. He can be reached at jupton@advanstar.com.

Julian Upton

	While last week’s Patient as Partners EU conference in London (January 27–28) was primarily focused on patient involvement in designing and executing clinical trials, a number of takeaways and observations are relevant in the wider pharma context, especially for an industry that is increasingly committed-in theory at least-to the concept of patient centricity.

	The patient-involvement obstacles faced by those designing and conducting clinical trials, of course, pre-empt or echo the practical, ethical, and logistical challenges that other sectors of the industry must tackle in realizing a truly patient-centric culture. At present, it was pointed out, more than 80% of clinical trials experience delays of one to six months and a mere 10% of trials are completed on time. What’s more, 48% of clinical trial sites “underperform,” failing to deliver the number of patients expected; and, although it varies by therapeutic area, on average, only half of all patients screened complete clinical trials. Engaging patients in clinical trial design could help to alleviate some of these problems, leading to improvements, for example, in study design, participant recruitment, participant retention, protocol adherence, and facilitating a better participant experience.

	This is all well and good, but the presence at the conference of many patients themselves, some with very debilitating conditions, served to underline a disconnect between the industry’s noble intentions and the current reality. The patients in attendance took a strident tone when it came to airing their grievances. “When it comes to trials, are you doing them 

 us?” was one patient’s question. “When designing a trial, the designers think of ‘us and them,’” said another. “That decision at the beginning informs the journey subsequently.” There was more: “Things are baked into studies that don’t address practicalities;” “Trial design focuses on limitations rather than possibilities;” and “We always hear that changes are five or 10 years into the future-we need these changes now.”

	Some of these changes come down to simple ways of phrasing a question or request to the patient. “Some people respond to ‘Take your medicine’; others would prefer, ‘Its time to take your medicine,’” observed Dumitru Drumea. More significant strains on the patient involve travel to the clinical site-in the US, 70% of patients live at least two hours away from their nearest study center-and the ongoing impact of their treatment on their families.

	These are emotional aspects of course, and emotions can be difficult to reconcile with the some of the cold practicalities of healthcare. In terms of decentralized trials (aka home, virtual, remote, or site-less trials), for example, there is the not inconsiderable issue of safety to consider. But, as many of the speakers emphasized, a patient’s emotional wellbeing 

 a significant factor in their treatment, and this of course extends way beyond the clinical trial space.

	“I have tried to bring patients and their carers into the office,” noted Liz Clark, VP of medical affairs at Norgine. “There isn’t one ‘average’ patient,” she continued. “We have to represent people with diseases, rather than ‘patients’ as an amorphous thing.” Takeda’s senior director and head of global strategic patient services, Lu Zheng, Ph.D., explained, “Clinical teams have been very focused on measurable data. But patients are human; they’re not living in a vacuum. We need to understand not just the patients’ physical pain but any emotional pain they might be feeling.” Highlighting the importance of ethnography over questionnaires and focus groups, Jeremy Sayers, managing director of Origins Insights, a company engaged in qualitative work on the patient experience, added, “There’s nothing like seeing into the eyes of the patients themselves and speaking to them in their own environment.” 

	Things are beginning to change, but slowly. “We are at the very beginning of this journey,” said Zheng. When it comes to changing a culture, “the industry is not a small speedboat,” commented Daniel De Schryver, patient engagement and advocacy lead at Janssen. “We’re talking about moving a tanker.”

Articles

Involving patients more meaningfully in the industry's activities means getting more serious about their emotional wellbeing.

Engaging with Emotions: Patients as Partners

	Biomarker research is transforming how the pharma industry approaches a number of challenging therapeutic 

areas. In oncology, predictive biomarkers have played a pivotal role in evolving what was once primarily a chemotherapy, one-size-fits-all approach to treatment into a personalized approach based on a person’s individual tumor biology.

	Translational medicine plays a critical role in advancing this emerging field of research. By providing R&D departments with the capabilities to generate better hypotheses, implement new insights in clinical trials, and accelerate their pipelines, biomarkers have been able to quickly impact the treatment landscape for patients. At Bristol-Myers Squibb (BMS), researchers are using predictive biomarkers to help identify and develop targeted treatment approaches for patients who are resistant to current immuno-oncology (I-O) therapies.

	Ahead, Saurabh Saha, MD, PhD, senior vice president and global head of translational medicine at BMS, shares his perspectives on the current biomarker landscape, the role of translational medicine in accelerating this area of study, and how BMS is working to advance biomarker research across their R&D portfolio.

Q: Can you outline the current opportunities and advancements in the biomarker market?

 Within the I-O arena, we’re actively evaluating multiple biomarkers to better understand their potential in predicting how a patient may respond to I-O treatment. We are also investigating biomarkers across other therapeutic areas, including a pro-peptide known as PRO-C3 as a potential biomarker for nonalcoholic steatohepatitis (NASH), which currently can only be diagnosed through an invasive liver biopsy, and anti-citrullinated protein antibodies (ACPA) that may help physicians diagnose rheumatoid arthritis before joint damage becomes clinically apparent.

Q: What key challenges remain in translational medicine?

 Translational medicine includes all of the activities that are necessary to profile a patient’s disease biology so we can provide the patient with as many treatment options as possible, and to increase both the speed and success of our drugs through the clinic.

	Every patient has a unique disease biology, which means there are no one-size-fits-all approaches to treating many conditions. Even with biomarkers in I-O, there is no single marker that will tell us everything; it will vary depending on the type of cancer and the status of that tumor.

	Another challenge is that in order to help streamline clinical trials and develop safe and effective therapies at a faster rate, we need to continue finding new ways to generate more actionable, testable hypotheses, while focusing our efforts on the ones most likely to succeed.

Q: What distinguishes BMS’s activities in this area from what you’ve seen in your previous roles?

 I believe what makes Bristol-Myers Squibb unique is that we invest an enormous amount of time and resources across all areas of translational medicine and push the boundaries of science. Additionally, our translational medicine team is truly a core group. Every area, from translational pathology to bioinformatics, is fully integrated across our discovery and clinical development teams, which allows for rapid, efficient knowledge-sharing and collective idea generation.

Q: As global head of translational medicine, can you outline how your activities will have global reach?

 I am responsible for overseeing our robust translational medicine program and driving early clinical development across the pipeline, with the goal of driving new compounds to clinical trials, and hopefully one day, regulatory approval. Given Bristol-Myers Squibb’s global presence, I have an excellent opportunity to drive our research and development efforts worldwide.

Q: Collaboration is of course key to translational medicine. How do you see BMS and pharma, in general, furthering its collaborative initiatives in this field?

 Solving the puzzles for challenging diseases will require a collaborative effort across multiple sectors.

	At BMS, we have more than 75 active partnerships and collaborations with academic research centers, laboratories, clinical trials organizations, and biotech firms, which complement our unique translational medicine offering. One great example of this is the International Immuno-Oncology Network (II-ON)-one of the first peer-to-peer collaborations to bring industry and academia together-which aims to advance I-O science and translational medicine through innovation. Since Bristol-Myers Squibb formed the network in 2012, the II-ON has produced data from a plethora of research projects and launched 14 biology-driven clinical trials across 22 different tumor types. Insights from these data have led to several published papers and even some of the earliest findings on a number of biomarkers.

	Another example is our participation in the Accelerating Medicines Partnership (AMP). This consortium of industry, academics and the National Institutes of Health (NIH) came together to develop new ways of identifying and validating promising biological targets for diagnostics and drug development. Through the AMP RA/SLE program, we are working with the partners to address relevant challenges for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), two key areas of focus for Bristol-Myers Squibb. The data generated from this research will be publicly available, and could potentially be applied to diseases beyond RA and lupus. 

	In the future, I imagine the focus on collaborations will continue to become more important as we work to generate insights as a collective research community. By working together, both pharma and its partners can play an essential role in advancing novel, translational science.

BMS executive shares his perspectives on the current biomarker landscape, the role of translational medicine in accelerating this area of study, and how BMS is working to advance biomarker research across their R&D portfolio.

BMS and Biomarker Research: An Interview with Saurabh Saha

	Research Triangle Park, N.C.-based Marken is a clinical trial logistics company involved in direct-to-patient services and biological sample shipments. Offering a GMP compliant depot network and logistic hubs in 45 locations worldwide, Marken is described as “the only patient-centric supply chain organization 100% dedicated to the pharma and life sciences industries.”

	Ahead, Marken CEO Wes Wheeler discusses the evolution of the patient-centric supply chain and how it is set to impact the clinical trials landscape.

What defines the patient-centric supply chain?

I think the best way of describing a patient-centric supply chain is that it is one that respects the life-saving nature of what we do, and respects the fact that we’re not just moving boxes, we’re moving a biologic sample, an organ, a life-saving drug, or a life-saving vaccine, and that we realize that there is a patient behind every single one of those shipments.

	Every protocol is different and every protocol requires a patient’s informed consent. When the patient consents 

to a study, they’re basically putting their personal data at risk, and they’re trusting that the sponsor company or the CRO will protect the privacy of the patient and all of their health data. They’re consenting to giving that data to a group of people they don’t know. So there is the concern, with direct-to-patient studies especially, that patient data that can cross country borders could end up in the wrong hands.

	We’ve taken this really seriously. In the last three to four years, we’ve developed a direct-to-patient to program, which is now extending into the cell and gene area, where we respect the fact that every protocol has an informed consent signed by a patient and that we’re entrusted to protect their data. 

What are the key challenges associated with a patient-centric supply chain?

 Data security and data privacy are the biggest challenges, when, for example, patients agree to a home-based trial or a personalized immunotherapy trial where their personal information is exposed. It’s not like the old days when you had thousands of patients in a diabetes study and the potential for an individual patient’s data to end up in the wrong place was minimized. We’re now talking about highly personal transactions. 

	We go to a patient’s home and deliver a drug, meet with a nurse, and the nurse administers the drug and maybe takes a blood sample and puts that back into the supply chain. That exposes the patient’s name, potentially, and so we’ve developed processes and procedures to ensure that all patient data is blinded in our systems, that whatever data that crosses country boundaries is encrypted, and that it’s not possible for the investigator to know what drug he or she is giving to the patient. Otherwise, you are compromising the integrity of the trial.

How are digital and AI technologies impacting the patient-centric supply chain?

I’m not sure that we are being inundated by AI technologies yet on the clinical side, but on the digital side our biggest challenge will be dealing with wearable devices, point-of-care devices. I think ultimately the use of blood as the currency for clinical trials will diminish. It will be easier to transfer a patient’s health and vital signs through a wearable device like a Fitbit, one that might be enhanced for the clinical trial to extract the patient’s pulse, blood pressure, and perhaps blood content, temperature information, maybe even biomarker data. 

	When wearable devices replace the use of blood for testing, all that data will transfer to the Internet, and so can be compromised. That’s where we have to be very careful. In the future, we will potentially be delivering wearable devices, making sure they’re calibrated properly, making sure that they are transmitted under the appropriate conditions, etc., in addition to whatever blood we draw.

How does social media/digital engagement feature as part of the patient-centric supply chain?

We are working with many companies now and have around 100 trials ongoing with a direct-to-patient feature. These are very personal transactions. A patient could be critically ill with cancer and not able to make it to the doctor’s office for treatment. We work on a training module for the drivers and we assign a project manager, who is responsible for setting up the trial, ensuring that the drivers are certified, and that the protocols are reviewed in detail. We get to know the patient by name, we can call the driver on his or her way over to the patient’s home, and we make sure the nurse is there at the same time. The nurse does his or her work, drawing and centrifuging the blood, puts it into tubes, into the box, and the driver takes it to the central lab. 

	What we’re working now, however, to make that process even better is an Uber-like technology. We hope to have this in pilot trials soon. It will offer the patient an Uber experience: they can go to their app, call up for a delivery, they can see which driver has been assigned and where the driver currently is. They can communicate with the driver, whether by phone or text message, and create that personalized experience. 

How do you see this approach evolving in the next two or three years?

I think right now every pharma company has got the message. There are some that are far ahead of others. I think in two years’ time, every single significant clinical trial will offer patients the opportunity to take part from their home. This will grow, for example, in studies with Alzheimer’s patients, Parkinson’s patients, epilepsy patients, and terminal cancer patients, who perhaps cannot drive, cannot get to the doctor’s office in time. The direct-to-patient approach will greatly increase retention and compliance among these patients, and enhance the experience for them. I think eventually that 10-20% of all patients will be treated at home.

The clear trend we see, which fits into our strategy, is that almost 50% of all trials in development right now are cancer-related, most cancer drugs are sterile, and about half of those drugs are biologically derived, requiring very sensitive handling. But the more exciting thing is the advent of cell and gene therapies, or immunotherapies. In autologous drug trials, where each patient’s tissue is used to create a drug, each treatment is personalized. There are many of these trials being developed now and we’re working with three major pharma companies as an exclusive supplier of cell and gene therapy supply chain work.  

	This is going to completely change the industry because every treatment is personalized, and requires an individual patient’s tissue to be transformed into a drug within a certain timeframe and under certain temperature conditions. It means the traditional model of making bulk product in a factory for distribution to warehouses and wholesalers will go away. We will have banks of small pharmaceutical storage areas in retail pharmacies to store a patient’s individual therapy, so when they’re ready for the next treatment, they can go to the pharmacy and they get their own personalized medicine. The system we see with the Walgreens, the McKessons and the Cardinal Healths of this world currently storing hundreds of millions of drugs in tablets and bottles will go away, and we will move toward small vials of sterile product that are personalized with the patient’s name on it. 

Q: Is pharma prepared for this transformation?

Yes and no. I see a few companies that are very bullish and working hard at this, but the majority of this work is coming through small biotechs. They’re not able to manufacture the stuff outside, they can’t outsource to a [contract manufacturing organization], for example, so they’re developing their own laboratories. 

	There’s a whole cottage industry being formed, with small companies now advertising that they can do contract manufacture of cell and gene therapies. You are going to see a whole industry created around this.

Julian Upton is European and Online Editor for Pharmaceutical Executive

Q&A explores the evolution of the patient-centric supply chain and how it's poised to impact the clinical trials landscape.

Julian Upton

Articles

Engaging with Emotions: Patients as Partners

BMS and Biomarker Research: An Interview with Saurabh Saha

The Emergence of the Patient-Centric Supply Chain