4 Unique Challenges of Oncology Trials
According to a 10-year oncology research study conducted by the Biotechnology Innovation Organization (BIO), only 5.1% of new cancer drugs tested in Phase I were likely to receive Food and Drug Administration (FDA) approval. While the success rate in moving from Phase I to Phase II was 63%, the transition to Phase III plummeted to 25%.
Additionally, in 2021, a literature review estimated the average capitalized research and development (R&D) costs per new cancer medicine at between $944 million and $4.54 billion. Typical clinical development timelines for anticancer drugs average an estimated 6.7 years, with biotechnology-derived products potentially adding another year or more.
Oncology research is unique in many ways, including the challenges researchers face.
Organizations conducting oncology clinical trials face challenges distinct from the rest of the research community. Often, medical innovations are first explored in oncology research (e.g., cell and gene therapies), with other therapeutic areas then pushing it further.
Because of this, oncology researchers may only have access to minimal existing scientific literature related to cell-based data and animal testing to predict an investigational therapy’s effect on human factors. This can make it more difficult to anticipate safety risks in advance, especially in earlier research phases, possibly making it difficult to properly inform participants of the potential risks. It can also potentially drive up net costs of the research.
Complicated Conditions and Targeted Treatments
Cancer treatment is moving toward more targeted therapies: As researchers identify cancer molecular pathways and targets, it’s becoming possible to treat the target tumor regardless of the organ of origin. More targeted therapies may change which patients and cancers may benefit, since a given treatment may only impact very specific biomarkers and genetic profiles.
Platform-type studies aiming to open and close cohorts quickly based on surrogate endpoints can help explore these targeted therapies more efficiently. These study designs often include multiple sub-studies examining the investigational treatment’s effect on different populations and targets. Such study designs challenge sponsors, contract research organizations (CROs), and sites to manage incoming data and make and disseminate decisions. It can be a challenge for the institutional review board (IRB) as well, balancing the need for both a complete and timely review.
As clinical trial design becomes more dynamic and adaptive, studies require more complex statistics and more specialized biostatisticians to ensure study data are relevant and scientifically valid.
Barriers to Enrollment
Recent findings indicate significant barriers to enrolling patients remain in clinical trials. This exacerbates the problem of working within a limited treatment population.
Enrollment barriers may affect:
- Protocol/design factors
- Oncology clinical trials often have complex trial design due to their advanced precision medicine treatments. This can cause difficulties for many clinical research sites, ultimately leading to limitations on who might be eligible to participate, high rates of protocol deviations, and high dropout rates.
- If multiple sites in a given geographic region are conducting the same trial, they likely will compete for the same participant population, making enrollment that much more competitive.
- If a potential participant has to travel a long way to find a site offering a clinical trial, they may be less likely to participate. And if they do participate, they may be more likely to drop out prior to reaching a study endpoint.
- Participants may balk at certain protocol requirements, such as extended visits for pharmacokinetic (PK) measurements.
- A patient may not ever hear about clinical trial options if their oncologist isn’t familiar with what’s available or how to discuss clinical trials with potential participants.
- Patients may be wary of joining an experimental trial and taking on those potential risks when approved therapies are already available.
- Clinicians/Site staff
- Clinical staff who are unfamiliar with how clinical trials work may not be able to share pertinent study information with a patient. Additionally, they may be ill-prepared to answer questions knowledgeably and may not understand how to coordinate clinical care with research activities.
- Because so many oncology clinical trials take place internationally, sites and sponsors have to manage multiple regulatory agencies and review boards. This means study startup times can vary greatly.
A final hurdle faced in oncology trials is trial endpoints, or the event(s) or outcome(s) being measured to determine whether the study intervention is safe and effective. Anti-cancer therapies aim to increase a patient’s overall survival and/or their health-related quality of life. This thereby proves the drug is also clinically meaningful or beneficial.
Given the pressure to develop these anti-cancer therapies quickly, the use of surrogate endpoints over clinical endpoints is common to reduce the length of time needed for study, and to accelerate FDA approval in cases where it may take an unreasonably long time to collect the clinical endpoint data.
While surrogates are beneficial for study efficiency, they may not be as intrinsically beneficial to patients, as they are a substitute for a direct outcome measurement and may only predict clinical benefit.
For example, tumor shrinkage can be used as a surrogate endpoint for longer survival in clinical trials for drugs intended to treat some cancers. Tumor shrinkage may indicate the drug is doing something, and researchers may interpolate a shrinking tumor indicates a positive event for the patient. But when using surrogate endpoints, that benefit is not specifically supported by the trial; all we know is the tumor shrank. We don’t know if the person had a better quality of life or had a longer life.
Addressing These Challenges
While potentially significant and impactful, these challenges are not insurmountable. Thoughtful, strategic planning at the beginning of the trial can help ensure impacts are minimal. Quality systems and processes can also help prevent challenges from surfacing and wreaking havoc throughout the study lifecycle.
Engaging a strategic partner to help navigate these challenges can be quite beneficial, especially for those less familiar with the regulatory landscape. Assistance from someone who has “done it before” lets your team learn from others’ experiences and potentially avoid certain issues and pitfalls altogether.