“Life is good,” says the wheel cover on the Jeep next to your car in the parking lot. “Good?” you think cynically. Try getting in a car with a bum knee. Or pushing a grocery cart after an elbow bleed. Hang in there, because life with a bleeding disorder can be good, even great.
The Patient Reported Outcomes, Burdens and Experiences (PROBE) study is a global survey of the quality of life for people with hemophilia A and B, and their family members. The goal of the study is to collect useful data that can improve lives. “We want to be able to have enough information to advocate for better care for people with bleeding disorders,” says Neil Frick, MS, National Hemophilia Foundation (NHF) vice president for research and medical information.
“PROBE gives a direct understanding of what living with hemophilia means to an individual patient,” says Mark Skinner, JD, the lead author of the study. “It will allow us to provide a population profile within a country.” He is former president of the World Federation of Hemophilia (WFH) and of NHF. Skinner has severe hemophilia A.
Now in its second phase, PROBE has already unearthed some interesting findings.
Nuts and Bolts
NHF is the administrator of the study. “We receive all of the funding, pay the investigators and make sure that it’s moving forward,” Frick says.
The first phase included national member organizations of WFH that had the interest and ability to conduct the survey. A total of 704 people filled out the paper questionnaire; two-thirds had hemophilia A or B and one-third were family members. They represented patient organizations in 17 countries, from Argentina to Australia, and from Ireland to Italy. Most respondents received the survey at their organization’s annual meeting.
One of the unique aspects of the study is the use of unaffected family members as the control group. “In many countries there is no comparator data available,” Skinner says. By including parents and siblings, the survey canvasses people of the same socioeconomic background to see what difference having hemophilia makes. “If everybody in a particular society has a high school education, but people with hemophilia only have a sixth-grade education, we can begin to interpret that there is an impact on educational opportunity,” says Skinner.
Phase I tested the strength of the survey. It was patterned after the EQ-5D-5L™, a standardized questionnaire developed by the EuroQol group of international researchers that measures health outcomes. Investigators needed to ensure that the survey was validated, meaning it accurately measured what it set out to measure. They also wanted it to be feasible for the societies to administer, low cost and easy to implement. The PROBE questionnaire gathers information via open text questions, such as “please describe…,” and check-off boxes. Most respondents complete it within 15 minutes.
The data are then grouped to find patterns or trends. But individuals’ data are not identified and will not be published. “Their anonymity is protected throughout the process,” Skinner says.
Surveying the Survey
The EQ-5D-5L model uses five aspects of health, called domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The questions contain five boxes describing the respondent’s current situation, from “I have no problems doing X” to “I am unable to do X.” Further, patients mark their health score on a scale from 0, the worst health they can imagine, to 100, the best health they can imagine. The domains and check boxes were used in the PROBE survey.
Refinements were made to reflect the day-to-day experiences of people with hemophilia. For instance, the PROBE survey contains a table of nine mobility aids and assistive devices. Respondents mark how often they use each. Because pain can be a constant companion in this community, there are separate sections on acute pain and chronic pain. “It goes into pain issues, what kind of medications you’re taking and whether it’s affected your work life, relationships, getting up and out of bed every day,” says Frick. Difficulties with specific activities of daily living, such as bathing, dressing and even intimacy, are also captured.
Further, the survey contains detailed questions about bleeds, treatment regimen, inhibitors and target joints. Although there is a clinical definition of target joints, patients often have their own definition. “They may think of it as a joint that is weak, prone to bleeds and problematic,” says Skinner. This was factored into the phrasing of certain questions. “We ask a couple of questions related to reductions in mobility and patient perceptions of what a target joint is,” he adds.
The investigators expected the first phase to be a trial run. With people from a variety of countries who speak various languages, it was inevitable that something would get lost in translation. Take the word “cane,” for instance. In the United Kingdom and Australia, it’s called a walking stick. “We had to localize the language, even across English,” says Skinner.
An omission that patients spotted in the first survey was the effect of hemophilia on oral health. It’s now included in Phase II. In addition, respondents can place a check mark next to other health conditions they’ve experienced during the past year. The list includes asthma, cardiovascular diseases, diabetes, hepatitis and HIV/AIDS.
Some questions were rearranged to improve the flow, says Skinner. Others were reworded to clarify instructions. In addition to paper, the Phase II survey is offered electronically via the web and iOS or Android platforms. “We want to demonstrate that regardless of which platform is used, it will give the same results,” Skinner says.
The questionnaire is distributed twice in each country to test its reproducibility, its ability to obtain similar answers each time. “That demonstrates that it is reliable,” says Skinner. Once reproducibility is verified, patient organizations could give the survey annually or after a major policy change, he says. That change could entail introducing prophylaxis, for example. “The survey would give a benchmark from the patient perspective on the impact of that change,” says Skinner.
The surveys are sent to McMaster University, in Hamilton, Ontario, Canada. “They’re set up in a secure institutional database,” Skinner says. This adds another layer of protection and privacy. Currently, administrators there are doing an internal review of a new survey-related website, which will automate the process. With the Phase II expansion of the survey into Africa, East Asia, Poland and Vietnam, Skinner estimates the need for about 22 language versions. “Those are all being built into the web platform,” he says.
Skinner has participated in enough phone surveys for hemophilia research to know what he doesn’t know—what happens to the data he volunteers. That’s where PROBE stands out in stark relief. A patient organization in Japan could conduct the survey, send it to McMaster University to upload the data and have a report within days. “We want to provide real-time, actionable data back to the patient societies,” says Skinner.
Although the study results have yet to be published, preliminary observations can be shared. For one, subjects on prophylaxis showed a 20% reduction in reporting other health issues, such as anxiety, arthritis, sleep disorders and heart disease, Skinner notes.
Further, lack of access to factor products affects more than just a person’s health. “Individuals who are not on prophylaxis don’t seem to have as long a career or productive work life,” says Skinner. They are retiring early because of health complications from hemophilia, rather than by choice, he adds.
Application and Advocacy
Trends teased from the data are expected to have a practical application. They could be used to show a government or payer that prophylaxis not only reduces bleeds, but also increases a person’s productivity. Working and providing for a family helps citizens and society. “If we’re able to validate that, then it becomes powerful and quantifiable, in terms of the impact on the individual and the economy,” Skinner says.
Comparing people with hemophilia to their peers without hemophilia may also reveal that mobility issues prevent them from getting to school or work. “The patient organization could make a compelling case why you might need a special transportation assistance program for your patient population,” says Skinner.
Once the data are published, they could be used to make country-to-country comparisons in conjunction with other data—say, from the WFH Global Survey. “The power of comparison is to see what another country has been able to do with a limited intervention,” Skinner says. The country at hand could get ideas for making life better for its own citizens with hemophilia.
What’s needed are not necessarily sweeping changes, but stepwise improvements. That’s what WFH has shown through its development model. “The great thing about hemophilia is that small interventions can make a big difference,” says Skinner. He cites the introduction of homecare as an example. “You figure out what is achievable and sustainable, and start incrementally,” he says.
Although an individual’s story of hardships and heartache with hemophilia is important, the experiences of a whole group often trigger a more pronounced response. “We are empowering patients and patient organizations to move advocacy beyond anecdote and emotion to evidence-based arguments,” says Skinner. Those arguments are much more convincing when backed up with robust data that quantify the qualitative aspects of a group. “People all over the world need data in order to advocate for their organizations,” Frick says.
The PROBE survey will continue to evolve over time. “As we move into other parts of the world, we may find other things that should be added to our check-box list,” says Skinner. There are plans afoot to make the web version of the survey more in-depth. “For people who check the hepatitis box we could drill down, and find out about liver cancer and other complications,” Skinner says.
Participating in the PROBE study benefits patients, their families and patient organizations the world over. Displaying the data graphically may help decision makers see that incremental changes can improve quality of life for people with bleeding disorders. Then people with hemophilia will be able to follow their dreams with fewer obstacles to overcome. Eventually, whether it’s Jan in Poland or Juan in Mexico, the goal is for all to be able to say, “Life is good.”
PROBE is supported by unrestricted grants from Baxalta, part of Shire, Bayer, Biogen, Novo Nordisk HERO and Sobi.