Registry and Enroll-HD: What You Need to Know
Enroll-HD is now rolling out in Europe, replacing the former HD study Registry. The studies are very similar, although Enroll-HD
is larger and will be unified across the world. But people who have been participating in Registry will notice some differences.
Here’s what you should know and what you can expect from the change.
Why is Registry changing to Enroll-HD?
- The Registry study only included Europe. It had a counterpart in North America, called COHORT, but the studies were run differently, so the data doesn’t exactly match up and some information is incomplete. Enroll-HD merges both studies and also includes people in other parts of the world, such as Latin America and New Zealand. It is more standardized, meaning that all the same types of information are collected everywhere. It is truly global, enrolling as many as 20,000 people on five continents.
Why does having a global study matter?
- There are a number of reasons. In Enroll-HD the data and tests are being standardized and collected the same way everywhere, so that they can be analyzed together as a whole. By putting a lot of people together in one study it should be possible to get answers that would be impossible with smaller studies – scientists call this having more statistical power. For instance, having access to the genetic background of lots and lots of different people from HD families means that scientists can delve into the genetic factors that affect the progression of the disease.“Why does person A show symptoms of HD at the age of 60, and person B, with the same number of CAG repeats, experience symptoms much earlier at the age of 45? Enroll-HD is probably our best chance of understanding that,” says Matthew Ellison, an HD family member and project coordinator for HDYO, the HD Youth Organization. In addition, comparing people from different cultures can help identify environmental factors that influence how the symptoms of HD develop and change over time.
A worldwide study that assesses a lot of participants over a number of years makes it much easier for researchers to find people who might be interested in and eligible to enter a clinical trial to test an experimental HD drug. Firstly, for a relatively rare disease like HD, it can be slow going for researchers or drug companies to find enough people to volunteer for their trial. A global study like Enroll-HD means that many more people will hear about upcoming clinical trials and recruitment will be faster, leading to trials being completed more quickly.
Secondly, having lots of clinical information on Enroll-HD participants’ disease signs and symptoms, and their biosamples, means that researchers can fine tune a clinical trial and only invite the ‘right’ volunteers: Those whose disease stage is most appropriate for the particular drug under test, or have a particular CAG length, or show particular symptoms, or have a particular body mass index, or are a certain age—all sorts of different factors. This means that clinical trials will be smarter, and can give answers about a potential drug’s effectiveness more quickly using fewer research volunteers.
Setting up a worldwide Registry of potential study volunteers is unusual for an uncommon genetic disease like HD. The hope is that it will encourage more scientists, including those in pharmaceutical and biotechnology companies, to focus on HD research to develop effective treatments.
What happens to my information from Registry?
- It will be incorporated into Enroll-HD. However, if you choose not to join Enroll-HD, your data will not become part of the new study, but will be preserved in the Registry legacy database. Later on, if you change your mind and decide to join Enroll-HD, your data can be linked up.
Do I have to provide a blood sample to be part of Enroll-HD?
- Yes. Giving a blood sample was voluntary under Registry. Now, everyone who joins Enroll-HD will be asked to provide blood. This sample will be used in genetic analysis to doublecheck the number of CAG repeats in your DNA. This is called “research genotyping,” because it is information used only by scientists researching HD. If you haven’t given blood before, the important thing to know is that you will not be told the results of the research genotyping. You will not be told your HD gene status. Even the site staff will not be told, and the results of this test will not be included in your medical records. Your HD gene status will only be included in the privacy-protected database that is not connected to any of your identifying details (see the Enroll-HD FAQ for more information about data privacy).You will also be asked for permission to use your blood sample in other studies. This part is optional. Biological samples can be an important tool to answer crucial questions about HD. For example, genetic information—beyond just the HD gene—might explain why the disease is so different in different people. Other biological information that can be analyzed from the blood will be studied in order to look for biomarkers, signs that can be used to precisely monitor the state of the disease. If you’ve already given blood as part of Registry, you don’t have to do it again, although you may be asked to volunteer a new sample, which could be used in gene modifier and biomarker studies. You don’t have to provide a urine sample.
What else will be different at the visit?
- Not much. The people at the study site or clinic that you visit will be the same for Enroll-HD as for Registry. If you’ve already given all your family history and personal history, you won’t have to go through that again—just provide updates.The tests to measure mental function and look for emotional problems are very similar, although some may be new or slightly different. Enroll-HD combines the most accurate and useful tests from both Registry and COHORT, and will also add some state-of-the-art tests that improve upon the old ones.
Some tests will actually be shorter. For example, Registry included a three-minute word fluency test in which you were asked to name words beginning with the letters F, A, and S. It will be replaced with a similar version that is only one minute long. One new test is being added called the mini-Mental Status Examination. It includes 30 questions and simple problems that assess memory, attention and concentration, like repeating a phrase, spelling backwards, or drawing a shape.
Will the visit be longer or shorter?
- The first visit will be about two or two-and-a-half hours. The followup visits after that will probably be between 45 minutes and one hour. In Registry your doctor did not have to do all the tests at every annual visit. In Enroll-HD, a core set of tests must be completed at every site for every participant at every annual visit; this is what makes the data more useful to researchers. Sites also have the option to add on additional tests that provide more information. These can bring the entire visit up to two and a half hours, but that won’t happen everywhere—ask at your site for more details.
How is my information kept private?
- The same system to protect the privacy of participants that was used for Registry will be used for Enroll-HD: Some basic personal information that you provide is used to create an “HDID”, a 9-digit code. At the clinic, your medical information that your doctors look at is under your name. But any data collected as part of Enroll-HD that will leave the site and go into the study’s database is only associated with the 9-digit ID number, and not your name. Even the people running the study at CHDI and its research partners, Outcome/Quintiles and the European Huntington’s Disease Network, can’t access names without going to the site.Blood samples are protected by another layer of privacy: Before they are sent to the repository in Italy where they are stored they get a new ID number that is separate from the HDID.
Who gets access to this data?
- Researchers all over the world can apply to Enroll-HD for access to data. A major reason for the new study is to get as many scientists as possible working on HD; more researchers working with these data and biosamples increase the chance that exciting breakthroughs will be made. As long as the researchers can be verified as working at a recognized research institution then they will be able to set-up a secure account. All potentially identifying information is removed from the data and samples that these researchers can access. Even the HDID is removed and replaced with another number as an extra layer of security to keep your identity private. Researchers also have to sign special agreements assuring that they will follow ethical standards of research and keep all information confidential. The data will not be sold.
How long will Enroll-HD last?
- It doesn’t have an official end date. The idea is for it to go on for many years, but you can quit at any point if it becomes too burdensome. “It’s important for people to know that they essentially sign up for the long haul, but they can opt out at any time if it’s too much for them,” says Ruth Fullam, a member of the European Huntington’s Disease Network, which coordinates the study in Europe. “They don’t have to carry on, and it won’t affect the quality of their care.” But the longer participants stay with it, the more valuable the data becomes, because it shows how the disease affects people over time. Having that information for many thousands of people in Enroll-HD will be the best way to quickly judge the effectiveness of any new drugs that participants volunteer to test in clinical trials.
When is the changeover to Enroll-HD happening?
- It is underway now, and spreading gradually across Europe. As of early 2016, Enroll-HD sites in Germany, the UK, Poland, Italy, Denmark, Ireland, the Netherlands and Spain were up and running, with more to follow soon. Check back at this site for updates, and for a full list, look at the map of site locations.