The Bigger Picture

I’ve spent my entire career working on blood disorders like hemophilia, and right now, we’re in the midst of a very exciting time in hemophilia research. Doctors and scientists are gradually unraveling the mysteries of the disease, identifying its molecular origins and subsequently developing ways to treat to it – first through blood transfusions and then with isolated clotting factor proteins. Now, researchers are investigating potential scientific advancements with the hope of bringing new treatments, and innovations, to this community.

As part of this, researchers are considering alternative measurements that may provide a more holistic picture of how a treatment can impact people with hemophilia and their families.

A Different View of Bleeds

The hallmark of hemophilia is uncontrolled bleeding. The key metric of treatment efficacy in hemophilia clinical trials, therefore, is how well bleeding is controlled. But different trials define this in different ways. For example, if a bleed occurred in the same location three days in a row, this may have been counted as three bleeds in some trials but only as one in others. It could be helpful to reduce this variability in clinical trial design moving forward.

The standardized definition of bleeds developed by the International Society on Thrombosis and Haemostasis (ISTH) in 2014 was an important first step, but as an industry, we can go even further in considering how to assess bleeds. One way to track bleeds in clinical trials, for instance, is by asking patients to report every time they treat a bleed. But we know from talking to the community that people don’t always treat every bleed, so perhaps there could be more information to capture.

To fill in the gaps, researchers are looking at ways to measure all bleeds, as well as differentiate among them – spontaneous, in response to injury, in the joints, or in other parts of the body. To do this, careful thought needs to be put into the approach to collecting information in trials. For example, researchers are turning to new technologies, such as smartphone apps, that allow people participating in trials to report bleeds and hemophilia treatments in greater detail and in real-time, in contrast to limited, retrospective questionnaires. Other new technologies like imaging methods may help us better identify and characterize the bleeds themselves.

Apples to Apples

In clinical trials, researchers often evaluate the safety and efficacy of a new medicine against those that are already available. With hemophilia, this comparison is complicated by the fact that treatments are given in two ways, either on-demand (episodic) in response to a bleed, or on an ongoing preventative (prophylactic) basis. Many hemophilia trials compare on-demand treatment with preventative treatment, which is an important approach. But this can be a bit of an “apples to oranges” treatment comparison.

As the field evolves, researches may consider more “apples to apples” comparisons, such as prophylactic treatment to prophylactic treatment, to better understand how well a particular type of intervention is helping to control bleeding on an ongoing basis compared to another treatment of the same type.

Comparing Treatments in the Same Person

Taking it one step further, we may even be able to look at these different types of comparisons in the same person, over long periods of time. That means measuring how well a person responds to treatment with a new medicine, compared to how they previously responded to a different treatment. This “intra-patient” comparison has the potential to reduce the variability associated with comparing bleed rates in different patients, such as disease biology, lifestyle and other factors. This approach requires gathering real-world data from patients before they begin treatment with an investigational medicine on a clinical trial. One way to do this is by collecting data from patients in a “non-interventional study,” or a study that looks at a patient in a real-life or day-to-day setting. This could allow researchers to track what a new therapy does for each individual in a clinical trial relative to the individual’s prior treatment, rather than comparing it to other individuals’ treatment.

Beyond the Bleeds

Perhaps one of the most important things is for researchers to understand how a medicine impacts a person’s quality of life, and whether they continue to live active, healthy lifestyles. In hemophilia, bleeds alone do not tell the whole story. Life with the disease can have an array of challenges that disrupt quality of life, such as episodes of chronic pain and the uncertainty of when the next bleed might occur. More holistic assessments in clinical trials, like physical activity or overall wellbeing, may be useful to more fully capture the benefit of treatment. The standard approach to measuring quality of life is through questionnaires and patient-reported outcomes. New technologies like activity trackers and health apps, however, may make it easier to collect this information and see how a treatment is affecting a person in their daily life.

Looking Forward

The landscape in hemophilia is rapidly changing, and researchers continue to work hard to develop new approaches and evolve the way treatments are assessed. This requires collaboration with the hemophilia community, doctors, scientists, advocacy groups and regulatory authorities. With new approaches to capture how a treatment may affect people across a variety of measures, in real-time and in the long-term, we can build a much more detailed and multifaceted understanding of each option. And ultimately, that complete picture is what can empower doctors and people with hemophilia to make more informed decisions in this exciting new era of hemophilia research.