Impact of a Clinical Trial Initiative on Clinical Trial Enrollment in a Multidisciplinary Prostate Cancer Clinic

Abstract

Purpose

Clinical oncology trials are hampered by low accrual rates with less than 5% of adult cancer patients treated on study. We evaluated clinical trial enrollment in our Multidisciplinary Prostate Cancer Clinic (MPCC) to assess if a clinical trial initiative, introduced in 2006, impacted enrollment.

Methods

The trial initiative included posting trial specific information in clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with trial specific educational information. We evaluated frequency of clinical trial enrollment for men with newly-diagnosed prostate cancer seen in the MPCC from 2004 to 2008. Logistic regression evaluated the impact of patient characteristics and the clinical trial initiative on trial enrollment.

Results

The median age of the 1,370 men was 64 years. 32% had low-risk, 49% had intermediate-risk and 19% had high-risk disease. Overall, 74% enrolled in at least one trial and 29% enrolled in more than one trial. Trial enrollment increased from 39% before the initiative (127/326) to 84% (880/1044) after the trial initiative. Patient enrollment increased in laboratory studies (25% to 80%), quality-of-life studies (10% to 26%) and studies evaluating investigational treatments and systemic agents (6% to 15%) after the trial initiative. In multivariate analysis, younger men (p<0.001) and men seen after implementation of the clinical trial initiative (p<0.001) were more likely to enroll in trials.

Conclusion

Clinical trial enrollment in our Multidisciplinary Prostate Cancer Clinic was substantially higher than seen nationally in adult cancer patients and enrollment rates increased after introduction of a clinical trial initiative.

Introduction

One in six men in the United States will be diagnosed with prostate cancer in their lifetime.¹ Although progress has been made there is still much to be done to improve the diagnosis, treatment, survival and quality of life for this patient population. Prostate cancer remains the second leading cancer cause of death among men in the United States and prostate cancer survivors frequently experience long-term side effects of treatment.^2,3 An obstacle to research progress is arguably the low rate of clinical trial enrollment. Recent reports estimate only 2 to 5 % of adults diagnosed with cancer are participants in clinical trials although up to 20% of adults may be eligible for disease specific clinical trial participation.^4-6

One barrier to clinical trial enrollment is lack of awareness of available clinical trials. A survey of nearly 6,000 cancer patients found 85% of cancer patients were either unaware or unsure that participation in clinical trials was an option although 75% of these patients indicated a willingness to consider enrolling in a trial had they known it was an option.¹³ Lack of physician awareness of clinical trials and lack of physician time to discuss clinical trials also contribute to limited patient awareness of available clinical trials and subsequent low clinical trial enrollment.⁵

A clinical trial initiative was introduced into our center's multidisciplinary prostate cancer clinic as a possible means to increase clinical trial enrollment and overcome these barriers. The initiative was based on the premise that providing an organized, methodical approach to incorporating clinical trial recommendations into an established clinic could facilitate greater patient understanding and consideration of clinical trial options. In this manuscript we report the impact of our clinical trial initiative on trial enrollment at a comprehensive cancer center.

Methods

A multidisciplinary prostate cancer clinic (MPCC) opened in 2004 in the Genitourinary Center at the University of Texas MD Anderson Cancer Center. The clinic provides detailed education to newly diagnosed patients about their disease and appropriate treatment options. All patients meet with a urologist and a radiation oncologist. A medical oncologist consultation is available for patients recommended for either systemic therapy or active surveillance. At the end of the clinic visit, patients receive both verbal and written detailed recommendations for treatment options.

A clinical trial initiative was introduced in the MPCC in 2006. This initiative focused on informing patients of their clinical trial options and streamlining the referral process to educate patients on appropriate clinical protocols. Information about specific protocols and eligibility criteria were posted in the clinic area for physician reference. Trial options were discussed at the time of each specialists' consultation. The visit was facilitated by a clinic-specific advanced practice nurse and each patient received a patient-specific summary letter of treatment recommendations that included a list of “Recommended Clinical Trials” (example shown in Figure 1). The summary letter was reviewed with each patient by the clinic advanced practice nurse at the completion of their visit. Patients indicating interest in a clinical trial received either a same-day consultation with the research team or additional trial-specific print information.

Figure 1. Summary letter provided to patients at the completion of the multidisciplinary prostate cancer clinic.

We evaluated 1,370 men with non-metastatic, localized prostate cancer seen in the MPCC from 2004 to 2008 and subsequently treated at MD Anderson Cancer Center to determine if the clinical trial initiative increased clinical trial enrollment. This date range was selected because it included men two years prior to and two years after the initiation of the trial initiative. The number of patients seen in the MPCC is larger after the start of the trial initiative because more appointment slots were available to patients in the later years. Each patient evaluated in the MPCC was self or physician referred, recently diagnosed (within 6 months) with localized disease, and had not yet received definitive treatment. The primary outcome was enrollment in a prostate cancer clinical trial. The prostate cancer clinical trials were divided into four categories: a) laboratory studies, b) quality of life (QOL) studies, c) procedure studies, and d) novel studies (Table 1). Two physicians (KEH, DAK) and a Clinical Nurse Specialist (LM) categorized the trials. All three agreed on the final characterization for all trials. The clinical trials that each patient enrolled in were obtained from the electronic medical record.

Table 1. Clinical Trial Categories.

Category	Trials
Laboratory	Blood draws and tissue banking trials
Quality of Life	Questionnaire and survey studies
Procedure	Trials evaluating new radiation and surgical techniques
Novel	Trials evaluating investigational treatments and systemic agents

The covariates evaluated for association with enrollment in a prostate cancer clinical trial included: age, self-reported race, residence, prostate cancer risk group and year of visit. Age was evaluated as a continuous variable. Age was also dichotomized at the median (64.2 years) for descriptive statistics. Visit year was evaluated as both a continuous and a categorical variable. Prostate cancer patients were categorized as either having visited the MPCC before or after the clinical trial enrollment initiative began in 2006. Residence was categorized as either within the Houston ten-county metropolitan area or outside of the metropolitan area. The Houston-Sugar Land-Baytown Metropolitan Statistical Area consists of Austin, Brazoria, Chambers, Fort Bend, Galveston, Harris, Liberty, Montgomery, San Jacinto and Waller counties. Prostate cancer risk group was categorized by National Comprehensive Cancer Network criteria as low-risk (clinical tumor (T) stage T1a-T2a, Gleason score ≤ 6, and PSA <10ng/ml; high-risk (clinical, stage T3-4, Gleason score ≥ 8 or PSA > 20 ng/mL); or intermediate-risk (all others).⁷

Descriptive statistics were generated to characterize the study cohort. Chi-square statistic was used to compare categorical variables. Univariate and multivariate logistic regression evaluated the association between covariates and enrollment in a clinical trial. Results are reported as odds ratios (OR) and adjusted OR (AOR) with 95% confidence intervals. P-value less than 0.05 was considered statistically significant. Analyses were conducted using SAS 9.2 (Cary, North Carolina).

Results

Patient characteristics

A total of 1,370 men with localized prostate cancer were seen in the MD Anderson MPCC between 2004 and 2008 and subsequently received treatment at MD Anderson. The median age at the time of visit was 64 years (interquartile range 57.6-69.5). The majority of men were white (83%), and lived in the Houston Metropolitan area (70%, Table 2). Thirty-two percent (442) of men had low-risk disease, 49% (674) had intermediate-risk disease, and 19% (254) had high-risk disease. Of the 1,370 patients, 326 (24%) were seen in MPCC before the 2006 enrollment initiative began, and 1,044 (76%) were seen after the enrollment initiative was implemented.

Table 2. Characteristics of 1,370 men seen in a multidisciplinary prostate cancer clinic.

Characteristic	Distribution
Age (median (range))
Years	64.2 (41.0-86.8)
Race/Ethnicity (n (%))
White	1,132 (82.6%)
African-American	146 (10.7%)
Other	92 (6.7%)
Prostate Cancer Risk Group (n (%))
Low-risk	442 (323%)
Intermediate-risk	674 (49.2%)
High-risk	254 (18.5%)
Residence (n (%))
Within Houston metro area	419 (30.6%)
Outside Houston metro area	951 (69.4%)
Clinic Visit (n (%))
Before clinical trial initiative	326 (23.8%)
After clinical trial initiative	1,044 (76.2%)

Clinical trial enrollment

Of the total study population, 73.5% (n=1,007) enrolled in at least one clinical trial, while 28.5% (n=390)enrolled in 2 or more clinical trials.66.9% of men enrolled in laboratory studies, 17.9% enrolled in QOL studies 12.9% enrolled in novel treatment studies, and 3.7% enrolled in procedural studies.

In multivariate analysis that adjusted for age, race, residence and prostate cancer risk group, men seen in clinic after implementation of the clinical trials enrollment initiative were more likely to enroll in a clinical trial than men seen before implementation of the trial enrollment initiative (AOR 8.22, 95% CI 6.16 – 10.96, p < 0.001). Overall, the proportion of patients enrolling in clinical trials increased from 38.9% (127/326) before the enrollment initiative to 84.3% (880/1044) after the initiative. Similarly, the proportion of men enrolling in 2 or more trials increased from 10.4% before the initiative to 34.1% after the initiative. Patient enrollment increased from 25% to 80% in laboratory studies, increased from 10% to 26% in QOL studies, increased from 6% to 15% in novel studies, and decreased from 8% to 2% in procedural studies (Figure 2). Similarly, when year was evaluated as a continuous variable, men seen in the MPCC clinic in later years were more likely to enroll in clinical trials (AOR 2.33, 95% CI 2.07 – 2.62, p < 0.001 per year increase).

Figure 2.

Patient enrollment in clinical trials before and after the clinical trial initiative.

Patient age at the time of MPCC was also found to be associated with clinical trial enrollment. Older patients were less likely to enroll in clinical trials than their younger counterparts (AOR 0.97, 95% CI 0.95 – 0.98, p < 0.001 per year increase). 79% of men younger than age 64.2 years were enrolled in a clinical trial while only 68% of men age older than age 64.2 years were enrolled in a clinical trial.

Multivariate analysis also identified a trend for patients in the highest prostate cancer risk group to be more likely to participate in clinical trials than low-risk patients (AOR 1.43, 95% CI 0.96 – 2.13, p = 0.083). However, unadjusted absolute differences were small with 74.4 % of high-risk patients and 73.5% of low-risk patients participating in clinical trials.

Discussion

Our Center noted a significant increase in clinical trial enrollment, related to referrals from the MPCC, after the introduction of the clinical trial initiative. We believe that the success of this initiative can be attributed to the structure of the multidisciplinary clinic which incorporated a collaborative approach to recommending clinical trials at the time of each specialists' consultation, in a clinic designed for long counseling visits, in which all treatment options are discussed while providing detailed patient education on the appropriateness of a recommended trial. The initiative also included posting information about specific protocols and eligibility criteria in the clinic area for physician reference, the addition of an advanced practice nurse to facilitate clinic visits, a patient-specific summary letter of treatment recommendations that included a list of “Recommended Clinical Trials,” trial-specific print information, and same-day consultation with clinical trial research teams.

Notably, after the trial initiative began, clinical trial enrollment in our MPCC increased across multiple trial types which included trials evaluating investigational treatments and systemic agents, trials evaluating quality of life, and trials that collected and banked blood and tissue for future study. The largest increase was observed in trials that collected and banked blood and tissue for future study. Patient-related time and travel inconveniences can be an obstacle to trial enrollment⁸; we speculate that this aspect of trial enrollment increase at our center was in part due to efforts to minimize additional patient effort as banked blood was collected in combination with PSA assessments and prostate tissue was retrieved if patients were agreeable at the time of scheduled prostatectomy.

Lack of physician and patient awareness of available trials have been identified as barriers to clinical trial enrollment.⁵ Increasing physician and patient awareness of available clinical trials through postings in clinic and inclusion of “Recommended Clinical Trials” in the summary letter provided to patients at the completion of the multidisciplinary prostate cancer clinic are key reasons why our intervention was successful.

Providing clinical trial counseling and recommendations in a multidisciplinary setting that allowed for long counseling visits and collaborative decision- making also contributed to the success of the clinical trial intervention. Physician recommendation of clinical trials is known to increase trial enrollment^9,10 and most patients prefer a collaborative approach between physician and patient for clinical trial decision- making.¹¹ Wallace et al successfully increased accrual to a difficult-to-recruit-for clinical trial after adding a multidisciplinary education session presented by a urologist and radiation oncologist as part of the recruitment process.¹²

Factors beyond patient education are also instrumental in increasing study enrollment and participation. Jacobs et al found three factors to impact increased cancer trial enrollment; dedicated research staff, recognition of physicians who consistently enrolled patients, and the number of clinical trials available for consideration.⁵ Our successful trial initiative did have dedicated staff, physicians and the clinic advanced practice nurse, and multiple trials were available for participation. Davison et al describe factors identified by patients as influential in their decision to participate in prostate cancer protocols.¹⁰ These factors varied from an altruistic intent of helping future patients diagnosed with prostate cancer, to the potential impact of study treatment on survival and/or quality of life, and the relationship and/or personal recommendation by the urologist, medical oncologist or radiation oncologist. Receiving “full and open information” to make an informed consent was also a primary influence on patient's decision to participate. Our successful clinical trial initiative offered detailed information about eligible clinical trials and provided specific written recommendations from the clinicians. Patients may attribute reservations toward clinical trial participation as concerns about not receiving standard of care treatment.⁸ However, after the introduction of the clinical trial initiative, a two-and-a-half-fold increase in enrollment in investigational treatments and systemic agents was observed at this center.

Although prostate cancer is more common among older men then younger men, we found older men were less likely to enroll in clinical trials. The discrepancy between age of patients enrolling in cancer research trials compared to the age of patients with a cancer diagnosis in the general population has been documented in other studies.^13,14 Prostate cancer is not only the second leading cause of cancer deaths in men but a disease of aging. With nearly 60 percent of new cancers and more than 70 percent of cancer deaths occurring in the 65 and older population,^2,15 advances in prostate cancer treatment are dependent on a representative sample of an older population in clinical trials. We believe future prostate cancer trials should make an effort to enroll the 65 and older population.

We acknowledge several study limitations. Availability of protocols is known to impact protocol enrollment² and the available protocols changed over the study period as protocols were continually opening and closing. It must also be noted that although we were able to identify the number of protocols that were accepted by patients per year throughout the initiative, it was not possible to document all trials offered to patients throughout this initiative. We were therefore unable to quantify the number of trials offered to patients before and after the initiative, but the number of trials patients enrolled in was similar before and after the initiative (17 various trials before the initiative and 19 various trials after the initiative), suggesting that the number of available trials was relatively consistent across the study period. We also note that although grant funding and financial support may contribute to increased laboratory investigations using patient specimens, and have a subsequent impact on trial enrollment, we were not aware of any significant financial grants or administrative support changes to our institutional infrastructure prior to or after the trial initiative. Another limitation was that although we assessed the frequency of clinical trial enrollment, we did not ask patients why they enrolled in clinical studies, so we acknowledge our inability to assess how appealing specific trials were to individual patients or if press coverage of interventions evaluated in the trials may have impacted trial enrollment. Finally, we note that the decrease in enrollment in procedural studies after the introduction of the clinical trial initiative was related to fewer procedural studies available for enrollment during that time period.

In conclusion, we believe that the increase in clinical trial enrollment to 84% in at least one clinical trial, and to 34% in 2 or more clinical trials after the start of the clinical trial initiative, highlights the impact that focused efforts for trial enrollment may make on the current national averages of less than 5% of cancer patients. The results of our clinical trial initiative provide support for the recommendation to develop a comprehensive strategy so physicians are knowledgeable of all available protocols, to educate patients regarding appropriate, disease-specific clinical trials at the time of initial consultation, and to streamline the process for clinical trial referrals to accommodate patient schedules.

Table 3.

Factors associated with clinical trial enrollment in univariate and multivariate analysis.

Characteristic	Percent enrolled in a clinical trial	Univariate analysis		Multivariate analysis
		OR (95% CI)	p-value	AOR (95% CI)	p-value
Age
Per year increase	----	0.97 (0.95-0.98)	<.0001	0.97 (0.95, 0.98)	<.0001
Race/Ethnicity
Caucasian	73.9%	Reference group		Reference group
Africain-American	76.0%	1.12 (0.75-1.68)	0.572	0.94 (0.59, 1.48)	0.779
Other	65.2%	0.66 (0.42-1.04)	0.074	0.56 (0.34, 0.94)	0.027
Residence
Within Houston metro area	81.4%	Reference group		Reference group
Outside Houston metro area	70.0%	0.54 (0.40-0.71)	<.0001	0.80 (0.58, 1.10)	0.176
Prostate Cancer Risk Group
Low-risk	73.5%	Reference group		Reference group
Intermediate-risk	73.1%	0.98 (0.75-1.29)	0.887	1.16 (0.85, 1.58)	0.346
High-risk	74.4%	1.05 (0.74-1.49)	0.799	1.43 (0.96, 2.13)	0.083
Clinic Visit
Before clinical trial initiative	38.9%	Reference group		Reference group
After clinical trial initiative	84.3%	8.41 (6.37-11.10)	<0.001	8.22 (6.16-11.0)	<0.001