Examination of Clinical Trial Costs and Barriers for Drug Development. 4.3 Difficulties in Recruiting and Retaining Participants

07/25/2014

In interviews, expert consultants and representatives from pharmaceutical and biotechnology companies and CROs cited patient recruitment as one of the most significant barriers to conducting clinical trials in the United States. Failure to recruit sufficient numbers of patients can result in costly delays or even cancellation of the entire trial (Weisfeld, English, & Claiborne, 2011).

Patient recruitment difficulties are caused by a number of factors, some of which are fairly universal across clinical trials, while others arise due to characteristics of a particular disease or trial. One obvious factor is study size; as discussed previously, trends toward comparative and chronic disease studies contribute to a need for larger numbers of participants. Another common problem is finding willing individuals to participate in clinical trials. Most company representatives also expressed frustration over competition among drug companies for the same patient pools, explaining that multiple large companies often find themselves targeting the same big markets at the same time. For example, many sponsors are interested in pursuing anti-inflammatory drugs because the road to regulatory approval is clear and well-established for these drugs. These companies then compete to enroll patients with a few specific diseases (e.g., asthma, multiple sclerosis, and chronic obstructive pulmonary disease) on which they would like to test their drug. On the other hand, for smaller markets, recruitment might be hindered by the simple fact that patients are few and far between. Many smaller companies focus on developing drugs for orphan diseases, for which the potential pool of patients is, by definition, limited.

There are several factors specific to certain disease areas or trial types that can make it especially difficult to recruit and retain patients in sufficient numbers. For some diseases (such as certain cancers), problems of access arise because patients are located mostly in remote areas, far from the clinical trial sites that are selected based on where investigators are (English, Lebovitz, & Giffin, 2010). Patient retention is a common problem in studies involving long-term endpoints (e.g., multiple sclerosis), lengthier treatments, or negative side effects that cause patients to become fatigued or sick and drop out. Additionally, some trials have narrow patient eligibility criteria that intentionally disqualify many potential participants who have the targeted disease but do not meet other inclusion criteria (English, Lebovitz, & Giffin, 2010). The goal in excluding these patients is to conduct a pure experiment that is free from the confounding influences of comorbid illnesses, concomitant medications, and other such factors (Kramer, Smith, & Califf, 2012). Enrollment restrictions such as these may simplify the trial itself but make recruitment more difficult.

Even if there were an abundance of readily available, ideally suited patients, participation in clinical trials would still be greatly hindered by public attitudes, incentives, and lack of knowledge. Both physicians and their patients are often unaware of clinical trial options, and often times it is only patients of higher socioeconomic status who have the resources, knowledge, and motivation to seek information about a disease, including clinical trials (English, Lebovitz, & Giffin, 2010). Furthermore, physicians may not be able to determine whether standard treatment or a trial is the better option for their patients. To some extent, these problems arise from the separation between the realms of scientific research and clinical care in the United States and the lack of engagement among physicians in the clinical research process (discussed in greater detail in Section 4.7) (Bonham, Califf, Gallin, & Lauer, 2011).

For their part, patients who are aware of clinical trial options might be hesitant to participate for a number of reasons. Fear is a major deterrent; patients understand that taking part in clinical research is good for public health but feel uncertain as to whether it is the best option for their own personal health. Many people are ill-at-ease with the idea of serving as “guinea pigs” and possibly suffering unexpected side effects, while others might assume the new drug is likely to be effective and worry instead about being assigned to a no-treatment or placebo group (Mills, et al., 2006; Welton, Vickers, Cooper, Meade, & Marteau, 1999). A related issue is discomfort with randomization and the idea that choice of treatment will be based on chance rather than the decision of a doctor or the patients themselves (Jenkins & Fallowfield, 2000). Media attention to cases with negative outcomes (e.g., serious side effects or deaths) has also fostered distrust of industry-sponsored trials, and many patients believe that industry will put its own interests ahead of theirs (Weisfeld, English, & Claiborne, 2011; English, Lebovitz, & Giffin, 2010). Awareness of deceptive, exploitative, and racist past practices in experiments, such as the Tuskegee syphilis study, continues to fuel this distrust, particularly among some minorities and cultures within the United States (Weisfeld, English, & Claiborne, 2011; Shavers, Lynch, & Burmeister, 2000).

Aside from the uncertainties involved, participating in clinical research may simply be inconvenient or overly burdensome to patients. By signing up for a trial, patients might subject themselves to interruptions in care, physical and emotional stress caused by leaving their regular provider, time and travel costs, (including transportation to the study site and lost income), and large volumes of confusing paperwork associated with the informed consent process (English, Lebovitz, & Giffin, 2010). Finally, language and literacy barriers may also deter some from participating (Weisfeld, English, & Claiborne, 2011).

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