some data to demonstrate the potential magnitude of the costs. Here goes:

Per Phrma.org, 2013 below is a chart of estimated 2013 U.S. active clinical trials and clinical trial participants (which should represent 40-45% of all 2016 global active recruiting studies per clinicaltrials.gov).

Per the data in 2013, there were 6,199 trials active in the U.S. with 1,148,340 patients enrolled. Let;s figure out how many patients need to be identified to enroll 1,148,340 patients using Forte Research Systems' average recruitment metrics:

• 69% of patients will fail the pre-screening process

• 58% of patients will decline to participate in the clinical trial

• 32% of patients will fail the screening process

• 18% of patients will drop out of the trial

Here is the calculation:

By working backwards, I was able to determine that 15,817,460 patients needed to be identified/pre-screened to enroll the 1,148,340 patients. Now to figure out the potential costs of pre-screening and screening patients. I am going to make a few assumptions:

• Pre-screening a patient costs roughly $200 per patient. This includes reviewing medical records, making calls to patients, etc... SOCRA.org has an estimate of $240 per patient from previous experience that I'll use as a sanity check.

• Screening a patient costs roughly $1,500. A lot more variability here, really depends on the indication, and I've seen screening costs as high as $2,000. I'm going with the assumptions that screening costs can be between 1,000-$2,000, so I'm taking the average.

Here are the results:

Using our rough assumptions, it would have cost a staggering $6.252B to recruit all the patients active in U.S. clinical trials in 2013. Keep in mind this isn't an annual cost as many of these trials could have recruited patients prior to 2013, they just happen to still be active. Still, this demonstrates the significant cost of patient recruitment. Let's take a look at the "unproductive" costs or the costs associated with pre-screening and screening patients that aren't enrolled or drop out of the trial.

"Unproductive" costs are $4.118B or 66% ($4.118B/$6.252B) of our total cost. To put in perspective, more money is spent on patients that aren't enrolled than on those that are. Many companies have entered the market trying to reap the financial rewards from solving this issue.

Other costs include:

• The amount spent on activating unproductive clinical trial sites. I've seen this estimate range from $10,000 to $50,000 per site

• The cost of not meeting study timelines. Every month delay is another month a CRO needs to get paid to manage the trial, time spent on a new trial is spent on a delayed one, etc...

• Loss of revenue from time that a successful product could reach the market

• Lastly, it could mean that a biotech runs out of cash and can't even finish the trial

Solutions???

A variety of companies are attempting to solve (at least improve) the patient recruitment challenge. A google search brings up an infinite list of companies. It is clear that technology will play a greater role in patient recruitment. Here is a sample of the companies that came up in my search:

• CSSi - Recruiting Patients - Driving Enrollment - Across the Globe

• BBK Worldwide

• DAC Patient Recruitment Services

• Clariness

• Elligo Health Research (I am aware of Elligo as I used to work with the founders of this business)

• Trialbee

Currently, there isn't a big name that is dominating the market. Acurian is probably the most well known and they were acquired by PPD (shows the CROs know the importance of patient recruitment). Typical for the clinical research industry, it will be interesting to see which companies become the true leaders in this space. More than likely, several of them will merge and provide a suite of services designed to address the multiple issues adversely impacting patient recruitment.

Wrap Up

Patient centricity is now a widely used phrase in the industry. “Patient centricity” has been defined as the process of designing a service or solution around the patient. The companies that best marry patient centricity with technology will likely be the top players in this space. The objective of clinical research is to discover and develop new medicines and therapies improve patient health. Profits, rising share prices and market share are all byproducts of focusing on the patient. Patients are the customers and all of us who work in the industry would be wise to listen to their needs when it comes to participating in clinical trials - the future of the industry may depend upon it.

Jason Monteleone is President at Pivotal Financial Consulting, LLC. A Strategic Financial Consulting Firm serving the Clinical Research Industry. Jason can be reached at jmpivotalfinancial@gmail.com. Follow me on Twitter @JMPivotal.