The American Cancer Society estimates that there will be 240,890
new cases of prostate cancer (CaP) in the United States (US) in 2011
, and 33,720
men will die from this disease.
The initiation and progression of CaP may involve a complex array of both exogenous and endogenous factors.[2–5]
Although it is clear that clinical CaP incidence and mortality vary greatly between populations, the frequency of latent CaP is evenly distributed among populations, suggesting that external factors such as diet, physical activity and other lifestyle factors are important in the transformation from latent into more aggressive, clinical cancer.[2–5]
In addition, in most epithelial tissues, including the prostate, genetic progression and loss of cellular control functions are observed as the cell and tissue phenotype changes from normal to dysplasia (prostatic intraepithelial neoplasia or PIN), then to increasingly severe dysplasia (high grade PIN or HGPIN), superficial cancers and finally to invasive disease.
These features of prostate cancer, namely, high prevalence, long latency, significant mortality and morbidity, and the availability of intermediate predictive stages of progression, provide the most promise for evaluating agents for chemoprevention. Chemoprevention is the prevention of induction and inhibition of the development of preinvasive and invasive cancer and its progression or treatment of identifiable pre-cancers.
Several nutrients and nutrient derived agents have continued to demonstrate promise as potential chemopreventive agents in epidemiological, laboratory studies and pilot or early phase I–II studies. In spite of the unique opportunity for prevention as well as unavailability of alternative treatment strategies for this high risk group of men other than surveillance, chemoprevention trials for prostate cancer prevention have not been successful.
Recruiting participants who are at high risk for cancer continues to be costly and presents unique challenges globally.[6–7]
The ability of research teams and institutions to recruit eligible subjects at high risk for cancer, who are willing to
adhere to the study protocol in randomized clinical trials is an essential component of translational research
that may impact generalizability of reported results.
Several barriers and facilitators to recruitment in chemoprevention trials have been documented. These include subject, protocol and infrastructure related factors. With respect to subject-related factors, chemoprevention trials are targeted at high risk, healthy individuals who do not have any signs and symptoms of the disease
who are often unwilling to be randomized to placebo-control arms of the trial, especially if the trial involves immense burden to them, including compliance to agent and diet, frequent visits, completion of monitoring tools and most importantly if these studies include invasive procedures for biomarker evaluation such as biopsy, fine needle aspirations or bronchoscopy.
In addition, most of the agents under study are available in similar doses as over the counter (OTC) supplements or in “natural” forms that subjects have access to. This increased availability has encouraged subjects to opt out of participation in randomized clinical trials, where there is a chance of being assigned to a placebo arm.[9–10]
Protocol-related factors include unrealistic exclusion and inclusion criteria such as use of other nutrient supplements and concomitant medications used for cardiac prophylaxis such as Aspirin or lipid lowering regimens, especially if these studies are targeted to otherwise healthy individuals. Institutional or infrastructure-related barriers include unavailability of culturally competent teams[7,9]
with investigators not communicating with the community and target population who are stakeholders as well as
location and accessibility to research sites noted. While important for the protection of the privacy of human subjects, challenges have also
emerged related to the use of
community members and peers in subject recruitment as concerns related to the
privacy of health information have been raised
Supportive marketing and public relations departments at sites that use community radio, newspaper and other published media advertisements, direct and indirect mailings, internet postings, development and distribution of decision aids
and print media exposure of clinical trials
utilizing culturally and literacy competent and experienced teams
have demonstrated success in attaining target recruitment numbers in other cancer prevention trials. The efforts of experienced and committed physician's investigators
who are key stakeholders have also been shown to be vital to the success of clinical trial recruitment. Research teams that pay meticulous attention to patient recruitment, retention, individualization of procedures with respect to multi-institutional sites
and frequent monitoring of subject screening, recruitment and randomization logs to inform revisions to procedures have been shown to significantly improve recruitment in clinical trials. In spite of the available literature on effective recruitment strategies, to date, few reports have identified the unique challenges and potential solutions to recruitment in chemoprevention trials using nutrient-derived agents for cancer prevention in otherwise healthy, high risk populations.
We are currently recruiting men diagnosed with High Grade Prostatic Intraepithelial Neoplasia (HGPIN) or Atypical Small Acinar Proliferation (ASAP) in a multi-center, phase II randomized, placebo-controlled chemoprevention trial of Polyphenon E to prevent progression to prostate cancer. As with most chemoprevention trials, we have experienced several challenges with accrual. Identification of challenges and solutions to recruitment barriers in chemoprevention trials may guide researchers in the future design of contemporary chemoprevention trials and additionally, to better select, focus and invest in strategies that are the most productive and efficient to recruit high risk populations. The goal of this paper is to describe the strategies, successes, challenges and potential solutions towards achieving target recruitment accrual in future chemoprevention trials.