Biomedical innovation is predicated, in part, on the willingness of human participants to participate in research investigations of promising compounds and technologies. Without controlled studies of how well new pharmaceutical agents, medical devices, and medical procedures actually affect the research participants who use them, it would not be possible to develop scientific bases for advancing medical care. Clinical investigation is fundamental to delineating the safety, effectiveness, and efficacy of new clinical approaches. However, clinical research does not proceed in a vacuum: It is subject to all manner of human vagaries that may affect participants’ capacity to participate. Just as a range of factors can hinder patients’ seeking and receiving healthcare services (Reif, Golin, & Smith, 2005
), barriers presumably have an impact on participants’ ability to participate in research, including their ability to adhere faithfully to research regimens. Ultimately, barriers, or even individuals’ perceptions or predictions of barriers, may affect the conduct and fidelity of clinical investigations.
The concept of “barriers” has played an important role in various theories about health behavior. It was originally introduced in Rosenstock’s (1966)
Health Belief Model in which barriers were construed as costs inherent in health action. In essence, the greater the perceived costs and the lower the perceived benefits to adhering to a protocol, the lower the likelihood a patient will adhere to it. In the Health Belief Model barriers were conceptualized as participative phenomena. A review of the model determined that barriers (e.g., inconvenience) were the most powerful determinant across various study designs and behaviors (Janz & Becker, 1984
). In contrast, Andersen’s (1968)
model of Health Service Utilization equated barriers with a lack of or reduced access to care. It broadened the Health Belief Model view of barriers to include those external to the individual and that were objectively identifiable (McCullock-Melnyk, 1988
). Despite the potential value of theory to undergird our understanding of barriers, much of the research that addresses the concept of barriers is not grounded on the Health Belief Model, the Health Service Utilization model, or any other theories. Instead, barriers research has been relatively atheoretical in nature, typically seeking simply to identify factors that predict specific behaviors (McCullock-Melnyk, 1988
A number of barriers that are related to seeking and receiving medical care have been identified. For example, researchers have grouped barriers to adherence to clinical regimens and self-care into categories related to: (a) the sequela of the particular disease state; (b) systems factors (e.g., access to clinics; length of appointments or procedures; gap between seeking and receiving care), and (c) patient factors (e.g., problems with medication, mental illness, incomplete understanding, and distrust of health care professionals (Spilker, 1991
; Robiner & Keel, 1997
). With regard to these factors, Cramer (1991a)
posits that forgetfulness is the most common personal factor undermining adherence to health regimens. The roles barriers play in the treatment of psychiatric disorders have also been studied (e.g., Bourgeois, 2005
). For example, financial barriers to the purchase of psychotherapy, psychotropic medication, or copayments for appointments, lack of transportation, and lack of child care have been identified as challenges to adherence in mental health care.
Methodologies for measuring adherence to health regimens in the literature have been heterogeneous. For example, some studies employ direct methods (e.g., observation of medication use, monitoring the level of medication use or metabolite in biological fluids, tracking clinical attendance). Others have used indirect methods such as patient report, pill counts, and electronic medication monitors (Rosen, Rigsby, Salahi, Ryan, & Cramer, 2004
). Generally, a combination of direct and indirect methods may be most effective in measuring adherence (Spilker, 1991
), though consensus on methodology remains elusive.
Quantification of adherence is central to evaluating adherence-enhancing strategies. Various approaches have been used to improve clinical adherence. These include increasing the flexibility of clinic scheduling; minimizing wait time for services; promoting frequent and positive contact between patients and health professionals; involving others (e.g., spouses) in patients’ care; providing information and education about disease management; simplifying regimens (e.g., streamlining dosing, reducing frequency of medication administration); and integrating contingencies to reinforce adherence (Cramer, 1991a
; Cramer 1991b
; Spilker, 1991
; Zinman, 1997
). Addressing patients’ personal circumstances and motivation also can be helpful (Cramer 1991a
). At times, mental health consultation can be beneficial, or even critical (e.g., when poor adherence becomes life-threatening [Kramer, Jacobson, Ryan, Murphy and the DCCT Research Group, 1994
]). In general, effective compliance-enhancing efforts are usually multifaceted (Bourgeois, 2005
). Identification of barriers may be a useful step toward developing and implementing strategies for overcoming them so as to facilitate consistency in how patients execute health behaviors.
Despite a robust literature addressing barriers to seeking and receiving healthcare for a broad range of conditions (e.g., Eggleston, Coker, Das, Cordray, & Luchok, 2007
; Krueger, Berger, & Felkey, 2005
; Rozanski, 2005
; Ward-Begnoche & Speaker, 2006
), relatively little attention has focused on barriers that affect participation in research trials and adherence to research regimens (Ross, Grant, Counsell, Gillespie, Russell, & Prescott, 1999
; Lowton, 2005
). Beyond those barriers inherent in clinical care that presumably are likely to generalize to the research context, barriers to participants’ enactment of research protocols may include variables associated with the conduct of research such as: the study demands including the experimental treatment regimens; understanding and accepting the necessity of randomization; perspectives of the research enterprise and funding agencies; and psychosocial factors. For example, barriers may be associated with experimental regimens (e.g., discomfort associated with procedures; frequency of appointments and procedures) as well as factors peripherally related to the study (e.g., financial, social support, child care, transportation, emotional functioning) or participants' personal resources (e.g., time, expenses). There is assumedly considerable variability in how any specific potential barrier may affect any individual participant. For example, whereas the primary hurdle for some participants may be transportation and parking at research sites, for others, the salient hurdles may be time (e.g., away from work, school, or family responsibilities), while for yet others the larger obstacles may be internal (e.g., motivational, organizational, mental health problems).
A fundamental challenge in conducting research is to enroll participants who are willing to volunteer and who can be counted on to comply faithfully with assigned experimental protocols. This process includes assuring that prospective participants understand the rationale for the study and the procedures that they would be expected to follow. In addition to the quantitative
challenges of study recruitment (i.e., enrollment of sufficient participants to satisfy sample size derived by power analyses) there are qualitative
challenges. The latter include selecting those participants who will be motivated and capable of consistently adhering to the research protocol. These have implications for all phases of a study, including recruitment, data collection, and data analysis. After participants’ randomization to treatment arms, the challenge is to promote consistent adherence to the protocol and monitor adherence so as to provide assurance that participants indeed did what they intended. Ethical prohibitions against coercing participants to comply with experimental regimens, even if they had earlier agreed to do so, necessitate that researchers develop positive approaches to facilitate regimen adherence (i.e., consistently fulfilling the experimental regimen) and follow-up adherence (fulfilling the research protocol’s planned assessments; See Kramer et al., 1994
; Robiner, 2005
Unfortunately, researchers have long observed that some study participants have difficulty fulfilling their intention of following regimens through endpoint (Collins, Williford, Weiss, Bingham, Klett, 1984
; Lasagna & Hutt, 1991
; Probstfield, Russell, Insull, & Yusuf, 1990
). Studies of diverse treatments and patient populations have revealed inconsistency in how well participants follow protocols. For example, participants may fail to take medications on schedule or may miss scheduled meetings with research staff. This is neither trivial nor inexpensive. A review of IRB records of 25,855 participants who consented to participate in U.S. industry-sponsored studies revealed that only 74% completed their trials (Gamache, 2002
). The potential role of barriers in contributing to such trends and costs by undermining adherence to clinical research is not known.
One way of conceptualizing research participation is that participants forego non-study related activities and navigate around potentially interfering circumstances to successfully follow investigational regimens. That is, participants may perceive, encounter, and need to surmount barriers so as to participate in accordance with study designs. Greater understanding of the role and magnitude of perceived barriers to research could yield clues to help participants, or research-eligible candidates, negotiate barriers so as to maximize participation in research and exposure to investigational regimens.
Despite the potentially important roles that barriers may play in research adherence, little is known about them or about how barriers may be affected by or interact with patient characteristics (e.g., age, gender). Similarly, it is not clear how transient or stable barriers may be over time (e.g., the course of a research trial) or how they may affect concurrent or serial trial participation. We are not aware of previous efforts to delineate how the salience of perceived barriers may change during the course of a study. Given that the long duration of some studies can affect adherence (e.g., Spilker, 1991
), it stands to reason that individuals' perceptions of barriers, as well as the circumstances and challenges that they contend with, may change over time. The aim of the present study was to examine the role and course of barriers to participating in a clinical trial. We explored patterns of barriers over the first four years of a 5-year study, as well as the effect of demographic factors (i.e., gender, age) on participants' perceptions of barriers.