Clinical trials in Parkinson’s disease and lack of participation

Improving our treatment of Parkinson’s disease (PD) is dependent on conducting clinical trials to collect information about PD patients and to test potential new medications and procedures. However, lack of participants in clinical trials is the number one obstacle to success of a clinical trial, despite the fact that participating in clinical trials can be a very positive and beneficial experience for patients in a number of ways:

• It offers the chance to feel more in control of a disease that is usually characterized by lack of control
• It allows participants to contribute to the scientific understanding of PD, and potentially help not only themselves but others in their situation
• It offers the possibility of access to a new therapy.

The APDA website contains a lot of useful information about clinical trials. Read about clinical trial basics or watch our webinar spotlighting clinical trials in PD.

How to find out about clinical trials

The first source of information regarding clinical trials in your area should be your neurologist. He or she may even want to refer you to a clinical trial being conducted at the medical center at which you seek care.

Clinicaltrials.gov is a very useful website hosted by the National Institutes of Health (NIH) which lists all clinical trials past and present, for all conditions, and can be searched for trials that specifically address PD. You should be aware however, that the trials on the website are not vetted by the NIH and may contain trials that are not up to the standards of the United States Food and Drug Administration (FDA). Therefore, if you find a trial that is of interest to you, please discuss it first with your neurologist before signing on.

Another very useful website to know about is the Fox Trial finder – a resource run by the Michael J. Fox Foundation. Both people with PD and clinical trials can register on the site and the Trial finder matches up willing participants and trials.

Types of clinical trials

There are many types of clinical trials, mostly divided into two large categories:

Observational Clinical Trials

In this type of trial, a new treatment is not tested. Rather, the trial carefully observes a particular aspect of the disease to learn more about it. These trials may require you to donate blood or other specimens including spinal fluid (I will discuss the topic of lumbar punctures to obtain spinal fluid for a clinical trial in an upcoming blog), urine or stool. Gene testing, imaging, neuropsychological testing, and questionnaires may all be components of an observational trial.

Interventional Clinical Trials

In this type of trial, a new treatment is tested to see if it either improves a particular symptom of PD or is neuroprotective and acts to slow down the course of PD. The intervention can be any of the following:

• Type of exercise or therapy regimen
• Cognitive therapy
• Medication – either a completely new medication, a new formulation of an already approved medication, or a new indication for an already approved medication (e.g. a medication approved by the FDA for high blood pressure, and now the pharmaceutical company wants to test if it works in PD)
• Surgery
• Any other type of procedure – for example, stem cell therapy or gene therapy

Different types of trials may appeal to different people. For example, one person might be hesitant to try a medication that is not FDA approved, in which case he/she may feel more comfortable enrolling in an observational trial or a trial of an exercise program. Another person might be reluctant to commit to a trial that is simply observational and does not introduce a novel treatment. That person might be more drawn to interventional trials. People without PD can often participate as well (e.g. care partners), especially in observational trials which typically collect the same information from both a PD population and a non-PD population in order to compare the results.

Obstacles to clinical trial participation

The Frustrating Enrollment Processes

It is one thing to understand the value of clinical trials and decide that you would like to participate in a clinical trial. It is another thing entirely to actually get yourself enrolled in one. Frequently, I hear from people with PD that the process of getting enrolled can be frustrating. Here are a few reasons why you might need to be persistent:

• For an interventional trial, there are many steps that take place prior to the start of a clinical trial. The drug developers must submit an Investigational New Drug (IND) application to the FDA before beginning a clinical trial that tests the new drug. The application is very extensive and involves information about any animal and human studies already performed as well as detailed plans about how the clinical trials will be conducted.
• Once the FDA approves the IND, then the investigators need to select sites at which the intervention will be tested. Often these sites are at academic medical centers and the ones that are selected are the ones that seem likely to recruit sufficient numbers of patients.
• Before the trial can start at these sites, there are numerous groups within the institution that need to approve the trial. These include the Institutional Review Board (IRB) which is an internal body of clinicians and scientists who independently evaluate the trial to determine if it meets adequate safety requirements. In addition, the contracts between the drug developers and the academic institutions are vetted by the legal and other departments. All these processes take time before the first person can be enrolled.

Because of all these steps, the trial might be listed as officially open for enrollment, but it might not be enrolling yet at the site that is convenient for you. Ideally, the site would take your information and call you back when everything was ready to go, but it may fall on you to keep calling back.

You should also be aware that each clinical trial site typically has a contract with the drug developers to enroll a certain number of trial participants. Once that site meets its target number, it is typically closed to further enrollment. The websites that list clinical trials such as clinicaltrials.gov and Fox trial finder are not continuously updated, but rather are updated at certain intervals. Therefore, the website may say that a trial site is recruiting, but in reality, it already reached its patient limit.

In addition, each trial has inclusion and exclusion criteria. Inclusion criteria are a list of characteristics that participants in the trial need to have. These may include a particular age, time since diagnosis, medication status etc. Exclusion criteria are a list of characteristics that will keep a person out of the trial. These may include a concurrent medical illness or a certain score on a screening test. One of the main goals in clinical trial design is ensuring that the data that emerges is as clean and interpretable as possible. Practically, this means that patients may be excluded from the trial if their clinical situation is not straightforward. In addition, if a new medication is being tested, there may be unanticipated side effects. Excluding patients who have other medical problems may be necessary from a safety point of view.

Being in the Placebo Group

The placebo effect is defined as a beneficial consequence of a biologically inactive intervention. It has been clearly demonstrated in trial after trial, that patients with an expectation of improvement, will improve. Because of this effect, clinical trials typically have a control arm in which participants do not receive the active drug, but rather an inactive drug (in addition to their standard PD treatments that they continue to receive). This allows for comparison between the two groups and a determination of how much the medication under investigation helps above and beyond the standard of care.

I have heard many patients say that they are reluctant to join a clinical trial because they may end up in the placebo group. Here are a few points to consider concerning this argument:

• The goal of a clinical trial is for researchers to know whether the substance being tested is better than an inactive substance. This may not be the case and the placebo group may end up doing better than the group receiving the medication under investigation.
• The placebo effect has genuine positive effects that could be beneficial to a trial participant
• Participating in a trial in general, whether receiving placebo or not, means increased medical attention, due to multiple trial visits, and laboratory testing. This can be beneficial to patients as well.

Clinical Trial Registry: Improving Parkinson’s Clinical Trial Enrollment

One example of assisting with and expediting the process of finding participants for clinical trials is working well in one part of the country – with the help of APDA.

The Washington State Parkinson Disease Registry (WPDR) was established in 2007 by Drs. Cyrus Zabetian and Jim Leverenz to enhance existing and future PD research efforts in the Pacific Northwest. Funding in the first few years was provided by several PD advocacy groups including APDA and the Washington State Department of Health.  Since 2012, the APDA Northwest Chapter has been the sole funding source. WPDR serves as a model to successfully connect patients and trials in different communities across the country. Instead of opening a trial and then going in search of the perfect patients for the trial, the registry looks for the trial participants first, screens them and records their information in a database in anticipation of clinical trials that need participants. When a trial opens, a search of the registry can identify potential participants immediately.

Recruitment to WPRR takes place via local movement disorders physicians, at support groups and educational conferences and through APDA newsletters and email announcements. At the time of enrollment, clinical and demographic data are collected and are subsequently updated on an annual basis.

Since its inception, the WPDR has been used for recruitment by a total of 68 research studies conducted by 31 investigators at 8 different institutions in the Pacific Northwest. Just over the past year, the registry has been used to recruit for 26 studies.

A registry such as the WPDR requires significant ongoing work, effort and funding. It must be kept updated with current contact information and clinical PD characteristics in order for it to be useful as a clinical trial recruitment tool. New patients must be continuously added to make the registry more robust and to take the place of patients who have decided to withdraw. One of the reasons that the registry has been so successful, is that there is a collaborative atmosphere among all the movement disorders groups across the Northwest as they work together to improve clinical trial enrollment.

Tips and takeaways

• Clinical trials are always looking for willing PD and control participants, but PD patients who want to join a clinical trial may find that there are obstacles. Persistence may be required.
• Be sure to view the recent APDA webinar about clinical trials to learn more about the clinical trial process and how to get involved.
• The WPDR is a model of collaboration that has led to a successful Clinical Trials Registry that matches patients to clinical trials in that area.
• If you live in the Pacific Northwest and want to join the registry, please visit registerparkinsons.org or call 1-888-365-9901 to get started.