Recruitment continues to be on the critical path for timely, on budget clinical trial completion. Despite the attention paid toward the tools that help stimulate enrolment including, educating patients regarding their condition, and ensuring that their participation is recognized at the end of the study, there has been only modest improvement in patient recruitment methods. While these are laudable initiatives, they are for the most part, directed to a certain demographic of clinical trial participants who are largely non-Hispanic, white, married, and middle-class. Being in the middle-class is associated with the following attributes: having money to manage, having health insurance, having a physician, being medically literate, and being interested in personal health1.
The importance of economic standing and levels of awareness in clinical trial participation was clearly demonstrated in an analysis of patients who were enrolled in National Cancer Institute trials over a one-year period. For every $1000 increase in mean income there was an increase of 0.7 patients, and for every 1 percent increase in the population with a college degree there was an increase of 1.51 patients2. These findings are in line with research conducted into how to get proportional representation of racial and ethnic groups in clinical trials. For example, the Hispanic population in the US is 16 percent but only 1 percent of clinical trial participants are Hispanic3. Although there are a number of cultural issues that influence this disparity, there is growing evidence that differences attributed to race/ethnicity may be more dependent on socioeconomic status4.
The primary focus of our recruitment incentive initiatives are targeting a subset of the population who are at the upper end of Maslow’s Hierarchy of Needs. They require self-fulfillment and acknowledgement of accomplishment and are, in sociological terms, defined as the middle and upper class. The 2005 population survey showed that this is 48 percent of the population. So, how can we appeal to the remaining 52 percent of the population, the ‘Forgotten Majority?’
There are a number of reasons why participation in a clinical trial for chronic conditions would be valuable to patients in the lower socioeconomic groups. The trial provides free healthcare, often including free medication unrelated to the drug under evaluation. Health insurance is not required. There is a free diagnostic panel which is much more extensive than would be conducted in a normal medical annual assessment. These attributes will also provide benefits to healthcare provider groups and payers, especially for long-term chronic conditions (e.g. diabetes, COPD, heart failure, depression, etc.). Many patients with these conditions use ER rooms (and other emergency clinics) as their primary source of medical care when acute episodes interfere with their normal daily lives. They do not seek chronic maintenance treatment as their primary concern about health is the maintenance of a normal lifestyle.
Many patients in the lower socioeconomic groups are less likely to be interested in their physical condition until it interferes with their day-to-day activities. The less well educated are not going to be interested in medical education and are not going to be influenced by appeals to the altruistic benefits of entering a clinical trial. Their primary concerns are based on short term survival, food, drink and lodging. There is another huge perceptual disincentive to consider participation in clinical trials. Popular media only ever report negative events in clinical trials or negative outcomes of drugs that have been approved for commercialization. Lastly, participation in a clinical trial is a drain on time without any obvious short-term benefits.
The most important aspect in engaging the ‘Forgotten Majority’ is how to find them. Medical databases are of no value and recruitment companies only have lists of those people who are interested in healthcare opportunities.
Those without health insurance or regular medical care have three primary sources of health management, emergency rooms, community clinics and local pharmacies. These are the locations that can be harnessed to make initial contact. Local pharmacies are particularly important. Pharmacy chains like CVS and Walgreens in the US provide swift accurate patient management but are not usually geared up to provide advice and help to chronic condition sufferers. Many of the ‘Forgotten Majority’ get medical advice from the independent pharmacies. They are more individual oriented as their success depends on satisfying the needs of the local community. They are in a position to identify those patients who cannot afford their maintenance medications and could, therefore benefit hugely from clinical trial participation. One other engagement opportunity is through social work departments. They are in close contact with the ‘Forgotten Majority’ and can identify patients who could benefit from participation in a clinical trial.
Identification of patients is of no value if there is no way of persuading them to consider participation. There is a bias against the concept of coercion as the prevailing thought is that the patient is putting him or herself at risk from the medication being tested or of getting placebo. Clearly the former risk is real but not significantly more than taking any approved medication. As clinical trials in chronic conditions are usually placebo controlled one argument against persuading patients to enter is that they may only receive the placebo. We believe that this is an industry misperception of the benefits that accrue from clinical trial participation. We all know about the placebo effect. It can be quite striking. One of the most common theories is that the placebo effect is due to a person's expectations. If a person expects a pill to do something, then it's possible that the body’s own chemistry can cause effects similar to what medication might have caused. However, an alternative explanation is that the frequency of visits to a physician can alter behavior. By continually reinforcing in the patient’s mind that they have a condition they modify their lifestyle to their benefit. Either way the patient is likely to benefit even if prescribed a placebo. Non-specific health benefits are considered to be more important than specific ones5. If this is accepted then clinical trials should be seen as a medical management tool that offers benefits irrespective of the test item prescribed.
The final hurdle is to identify how to make clinical trial participation attractive to a patient who is not particularly interested in their health. The main psychological component driving acceptance of giving time and effort to a process that has no obvious benefit is, “What’s in it for me?” If you are at the lower end of the socioeconomic hierarchy a financial incentive is probably the most compelling. We are not suggesting ‘bribery’ but developing a rational compensation rate based on fair market value for time, effort and inconvenience that can be applied across all clinical trials. Currently, this is highly variable and often woefully inadequate given the time and effort that patients are expected to put in to clinical trial participation.
In summary we ask you to consider that clinical trials, especially those in chronic conditions, constitute an undervalued medical management tool. Application of that tool will meet unmet medical need in a poorly served group of patients, “The Forgotten Majority.”
- Swanson GM, Ward AJ. J Natl Cancer Inst.1995 Dec 6;87(23):1747-59
- Sateren WB, et al (2002) How sociodemographics, presence of oncology specialists, and hospital cancer programs affect accrual to cancer treatment trials. J ClinOncol 20(8): 2109–2117
- "Dialogues on Diversifying Clinical Trials," sponsored by FDA’s Office of Women’ s Health and the Society for Women’s Health Research (2011)
- Du Xl et al (2008) Impact of treatment and socioeconomic status on racial disparities in survival among older women with breast cancer. Am J ClinOncol 31(2): 125–132
- Walach et al. The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – A secondary analysis. BMC Med Res Methodol. 2005; 5: 26