Oncology clinical trials are a high stakes game in the pharmaceutical business. Given that over 500,0001 Americans die each year of cancer, it is the second most common cause of death in the US and afflicts virtually every age group.
Unlike other therapeutic trials, oncology trials are more sensitive in nature and require specific clinical expertise to properly manage. Many participants are required to have already undergone front and even second lines of therapy and only if these have failed are they eligible for the experimental and toxic drugs often required in oncology trials. Costs are high, enrollment can be challenging and you are often working with medically-fragile patients. However, when managed properly, effective oncology trials can save lives, generate new revenue streams and make breakthrough discoveries in a challenging therapeutic area.
According to the American Cancer Society (ACS), more than 1.5 million new cancer diagnoses will be made 2010. While thousands of oncology drugs are being researched at any time, very few will make it all the way to market. While many barriers or reasons for failure can’t be predicted, taking control of the basics of study design and implementation can make all the difference. Taking time up front to ensure you have the right protocol, the right team and the right technology in place can streamline clinical research.
Determine the Best Eligibility Criteria
Setting eligibility criteria should start with serious consideration and an in-depth understanding of your therapeutic area. As a general rule, criteria should be defined by the primary scientific objective of the study, which is driven by an unmet medical need. Setting the criteria can be particularly challenging in oncology trials since many patients have already undergone intense treatments and may have diminished abilities to commit to the rigors of a clinical trial. In addition, the more stringent your eligibility criteria are written, the harder it may be to enroll the appropriate number of participants.
Common eligibility criteria include: specific disease state, age, gender, prior therapies, lab results, activity levels, and current and previous medications. In some cases, tissue samples are critical to the study design. In this case, it’s important to include in your eligibility criteria that the patient must either have previous tissue samples or be willing to undergo a biopsy prior to enrolling in the study.
Regardless of what type of therapy or cancer you are researching, setting effective eligibility criteria is the first step toward running an effective clinical trial.
Understanding Placebo-Controlled Trials
While the use of placebo in oncology clinical trials is rare, there are times when there is a solid rationale. Placebo-controlled trials may be appropriate for highly unpredictable conditions, for conditions where there are no effective therapies available, or when available treatments have serious side effects. Due to ethical considerations, the ability to explain this rationale is critical, particularly in markets where it is more challenging to get approval to perform placebo-controlled oncology trials, such as in Brazil or other Latin American countries. Without a comprehensive and detailed explanation of why the placebo-controlled study is necessary, chances for approval are slim to none.
Under the right circumstances, placebo-controlled trials can be very effective in getting effective therapies to market more quickly.
Choose the Right Investigator
Investigator selection is another key driver of an oncology trial’s success. Not every site is capable of running a study, even if they claim to have plenty of experience or treat a large number of eligible patients. Here are some important considerations to evaluate:
- Patients: Select an investigator with access to the specific types of patients needed for your trial. Since oncology trial patient inclusion and exclusion criteria can be very limiting, this is of the utmost importance.
- Infrastructure: It’s important that every site have the appropriate infrastructure to support the study. Depending on the study design, this could mean many different things.
- Staff: Finding investigators where the staff are engaged in the clinical research process and are well-educated on good clinical practices (GCP) makes a big difference in how well the study is run. It will also aid in getting patients enrolled if the staff believe in the benefits of clinical research.
- Relationships: Consider how you’ll be treating study participants and what testing may need to be done throughout the course of the study. If you know you’ll need tissue samples, find an investigator with access to a credible pathologist. A relationship with a respected radiology department is essential for many oncology trials in order to achieve timely and consistent tumor evaluations. And, most importantly, a team environment between the investigators’ research nurses and coordinators always yields the most successful sites.
- Location, Location, Location: Geography plays a key role in investigator selection. If you need tissue samples to be processed within 48 hours from when they are collected, considering airline schedules will be critical to the study design. If your sites can’t get necessary specimens delivered within that window of time, it doesn’t matter if they have the best staff or most appropriate patient population. It’s also important to consider competition for patients – if there are numerous studies recruiting patients with a rare diagnosis from the same investigator site, it’s probably best to consider other investigators.
Assemble the Best Team
A well-designed study is nothing without a high-performing team. It goes without saying that all members of the team should have an in-depth understanding of oncology. Furthermore, if you can bring together a team with oncology experience in the specific area being studied (ie. hematology/oncology, solid tumors, etc.), you’ll be even better off.
In clinical research, the project manger plays an integral role by overseeing the entire study process. Basic characteristics demonstrated by the best project managers include: sound therapeutic knowledge, confident, organized, with excellent interpersonal skills. In addition, with many studies spanning multiple sites, and even countries, the ability to troubleshoot and solve problems quickly are other important traits to consider when selecting your project manager.
Monitors, otherwise known as clinical research associates (CRAs), need slightly different skills. Attention to detail is extremely important given CRAs are expected to ensure the study is performed in accordance with the protocol, GCP and regulatory guidelines set forth by the FDA.
Physicians, biostatisticians and the data review team also play a key role in the study process. Doing your due diligence to ensure the strongest team members will have the greatest impact on the success of the entire study.
Engage Regulatory Experts
Understanding the regulatory landscape, which can be particularly challenging in oncology, is critical. For example, knowing how to navigate adaptive trial design, or understanding what the Food & Drug Administration (FDA) may be looking for in a study submission can save valuable time and resources. Fortunately, the FDA’s oncology division takes a collaborative approach to working with sponsors, and will often provide input on a study design.
Savvy pharmaceutical companies and CROs may elect to partner with regulatory consultants and/or quality assurance organizations to assist with navigating the complexities of the regulatory environment. Quality assurance organizations can be engaged to conduct audits to ensure GCP and quality are maintained throughout the entire study process. Engaging this type of partner early on is likely to ensure a much smoother process when the study comes to an end. Particularly today as many organizations are running leaner than ever, in an often “virtual” environment, partnering with a well-established regulatory consultant that has seen the big picture of the study from the start, can be extremely valuable.
Embrace Technology
Embracing technology can be one of the most powerful and cost-effective ways to enhance the success of a clinical trial. Technology, such that you’ll find by partnering with a digital clinical research organization (dCRO), can help to run safer trials and deliver higher quality data more efficiently. While most pharmas and CROs are using some level of eClinical technology today they often operate in silos, making processes slightly more efficient, but still worlds away from the fully-integrated system a dCRO can provide.
The benefits of using a fully-integrated technology platform for study management are significant. In fact, this summer, the National Cancer Institute expressed interest in using an Internet-based system for data collection and management in cooperative, large-scale trials, with a goal of streamlining administrative and technical processes2. The interest in using technology is increasing for multiple reasons, one of which is patient enrollment, a common challenge in oncology trials. The ability to view and monitor the number of patients enrolled at every investigator site can help ensure the study is on track right from the start. If enrollment is below expectations, study teams can adjust their strategies and quickly make decisions to help drive enrollment.
Once the study is fully underway, the ability to view data, across all sites at every level, is invaluable. The ability to quickly identify trends and potential problem areas through the use of technology can ensure trials are run as safely as possible.
It’s easy to see that each of these benefits offered through the use of technology can also reduce the total cost of the trial. Since oncology trials are among the most costly to run with extremely high per patient costs, this is an important consideration that can’t be overlooked.
In conclusion, it’s no secret that conducting clinical trials in oncology can be challenging, but the potential rewards are equally significant. With the seriousness of this clinical area combined with all the potential roadblocks along the way, savvy pharmas should do everything possible to streamline the research process – including the use of advanced technology and smart up-front decision-making.
References:
1 http://www.cancer.org/acs/groups/content/@nho/documents/document/acspc-024113.pdf
2 http://www.fiercebiotechit.com/story/nci-plans-clinical-trial-system-reforms/2010-07-20
About the Authors:
David Hinds
David Hinds is a Global Project Director at Clinipace Worldwide. He brings more than 15 years in biotechnology and pharmaceutical companies, serving in a variety of roles focused primarily on the strategy and execution of clinical programs. He has held Senior Clinical Operations positions with Exelixis, Kai Pharmaceuticals, Genentech, Genitope, and Intermune. He also worked as an Operations Manager for Pharmacia and a Lead CRA for Quintiles. Mr. Hinds received a B.S. in Biology from the Citadel and an MBA from the Moore School of Business at the University of South Carolina.
Robyn Philip-Norton
Robyn Philip-Norton is a Global Project Director at Clinipace Worldwide, and brings more than 20 years experience in the strategy and implementation of global and local clinical trials. She spent eight years in senior roles in clinical and medical development in both registration and post-market clinical trials. She has held management positions with Covance and The University of Sydney’s NHMRC Clinical Trials Centre. She received a BSc and a MPH from the University of Sydney.
About Clinipace Worldwide:
Clinipace Worldwide is a global technology-driven clinical research organization (CRO) specializing in fully-integrated clinical research services for biopharmaceutical and medical device firms. Its team of therapeutic experts brings extensive knowledge and insight into successful clinical development through proactive clinical trial management. With specific expertise in oncology, among other therapeutic areas, Clinipace Worldwide has managed over 90 contract research projects conducted at almost 3,000 sites with 100,000 patients. Clinipace Worldwide is headquartered in Research Triangle Park, NC with additional domestic operations in Overland Park, KS, and South American operations based in Brazil, Argentina, and Peru. For more information visit our website at clinipace.com.
