What is PROBE?

PROBE stands for Patient Reported Outcomes Burdens and Experiences. It is a long-term study aimed at measuring outcomes patients deem relevant to their health status and quality of life in patients with hemophilia A and B. To gather data, it uses a questionnaire that is completed by patients themselves.

What is the main goal of the PROBE study?

The main goal of the PROBE study is to give hemophilia patient organizations patient-reported data on patients’ health status and quality of life that they can use to advocate for better care and treatment.

In the past, clinical research data and the personal stories of people with hemophilia were all that was available to try to convince health authorities to make improvements in care and treatment. More and more, patient-reported data are being requested by health authorities. The PROBE study is a way to provide this data and make a stronger evidence-based case for better care.

Can the PROBE study be used to measure patient-reported outcomes for von Willebrand disease (VWD) and other bleeding disorders?

Not at this time. The initial PROBE questionnaire is designed for people with hemophilia A and B, including carriers. The PROBE team hopes to develop similar questionnaires for VWD and other bleeding disorders in the future.

What does the PROBE study measure?

PROBE collects the following types of patient-reported information:

  • type and severity of hemophilia
  • type and history of treatment
  • years of schooling
  • employment status and health impact on work
  • marital status
  • number of children
  • use of pain medication
  • impact of acute and chronic pain on daily living
  • ability to conduct activities of daily living
  • need for mobility aids
  • joint range of motion
  • history of joint surgery
  • number of bleeds in the last year
  • other health problems

Additionally, the EuroQol 5-Dimensions 5-Level instrument (EQ-5D-5L) is administered as part of the PROBE survey. EQ-5D-5L is a standardized (non-hemophilia specific) measure of overall health status and the following quality-of-life indicators:

  • mobility
  • self-care
  • activities of daily living
  • pain/discomfort
  • anxiety/depression.

The PROBE questionnaire is also administered to family members and friends of people with hemophilia. These people from the same country and background serve as a control group. This allows the study to answer questions such as, “Does hemophilia affect the number of years of schooling of people with hemophilia compared to the general population?”

Who runs the PROBE study?

PROBE is an investigator-led study. The investigators are:

  • Mark W. Skinner, Institute for Policy Development Ltd., Washington, US
  • Randall Curtis, Factor VIII Computing, Berkeley, California, US
  • Neil Frick, National Hemophilia Foundation, New York City, US
  • Alfonso Iorio, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada
  • Michael Nichol, School of Policy and Planning Development, University of Southern California, Los Angeles, US
  • Declan Noone, Irish Haemophilia Society, Dublin, Ireland
  • Brian O'Mahony,Irish Haemophilia Society, Trinity College Dublin, Dublin, Ireland
  • David Page, Canadian Hemophilia Society, Montreal, Canada
  • Jeffrey Stonebraker, Poole College of Management, North Carolina State University, Raleigh, US.

Who funds the PROBE study?

PROBE is funded with grant / research support from:

  • Baxalta, now part of Shire
  • Bayer Healthcare
  • Biogen
  • Novo Nordisk (HERO)
  • Roche
  • Sobi

PROBE receives project support from the National Hemophilia Foundation in the United States.

How was the PROBE questionnaire developed?

The PROBE questionnaire was developed with direct patient involvement in the survey design. Many versions of the questionnaire were tested with patients to make sure that key information was captured accurately. Experts in survey design and validation are part of the team of investigators.

As of early 2017, the questionnaire had been translated into 22 languages for 20 countries.

The first phase of the study in 2015 tested the feasibility of having the questionnaire administered by the National Member Organizations (NMOs) of the World Federation of Hemophilia. Seventeen NMOs participated: Argentina, Australia, Brazil, Canada, France, Germany, Hungary, Ireland, Italy, Japan, Mexico, New Zealand, Netherlands, Spain, United Kingdom, United States and Venezuela. More than 700 surveys were completed. All seventeen countries successfully administered the questionnaire and collected the responses.  This phase confirmed the content and clarity of the PROBE questionnaire, robustness of study methodology and ease of administration.

The second phase of the PROBE study conducted in 2016 and 2017 assessed the validity and reliability of the questionnaire using statistical analysis. This work was done in two parts.  The first assessed reproducibility across an identical cohort of individuals surveyed three times.   A high degree of validity and reliability was demonstrated. The second part of this was designed to assess reliability with repeat administration to population samples with a country.  The population sampling was conducted in Australia, Brazil, Canada, Mexico, Poland and Vietnam.  Over 1300 surveys were collected for Phase 2.

How is the PROBE questionnaire administered?

The questionnaire can be administered via paper surveys at patient organization meetings. The completed surveys are then sent to McMaster University in Canada for entry into a secure computerized database.

Participants may also be recruited to participate via email, a website or social media.  The questionnaire can then be completed directly via an on-line portal.

Both methods (paper and web-based) have been demonstrated to be reliable and may be used in combination.

How long does it take to answer the survey?

Seventy percent of the respondents completed the questionnaire in under 15 minutes. Ninety percent of the respondents completed it in less than 20 minutes. Only 2% took more than 30 minutes.

How old does one have to be to complete the questionnaire?

There is no minimum age. People with hemophilia as young as 11 have successfully completed the questionnaire. One has to be old enough to understand the questions and provide answers.  The questionnaire has been assessed for readability to the equivalent of a U.S. eight-grade level.

Parents or caregivers cannot complete the questionnaire for the person with hemophilia.

How is personal information protected?

The questionnaires are anonymous. The completed surveys are sent to a secure database at McMaster University in Canada. Individuals’ data are not identified and will not be published. Anonymity is protected.

Who analyzes the data?

The PROBE investigators, with help from study staff retained at the National Hemophilia Foundation, analyze the data collected.

What do patient organizations receive in terms of information?

Patient organizations receive a data set with information from their own country, with comparisons to their region and to the rest of the world.  A web-based data dashboard is in development.  The PROBE study team and staff are available to assist patient organizations in interpreting the data for local use.

What kinds of questions will the PROBE study answer?

These are a few of the questions the PROBE study should answer:

  • In a given country, compared to the general population, how does hemophilia affect a person’s ability to be educated?
  • In a given country, compared to the general population, how does hemophilia affect a person’s ability to be employed?
  • In a given country, how does chronic pain affect the ability of a person with hemophilia to conduct activities of daily living?
  • How does the quality of life of a person with hemophilia compare with other people in the same country who do not have hemophilia?
  • How does the level of treatment provided in a country affect the health status of a person with hemophilia, compared to other countries in the region and the rest of the world?
  • In a given country, how many bleeds occur annually in a person with severe hemophilia on prophylaxis compared to a person receiving treatment “on-demand?”

The PROBE study dataset provides the ability to analyze outcomes patients’ deem relevant to their life (e.g., pain, independence, education, employment, family life, mobility, current health status) in relation to or in combination with a range of demographic and personal characteristics (e.g., treatment. treatment history, disease severity, other health conditions).

Comparisons may be done over time within a country, between countries, a region or globally, or with those not personally effected with a bleeding disorder.

How often should a country collect data?

Patient organizations may want to administer the survey to a large group of people every one or two years. With time, this may allow them to show changes in patient-reported outcomes as care and treatment evolves.

How much does it cost for an NMO to be part of the PROBE study?

There is no fee for a patient organization to be part of PROBE. Those that have participated report minimal staff and volunteer time are required.. Organizations would need to pay printing costs for paper surveys and the mailing costs to send completed surveys to McMaster University in Canada.

Where can you get more information?

If you have questions or would like more information about PROBE, you may directly contact the PROBE investigator team:

Email: info@probestudy.org