The main goal of biotech and pharmaceutical companies is to bring new drugs to market. Typically, companies spend hundreds of millions of dollars from drug discovery through clinical trials to approval. Huge focus is given to clinical trial design and patient enrichment. Those who conduct clinical trials “enrich” study populations to identify a population of patients in whom a drug effect is more likely to be demonstrable. If successful, the time it can take to collect sufficient data to support a new drug application can be shortened, bringing the overall cost of drug discovery substantially down.
Although enrichment fits well into the growing interest in “individualization” of therapy, it doesn’t mimic “real-world studies” with less restrictive entry criteria and other requirements. The question then becomes – has patient enrichment lead us even further from patient centricity? A new hurdle we now face is facilitating the availability of treatment while protecting patient safety and avoiding interference with the development of new drugs. Consequently, in the process of preferentially selecting for clinical trials that can generate data that may lead to the approval of products and wider availability, we have limited access to most.
Paradigm Switch from Product-Centric to Patient-Centric
As the patient-centric movement evolved, companies began to organize around the needs and characteristics of patients. Companies created new patient-centered business models and established patient engagement as a core focus. This led to the adaptation of many patient-centric approaches from protocol design to technology. Patients were involved in early discussions on protocols, reviewing visit structure and informed consent development.1,2
“We can align protocols to patients’ lives while still focusing on meaningful unmet needs.”
Patients became key stakeholders as they helped train site staff to create better treatment environments and advised on the management of their diseases and conditions.1,2 Patient engagement expanded as companies began to welcome patient feedback. This led to the creation of social media and mobile technologies, wearables and mHealth. Digital technologies were piloted in clinical trials as patient engagement tools to promote recruitment and retention.
Technology also played a role with patient matching registries and data mining companies. Communication channels opened to promote and accelerate direct to consumer advertising and increased sharing of clinical trial information.1 Data transparency was a priority. Companies focused on trust and confidence of patients, collaborating on decisions, and building a foundation of true patient centricity.
The current landscape of patient-centric companies and organizations shows that patient engagement activities are continuing to rise. Considering that patient centricity and patient engagement weren’t given much attention until five or six years ago, we can take these results as a whole that clinical operations managers, directors, and staff believe that the patient centricity movement is intact and engagement activities are the necessary path to take.3
In fact, 49 percent of provider executives said revamping the patient experience is one of their organization’s top three priorities over the next five years. Top investments include online bill pay and scheduling, digital communication tools, facility improvements, social media presence, 24-hour nurse hotline, remote patient monitoring, caregiver tools and support, care manager services, digital product support and interactive patient engagement systems.4 PwC highlights the industry shift toward patient centricity as a best practice, but also indicates that health care organizations still have hurdles to overcome.
Impact vs Reality
Patients and advocates are becoming empowered to take a more active role in health care, and the digital world is altering the way people seek information. Patients are educated and knowledgeable about treatment options. They are investing time in learning about their disease, locations where trials are being conducted and clinical trial results through the internet. Clinicaltrials.gov currently lists more than 270,000 studies and receives an average of more than 170 million page views per month.5 Yet, only 3 percent of oncology patients participate in clinical trials even though 75 percent are very willing. Patients are self-identifying for clinical trials only to later discover they are not able to participate. They have difficulty with eligibility due to past treatment regimens, stage of diagnosis or the presence of advanced disease.
Although barriers to participation are a focus with patient centricity, the rate of trial participation has not changed substantially over time. Cancer rates continue to rise yet very few participate in clinical trials. Growing pressure to reduce research costs has led to a huge focus on clinical trial design and patient enrichment.
Patient Enrichment and Study Design
Companies are designing studies with increasing eligibility requirements. They are using patient characteristics to enrich for prognostic and predictive results. Advancements in technology and diagnostic tools has also led to a surge in genomic and proteomic selection. While eligibility must be sufficiently inclusive to target meaningful populations, these exclusions make clinical trials less accessible. In fact, trials are often criticized for having eligibility criteria that are too narrow. This is such a hot topic that the FDA held a public meeting on April 16, 2018 to evaluate the inclusion and exclusion criteria in clinical trials.6
Key topics included the risks and benefits of participation, rationale for eligibility criteria and the impact of exclusion criteria on high risk populations. 7 While some enrichment models are used for safety purposes, increased eligibility criteria is restrictive and limits access. Preferential selection does not translate to real life and studies with too restrictive criteria lack real world evidence. It is not surprising that another topic covered during the FDA-held public meeting was looking at opportunities for using data from expanded access trials.
What about Expanded Access?
One method to ensure true patient centricity is to increase awareness and knowledge about expanded access and as an industry increase our commitment to providing therapies to patients in need. Expanded access is a mechanism for individual patients to access treatment. They strike a balance between pre-approval and fulfilling unmet patient needs. Although some criticize the program for competing with ongoing trials, it provides the option of collecting “real-world” data outside of a clinical trial setting and offers the opportunity to develop a network of physicians who have experience with the treatment. 8
The FDA has taken a stand on expanded access with the passing of the 21st Century Cures Act, legislature designed to speed approvals, boost research funding, and incorporate the patient’s voice into FDA’s decision making.9 It requires all manufacturers of investigational drugs for the diagnosis, monitoring, or treatment of serious diseases or conditions to publicly disclose their policies for how and under what conditions they will or will not make available their investigational products.10 Now is the time for pharmaceuticals companies to establish and disclose their policy and how they are going to implement. We can no longer side step public mistrust. We need to bring innovations to patients faster and more efficiently.
Industry Progress Forward
Patient engagement is a popular topic as industry leaders make their mark on changing the way we run clinical trials. Beyond advisory boards and advocacy groups, vendors and clinical trial supply companies are paving the way to support expanded access. They offer solutions for data collection, supply chain and program support. Observational data collection and innovations like wearables, mHealth, and analysis of Real World Data (RWD) are becoming standard practice. Companies are harnessing genetic testing to match patients to targeted therapies.
Knowledge built from supply chain companies who have been providing comparative sourcing, labeling and biosimilar services for years can be applied to the needs of today. Delivery of drugs to patients locally and internationally and systems for monitoring study drug adherence are readily available for integration to existing systems. Implementation of expanded access programs may seem challenging with limited resources. However, industry service providers have stepped up to provide support with program design, feasibility, understanding laws, stakeholder engagement, and connections to regulators and policymakers.
“While the initiation and management of an access program can be challenging and requires careful assessment and planning, the benefits to patients, healthcare providers and sponsoring companies are immeasurable” – Rob Fox
According to Phrma , there are currently more than 800 new anticancer drugs in the development pipeline. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the U.S. alone.10 Cancer is a major public health problem worldwide and it is up to industry to choose to invest time and resources in expanded access. I began with the question to sponsors, have we gone too far? Maybe we haven’t gone far enough.
*The views portrayed are solely those of the author.
**The author would like to acknowledge Dan Wasserstrom of CLINIGEN and Eli Lilly’s Gretchen Randlett for their contribution during the research phase of this article.
- Sharma, NS. Patient centric approach for clinical trials: current trend and new opportunities. Perspect Clin Res. 2015, 6(3):134-138.
- Steel, Abbe. A culture of patient centricity: using a model of co-creation to optimize clinical trials. Clinical Researcher. April 2015.
- Henderson, L. Patient engagement: are we there yet. Applied Clinical Trials. 2018, 27(2).
- PwC Health Research Institute. Top health Industry issues of 2018: a year of resilience amid certainty. 2018.
- Trends, charts, and maps. Retrieved from https://clinicaltrials.gov/ct2/resources/trends
- Evaluating inclusion and exclusion criteria in clinical trials public meeting. Federal Registrar. 2018, 83(2).
- FDA announces public meeting on evaluating inclusion and exclusion criteria in clinical trials on April 16. Retrieved from http://www.policymed.com/2018/03/fda-announces-public-meeting-on-evaluating-inclusion-and-exclusion-criteria-in-clinical-trials-on-ap.html
- Clinigen Survey. What your peers are saying about access programs. 2015.
- 21st Century Cures Act. Retrieved from https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/21stCenturyCuresAct/default.htm
- Reese-Coulbourne, J. Expanded access expectations of the 21st century cures: frequently asked questions. MK&A. 2016.
- Siegel, RL and KD Miller. Cancer statistics, 2018. CA Cancer J Clin. 2018, 68:7-30.