Expanded access, also known as compassionate use, is a subject that can stymie many pharmaceutical companies. The terms refer to the FDA program allowing pharma companies to provide patients with an investigational new product outside of a clinical trial. This might occur when a patient does not qualify for a clinical trial or there is no ongoing trial.
The decision of whether or not to make an investigational drug available to a patient can save a patient’s life, cause adverse health effects, or result in a firestorm of controversy on social media. Most companies handle the approval of compassionate use requests differently, and few likely enjoy reviewing these requests or making these difficult decisions.
For that reason, Johnson & Johnson made headlines over the summer when it decided to undertake a pilot program to change its compassionate use approach, opting to have an independent review panel consider requests made to the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen) for compassionate use of an investigational medicine that was undergoing clinical testing and was in short supply. For this pilot, requests for the medicine, Daratumumab, a treatment for multiple myeloma, were independently reviewed by a committee of internationally recognized medical experts, bioethicists, and patient representatives convened by the New York University (NYU) School of Medicine.
Dr. Amrit Ray, Chief Medical Officer (CMO), Janssen, has spoken to enough patients and had enough involvement in compassionate care decisions to know that a better system was needed for helping those people seeking access to investigational new drugs outside of a clinical trial. After many sleepless nights considering the challenges faced by patients and how the situation could be improved, Ray and J&J decided to stand up and stand out to drive a positive change and went to work.
“One of the most important things I learned as a physician is the importance of active listening,” says Ray. “We have listened to patients and their families on the question of compassionate use. They have told us that it is a very poorly defined area in general across all companies. Patients and their families often have many questions that they are not able to get answered. Questions related to topics such as how the process works, who they should contact, what information they need to provide, and how companies decide who will be provided access to a medication. When we stepped back and reflected on that, it was clear we needed to have a better process in place.”
SIMPLIFY THE PROCESS
In some biopharma companies a compassionate use request might come in through one of many different avenues, get forwarded to numerous individuals within the company, and end up with a physician involved with the medication or its clinical trials who will then decide whether to approve or deny the request. The requests might not always be handled in the same manner or by the same person. This inconsistency and variation in the process from one company to the next only increased the need for some type of structure to be deployed.
But other factors also contributed to J&J’s decision to move the review to an independent committee. “We can all see the feedback from patients that has come in the form of heart-wrenching media campaigns,” notes Ray. “Sometimes these campaigns might involve a half-million petitions. Additionally, Right To Try laws have now been passed in 24 U.S. states, and there are also discussions taking place at the international level in groups like the World Health Organization (WHO). That tells us there is a real societal need for a process that is fair and ethical and considers the needs of patients and their families in a more purposeful manner.”
CREATION OF TASK FORCE LEADS TO INDEPENDENT PANEL
In April 2014, Johnson & Johnson took the first step toward addressing these concerns and launched a dedicated Pre-Approval Access Task Force sponsored by the J&J Office of the Chief Medical Officer and empowered to take an in-depth look at the process J&J had in place. The task force, composed of leaders and colleagues from across the company, considered aspects of the process end-to-end and looked at numerous perspectives, including the needs of patients, regulatory concerns, and clinical development. The goal for J&J was to be objective and take an ethics-based, evidence-driven approach to what could make a real difference for patients.
When the idea of an independent review panel was proposed, the task force looked at several different options before landing on NYU. The responsibility for choosing panel members was left to NYU. A key goal was ensuring that potential panel members would not have any conflict of interest.
“The NYU School of Medicine set up a compassionate use advisory committee, which we refer to as CompAC,” says Ray. “The committee is made up of 10 internationally recognized bioethicists, medical experts, and, importantly, patient representatives. They reviewed the compassionate review requests for Daratumumab and did so for several months. Once they performed the review, they returned to J&J with their recommendations. We continued to take full responsibility for the final decision on whether or not to approve the request. In almost all cases, we agreed with the recommendation of the committee.” The committee reports directly to NYU, and the school receives a fee for the administration and work of its committee members.
A preapproval access decision must take into account information such as what data is available on patient safety and efficacy, populations that responded well to the medication, and the often limited availability of clinical supplies.
INNOVATION ALSO CREATES CHALLENGES
This program was designed to make compassionate use interactions easier for physicians and patients, thereby creating a new model for researchers and industry. To accomplish those goals, J&J had to figure out how to balance a multitude of factors such as evolving safety and efficacy profiles, the constantly evolving body of scientific information, the supply challenges that exist for all investigational medicines while they are still being developed, and the regulatory considerations around compassionate use.
“We made sure we thoroughly scrutinized and addressed every challenge that arose in this debate,” states Ray. “We did that using expertise both inside and outside the company. The outside input came from many sources including bioethicists, patient groups, and the NYU experts. In fact, NYU was constantly evaluating our model to make sure we were moving the pilot forward. We also shared the pilot idea with the regulatory authorities so they were aware of what we were doing.”
Throughout the process, Ray kept track of the challenges he encountered to make sure his team was able to learn from them. He felt these learnings would also contribute to a stronger model in the long term.
DEVELOP AND OPERATIONALIZE ETHICAL PRINCIPLES
There were two main goals J&J had in mind when investigating this change. “Number one, and most importantly, we knew we needed to develop a set of bioethical principles that would guide the decision making,” says Ray. “That has been done. We have agreed on the following six principles:
The second goal has to do with how those bioethical principles are operationalized and relates to the processes, technologies, expertise, and commitment within large, complex, and global organizations, to ensure that decisions are made in a consistent, thoughtful, and timely manner. Ray believes the CompAC pilot will help J&J accomplish both goals.
COMPAC SIMPLIFIES THE PROCESS FOR PATIENTS
According to Ray, the new process utilizing the CompAC panel significantly simplified the process. His team members put themselves in the shoes of the patients to figure out the best ways for their physicians to apply for use of a product. The company also directly asked a number of patient groups for feedback on what would be helpful to them and for their advice on how the process should work.
The new process allowed compassionate use requests to J&J to be submitted either via a specialized 800 number or through a dedicated email address. Both the phone number and email address were available on the Janssen website. In addition, to further help those families pursuing expanded use of a drug, on its website J&J lists the key principles relating to its compassionate use policy and offers a short video that explains what patients and families should expect during the process. Most importantly, it offers clear guidance on how patients can work with their physicians to submit expanded use requests.
One of the most frustrating situations a person can encounter is submitting a request to a large corporation and then never hearing anything back. To avoid this situation, J&J has also made a commitment to always close the loop with patients through their requesting physicians.
Ray states this is one of the biggest frustrations that he personally heard from patients. “Listening to patients who have interacted with many companies over time, they would submit a request but would often not get a response,” he states. “When they did get a response, it was often unclear to them why there was a denial. With the efforts that we are taking, we are making a commitment to patients to ensure that there is always clear, respectful information provided back to patients in a reasonable timeframe.”
MOVING BEYOND J&J
In November of 2015, J&J received approval of Daratumumab from the FDA, and it will be sold under the brand name Darzalex. With that approval, the pilot study came to an end. Although Ray could not reveal the exact number of requests that were received, he notes the pilot received positive feedback from stakeholders involved in the process, including patients and patient groups. J&J and NYU are both committed to an open pilot and publishing the findings for anyone to see. Their hope is that this pilot could be used as a model by other pharma companies and will be considered a positive step for public health.
"It was clear we needed to have a better [compassionate use] process in place."
Dr. Amrit Ray
For now, J&J is performing an independent audit of the pilot. That audit will take place over the next few months. If it is deemed to have been successful, it will be applied more broadly across the portfolio of the company. Any improvements recommended by the audit will also be considered.
Despite the best intentions of Ray and his team, there will still be detractors who believe this committee is nothing more than an attempt by J&J to take a difficult decision-making process and outsource it to an outside entity. Ray notes nothing could be further from the truth.
“When you look at what we went through to develop this pilot, you can clearly see that our primary consideration was always to do what was right for our patients. With compassionate use, patient lives will always be on the line, and that decision-making responsibility is something we take very seriously. We continue to be fully responsible for getting to the right decision on patient requests. Taking the time to develop a process that is fair, consistent, thoughtful, and patient-centric is important to every stakeholder in this process,” he concludes.