Precision Medicine: Its Impact on Clinical Trials and Orphan Drugs

Precision medicine, as the name suggests, aims to provide tailored treatments to specific subgroups of patients. By studying patients’ specific genetic makeup, as well as the treasure trove of patients’ medical data from analog and digital sources, researchers are becoming better equipped to determine which patients are best suited to benefit from trial drugs.

And it’s plain to see that precision medicine has many advocates, with the global market set to hit $85.5 billion by 2025, growing at an annual rate of 9.9 percent, according to Grand View Research.

In this post we explore the often interchangeably used terms of precision and personalized medicine, what they mean for clinical trials and how patients are set to benefit — with the caveat that data security remains a pertinent concern.

Definitions of Precision Medicine

The National Institutes of Health calls precision medicine “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.”

Dr. John Danaher, president of Elsevier Clinical Solutions, adds to this definition by noting the practical components of the precision medicine approach, such as as gathering patient data — genomic and other — from EMRs, EHRs and imaging systems to answer clinical questions more precisely.

It’s the large amounts of patient data available that can quickly be analyzed, visualized and plotted that is, in part, driving the precision medicine market. Patient data can be used to determine how patients’ symptoms, conditions and medical histories correlate with key clinical problems and treatments — and this can often only be understood by analyzing data collected over long periods of many years.

The effect is that researchers have, in essence, a single very large clinical trial, Danaher explains.

His theory is supported by the NIH’s $55 million funding initiative launched in 2016 for its All of Us program, the goal of which is to collate data for 1 million patients from multiple populations and sources.

The Aim and Principles of Precision Medicine

Precision medicine tailors treatment to the individual characteristics of a patient, so is also more precise about how treatment affects particular patients. And this has the obvious impact of being better equipped to recruit the right patient groups. For instance, a patient may be chosen for a trial — not because of their specific health condition — but because of their particular genetic makeup that could render them more susceptible to treatment.

The focus of precision medicine is to approach patients’ syndromes with the mindset that clinicians are treating the specific causes of a disease in a particular patient, explains the team at MedPace.

The principles of precision medicine, then, are to start with the syndrome, assign patients into subtypes based on their genetic diagnosis and choose a targeted therapy to treat that specific subtype. This approach is familiar to those developing orphan drugs: A genetic mutation causing a rare disease is specific to the genetic subgroup of patients, and needs to be the focus of treatment.

Two Ways Precision Medicine Will Change Clinical Trials

There was a recent medical case of a toddler with a rare neurological disease, which confused the child’s medical team, says David B. Goldstein, professor of medical and surgical research and director at the Institute for Genomic Medicine at Columbia University Medical Center. His team sequenced her genome and determined that the child’s disease stemmed from the non-functioning of a transporter of a vitamin.

Without precision medicine, it’s very possible the young patient would not have been successfully diagnosed and treated.

This new approach to medical care will likely affect clinical trials in two ways, Goldstein adds. The first is more targeted treatments tested on patients with specific genetic mutations; the second is that gene testing or sequencing will help to determine subtypes of diseases.

He uses the example of a trial investigating epilepsy. One drug might be tested on a large group of patients with different subtypes of the disease. Investigators will then be able to determine which subtype the treatment is best suited for.

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Biological Samples To Become More Important

Precision medicine’s growing prominence will render biological samples such as urine, blood, cells, DNA and RNA more valuable in treatment, explains Dr. Rico Berger, senior director at life sciences consulting firm and CRO, Parexel.

Berger says that more than 60 percent of PAREXEL’s clinical data for biomarker-based, precision medicines are from biological samples. This shift will require a keen understanding of how samples can be used and for what purposes. Mishandling samples, Berger cautions, can lead to compromised trials.  

But there is also the issue of consent. How the samples will be used, how long they will be stored, and for what purposes the samples can be used after the trial must be agreed to with the patient and recorded in the Informed Consent Form. Compliance is complex but essential given how much the industry is increasingly coming to rely  on gathering and managing biological samples.

Why Precision Medicine is Being Pursued

The clinical research industry has seen a fairly recent shift from symptom-based definitions of common disorders to understanding, on a molecular level, that they are biochemically distinct syndromes, explains Dr. Roger D. Klein, J.D. et al at the Regulatory Transparency Project.

The same symptoms can be caused by different molecular processes. A targeted drug can, therefore, treat one of those processes, meaning that only a certain subset of patients can benefit from it. It’s less about developing the drug and more about finding the right patients, Klein says, as the biochemical details are dependent on each patient.

Definitions of Personalized and Precision Medicine

Often used interchangeably, precision medicine is actually better thought of as the step beyond personalized medicine, Jo Cavallo at The ASCO Post writes.

Using the term precision medicine rather than personalized medicine removes the incorrect notion that treatments are sought and developed uniquely for each patient. Precision medicine identifies targeted treatment approaches for patient subgroups, based on their genetic variations, differing environments and lifestyles.

While the difference may be subtle, it is useful to realign the promise of genome-based treatment with the current reality that many patients face, including those with advanced forms of cancer.

Targeted drugs have been around since the late 1990s, but the pace of development is increasing as is the number of patients that can be matched to treatment based on the genomic makeup of their tumor.

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Links Between Rare Diseases and Precision Medicine

Rare diseases affect more than 25 million people in the US, writes professors Holly K. Tabor and Aaron Goldenberg at the AMA Journal of Ethics. This population is impacted by more than 7,000 rare conditions, each with an incidence of 1 in 200,000 or fewer.

The challenge with rare diseases is that funding is difficult to secure, given the small population sizes. Yet the way data is collected and analyzed in the precision medicine approach suggests this challenge can be met.

Precision medicine, with its use of big data, has already been applied to developing therapies for heart disease, diabetes, and high blood pressure, Tabor and Goldenberg explain. The value of precision medicine is that it purposefully seeks treatment based on patient-specificity. So those with rare diseases are key study population, especially as it will facilitate the development of orphan drugs.

Personalized/Precision Medicine and Rare Diseases Share The Same Designs

Developments in personalized medicine and rare diseases are analogous, says application scientist Katrin Flatscher. Orphan drug therapies, therefore, fit closely into the progress of personalized medicine. Indeed, rare diseases and personalized medicine are largely focused on finding treatment that can be tailored to the individual — or the individual subtype. Personalized medicine, however, is not constrained to focus on rare diseases only.

The parallel between the two is important. As Flatscher notes, if the clinical research community cannot develop the right kind of orphan drugs for rare diseases, what hope is there to apply personalized medicine to broader populations?

Aligning Stakeholders’ Desires

There are many multi-state and single state projects underway to collate patient data from multiple sources, including EHRs, to facilitate developments in precision medicine, explain researchers Kadija Ferryman and Mikaela Pitcan at Data & Society. Examples include: the All of Us research program; the Million Veterans program; the American Heart Association’s My Research Legacy; and Verily’s Project Baseline.

But the pursuit of data is not necessarily unified with multiple stakeholders expressing differing desires, Ferryman and Pitcan say. For instance, data could be seen by some as costly or risky, while others view it simply as extra work and not something of value.

Also, the data required for precision medicine to develop raises questions about privacy and security, diversity and inclusion, and equitable access, note the researchers. There is concern that de-identified medical data can be re-identified, rendering current protection against data breaches inadequate.

Concerns aside, a data-focused approach is also aligned with a patient-centric approach. This is because patients are becoming more engaged in trying to find potential treatment options and they see their personal data as being a highly valuable asset in doing so.

The goal of the clinical research community has always been to provide the best possible treatment for patients. With the medical advancements that make precision medicine possible, it’s reasonable to expect the quality of treatment will continue to rise. Data concerns amid an integrated data platform will be a concern for years to come, but this should not cloud the clear skies of promise precision medicine brings.  

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