Paving the Road to Clinical Trial Participation: Removing Road Blocks and Directing Patients Toward Novel Therapies

Abstract

Clinical trials are the key to the development of safe and effective therapy. Within the sphere of oncology, where patients are in desperate need of therapies that effectively control disease, clinical trials play a uniquely significant role in patient care compared to other therapeutic areas. After joining the Division of Oncology at Washington University in St Louis (WUSTL) in 2007, I wanted to understand the mechanics of clinical trial operations at our institution so that I would be prepared to conduct my own clinical studies. After hearing my senior colleagues’ complaints about the lengthy and tedious regulatory process required to open a trial at our institution, I realized that this is an unfortunately common phenomenon. The laborious and exhausting process in opening the U.S oncology trials has been well described and clearly dissected by Dilts et al1–3. While my area of clinical focus is gastrointestinal malignancies, my research has gravitated toward novel therapeutic development in pancreatic cancer. Patients with pancreatic cancer have a poor prognosis with a 5-year survival rate less than 5%5. In my opinion, everyone with pancreatic cancer should be presented with the opportunity to participate in a clinical study, as the standard therapy is simply not good enough. To improve patient access and awareness of clinical studies in pancreatic cancer at WUSTL, I set two goals for myself; the first was to decrease the time required to open a pancreatic cancer trial and the second to improve the clinical trial participation rate. To fully understand the challenges at our institution and to get some ideas on other institutions outside of US, I worked with Kristina Williams, one of our research managers, to compare the processes involved to open oncology trials at WUSTL to those at University of Torino (UT) in Italy, a comparable institution in Europe. Based on our retrospective reviews on recently conducted thoracic oncology trials, the median times from submission to open a trial was significant longer at WUSTL compared with UT (163 days vs. 112.5 days; p=0.048). Additionally, the median number of patients accrued per trial was lower in WUSTL (7.4 vs. 37)4. Unfortunately, our results are fairly consistent with those reported in the literature3. Although our study only included thoracic oncology trials, the result of the study reflected a more generalized phenomena experienced across therapeutic areas. In our opinion, no additional studies are needed to show that the oncology clinical trial system is broken. The key is how to identify ways to improve the system. WUSTL and the Siteman Cancer Center have made conscience efforts to shorten the length of oncology trial activation since 2010. After a careful process review, opportunities for improvement were identified and the institution began reaching out to the various stakeholders to identify ways to increase efficiency. As an example when reviewing the process in 2010, a single scientific review committee (SRC) met once per month to review all research protocols conducted in the oncology patient population. The meeting was identified as a bottleneck, as protocols received too near the submission deadline were required to wait four weeks for the next available meeting. Having identified this concern, research administration worked with the Siteman Cancer Center to add a second SRC meeting two weeks after the traditional meeting date. Having two meetings per month, as opposed to one, helps reduce the amount of time between protocol receipt and submission while simultaneously enabling the review of a larger volume of studies. Research leadership has also developed relationships with our local institutional review board (IRB) to brainstorm ways the groups can work together to improve efficiency. A fast track program has been developed to allow the concurrent submission of select protocols to our SRC and IRB if the protocol meets specific criteria. The studies that met these criteria in 2014 obtained approval in an average of 37 days- a marked improvement over the 163 days noted in 20104. In addition, research leadership now tracks all pending trials as they are actively moving through the approval process to identify and address barriers in real time, heightening awareness and improving collaboration among our financial, contractual, and regulatory teams. The shortening and simplification of the regulatory and administrative procedures has ignited the interest of not only clinical researchers, but also pharmaceutics companies. Given the regulatory process improvements, my focus has shifted to my second objective- improving the trial accrual rate. It has been estimated that 5% of pancreatic cancer patients participate in a clinical trial6 and the majority are not even referred for clinical studies. This begs the question- what factors are playing a major role in trial accrual? I personally think that the quality of the clinical study carries the most weight, therefore, carefully selecting pancreatic cancer trials for each stage of pancreatic cancer has been a priority for our program. With the increased use of the internet, patients have become very sophisticated at navigating various cancer websites to look for novel treatment options and research opportunities. Innovation is the buzzword for the majority of my patients. For example, we have a trial using a Listeria CRS-207 vaccine at our institution. Patients are willing to travel considerable distances specifically for this study because they want the opportunity to receive the most innovative therapies available. Social media and the internet play an increasingly important role in engaging patient perspectives on cancer therapy. I have noticed that more than half of my patients have visited the Pancreatic Cancer Action Network (PANCAN) website, and some of them have regular communications with PANCAN personnel specifically regarding clinical trials. It is quite refreshing to see patients coming into my clinic with a stack of clinical trial printouts in hand courtesy of PANCAN. In addition, patients, their family, and friends collect information from TV programs, Facebook, Twitter, and cancer-related websites. Several years ago, patients came to me asking for drugs that can potentially target “cocoon”. They understood the concept that pancreas tumor cells are residing in stoma, the cocoon, based on discussions boards and resources that they had found on the internet. Now, patients are initiating similar conversations regarding immunotherapy approaches. Media exerts a powerful influence on patients seeking specific clinical studies, and it certainly has the potential to improve patient participation rates. Our multidisciplinary clinic has been a tremendous help in term of screening patients for clinical studies. If patients with borderline resectable and locally advanced pancreatic cancer are seen by surgeons, radiation oncologists and medical oncologists at the same time and the recommendation for treatment is consistent, then the patient is more likely to consider the clinical study. Many of our patients are very enthusiastic about trials when they are consistently discussed and recommended by all of their providers. Prescreening and frequent communication with patients is another important factor in patient enrollment. Patients with pancreatic cancer have a narrow window for clinical studies, as protocol criteria limit when and in what circumstances patients are eligible to participate. Manual screening for new consults every week has helped potentially eligible patients for trial, which has shown to be effective way to improve clinical trial accrual7. Insurance has also historically been a barrier to clinical trial participation8, particularly for those patients seeking to enroll on early phase trials. To address this, our institution has assigned designated personnel to assist in the clinical trial appeal process. By employing a skilled set of individuals knowledgeable in this area and training staff on how to most effectively interact with insurance providers, we have been able to increase the number of approvals. The implementation of the “Affordable Care Act,” which supports patient enrollment to clinical trials, has also helped increase our approval rate- a trend which we expect to continue as grandfathered plans become less common. With the new processes we have implemented, social media penetration into daily life, innovations in technology and novel drugs, it is becoming easier to accrue patient to clinical studies within the pancreatic cancer program at our institution. Patients come to me inquiring about clinical trials and they are very committed to the trials that appeal to them. As a result, in 2012, the pancreatic cancer therapeutic trial rate at WUSTL exceeded 35%. While I am pleased by our progress, developing a successful clinical research program is an ongoing endeavor. Investigators must continually seek out novel clinical trials that help meet the needs of their patients. Centers must be intentional about engaging available social media outlets and patient advocacy groups to understand patient interests. In addition, investigators and administrators must continually evaluate for potential opportunities to improve the administrative aspects of the process.