Drivers of Patient Interest in Clinical Trial Referral

Summary
Patient recruitment remains a major determinant of clinical trial costs and timelines. Outside of lack of awareness of clinical trials, research conducted by MediGuard.org–an online service monitoring medication safety for 2.5 million patients–found that condition, side effects, treatment satisfaction, previous clinical trial experience, and country of origin are all significantly related to patient interest in study referral. However, age, treatment satisfaction and condition are the best predictors of interest. These findings were based on the analysis of 206 patient feasibility and recruitment screening studies conducted with 8,599 MediGuard members from January 2009 to July 2011 in the US or UK.

In order to expedite study timelines and decrease costs, researchers are actively seeking opportunities to speed enrollment, and supplemental patient recruitment is one such option. We define supplemental patient recruitment as the practice of pre-qualifying community-based patients and referring them to clinical trial sites for study screening.

The portion of patients available for supplemental recruitment is large, with studies suggesting that fewer than five percent of all eligible adult patients are enrolled in therapeutic studies and this proportion is even lower among the elderly, women, and racial and ethnic minorities.¹ To better understand reasons why these patients do not participate in clinical trials, ECRI conducted a meta-analysis of 14 published studies and concluded that the following three factors were important:

• Fear of placebo or randomization

• Too far to travel

• Desire to have the physician choose the treatment rather than accept a process that uses randomization to assign patients to a treatment group.²

Primary research conducted by MediGuard.org and published in the 2009 Industry Standard Research report titled Success in Patient and Investigator Recruitment, however, showed different results. The MediGuard survey of clinical trial naïve patients found that the primary reason that patients do not participate in clinical trials is simply that they are unaware of opportunities to do so (69 percent of respondents).3 As a result, physician investigator sites and other researchers are actively seeking opportunities to make community-based patients aware of clinical trials. With ever-increasing numbers of patients seeking health information on the Internet, digital outreach programs through search engines, social media, and on-line patient communities are becoming more commonplace. Although the number of clinical trials using supplemental patient recruitment has grown substantially, there is little information available in the literature on patient level of interest in studies and patient characteristics associated with study interest.

To that end, we searched across all feasibility and recruitment screening studies conducted with patients between January 2009 and July 2011 in the United States or United Kingdom by MediGuard.org. Specifically, we identified patient questionnaires that contained a patient consent to contact if a clinical trial were available at a nearby site. The response to this question on consent to referral (yes, no) was extracted into a patient-level, de-identified study database, along with any other patient characteristics available from the screening survey including: treatment history (disease, number of medications, side effects, treatment satisfaction), patient demographics (age, gender, race, country, previous clinical trial experience), and other socioeconomic variables (employment, insurance status). 

All surveys were conducted online with members of MediGuard.org, a free online service that monitors the safety of prescription medicines, over-the-counter medicines, and healthcare supplements for over 2.5 million patients in the United States, United Kingdom, France, Germany, Spain, and Australia, which was initially funded by Quintiles. Patients enrolling in the MediGuard.org service consent to be contacted about research opportunities as part of the registration process and double-consent to participate in any individual research study following receipt of an e-mail invitation to participate.  

We extracted information from 206 feasibility and recruitment screening studies involving 8,599 patient responses. Of those respondents, 68 percent were aged under 65 and 68 percent were female. Only 14 percent of respondents did not have health insurance, although a majority (55 percent) was unemployed (i.e., unemployed, working in the home, retired, or disabled). 

Across all conditions, the average rate of patient interest in being referred for a clinical trial was 72 percent.  Patient interest ranged from a low of 56 percent among cancer patients to a high of 83 percent for those with chronic infectious diseases (e.g., HIV, hepatitis). 

Drivers of patient interest
Based on univariate regression where characteristics are grouped based on relationship with interest in referral, disease condition and previous clinical trial experience both had a significantly positive effect on patient interest in study referral. Two additional variables were also significantly related to interest: presence of bothersome side effects (the more bothersome the side effects, the greater the interest) and satisfaction with current treatment (the lower the treatment satisfaction, the greater the study interest). Patient age, gender, race, number of medications, employment status and insurance status were not significantly related to a patient’s interest in study referral. 

The results of the step-wise regression, however, show that the three variables that best explain patient interest in studies include:

• Age

• Condition

• Treatment satisfaction

Specifically, we found that patients age 65 and over are less interested in participating in a clinical trial than those who are under age 40. Additionally, patients who are dissatisfied with their medications are significantly more interested in studies. Finally, with respect to disease, in thinking of cardiovascular disease/diabetes as a reference condition, we find that patients with cancer and gastrointestinal conditions are significantly less interested in studies as compared to the reference of cardiovascular disease/diabetes.

Due to the lack of existing literature examining patient interest in clinical trial referral across conditions, it is difficult to compare our findings with previous studies. One possible explanation for the variance in interest between CV/metabolic disease and cancer or gastrointestinal conditions is the patient’s relationship with their managing physician. This relationship manifests itself in two different ways. In the case of cancer, for example, feedback from qualitative discussions with patients and responses to other quantitative survey questions suggests the cancer patients have such a close relationship with their physician that the patient’s lack of interest in referral may be driven by their desire to remain under the care of their personal oncologist until the time that their managing physician recommends a clinical trial. 

Unlike cancer patients, data on-hand from MediGuard.org patient surveys suggests that gastrointestinal patients do not place a high level of importance on their physician’s recommendation for (benefit of participation) or against (drawback of participation) a potential clinical trial. In fact, many of our patients screened for heartburn/GERD studies are self-treating with OTC medicines and are not in close contact with their primary care physician about their current symptoms or treatments. As a result, we believe that the low interest in clinical trial referral amongst these gastrointestinal patients stems from an overall low level of engagement with their underlying condition. 

Our data should be viewed within the context of some limitations. First, we studied interest in referral based on responses to screening questionnaires, not through actual clinical trial enrollment.

These study results also are generated from the opinion of community-based patients being offered the opportunity for referral to a different physician for a clinical trial. Thus, the findings could differ from studies examining feedback from patients screened within a physician’s own practice.

Another limitation of this analysis is that it is difficult to control for protocol-specific factors that could influence a patient’s desire to participate in a study. Protocol-driven elements such as the study time commitment (e.g., study duration, number of visits, frequency of visits), burdensome study procedures (e.g., lumbar punctures), or medication washout/switching are frequently mentioned by patients in MediGuard.org surveys as drawbacks of participating in a clinical trial. The current study was unable to control for these factors.

Finally, it is possible that the unique characteristics of the MediGuard.org patient population account for its high interest in clinical studies. As of September 2011, MediGuard.org had over 2.5 million members and is much larger than other online health-oriented social networks.⁴ While this may limit generalization of findings to non-digital patients, recent statistics from the Pew Foundation suggest that nearly 60 percent of all US adults are actively seeking health information on-line (75 percent have internet access and 80 percent of those search for information on their condition or medicines).⁵  As the population ages and Internet-enabling technology continues to evolve (e.g., smart phones, iPads), remaining concerns around the generalizability of digital patients should continue to diminish.

*Editors Note: The full peer-reviewed version of this article will appear in an upcoming issue of Applied Clinical Trials.

References

1. http://www.mssm.edu/about-us/news-and-events/iom-and-mount-sinai-collaborate-to-examine-issue-of-declining-participation-in-clinical-trials
2. http://www.pfizer.com/files/research/AAHP_CT_Guide.pdf
3. http://www.news-medical.net/news/20091005/Challenges-in-patient-recruitment-for-clinical-studies.aspx
4. Cascade E, Stephenson H, Bharmal M, Cabell CH, "Direct-to-Patient Enrollment Strategies," Applied Clinical Trials, September 2010, pp 44-50.
5. Pew Research Center’s Internet & American Life Project: The Social Life of Health Information, 2011. May 12, 2011.

Elisa Cascade is Vice President, MediGuard.org, Quintiles (1801 Rockville Pike, Suite 300, Rockville, MD  20852. Office: +1 301 272 3223; Mobile: +1 703 597 6642; Fax: +1 301 272 3299; e-mail:elisa.cascade@MediGuard.org) and Andrew Burgess is Statistical Scientist, Late Phase Biostatistics, Quintiles, Reading, UK; and Mark Nixon, Associate Director, Late Phase Biostatistics, Quintiles, Reading,  UK.