Participating in Research: Part 2

Last week's blog was the first how of a summary of a presentation by Dan Kaufer MD, of North Carolina at the 2019 International LBD Conference. It discussed the value of and need for clinical trials and their structure, design and purposes. This week we dig a little deeper and discuss the components of clinical trials and what you should know before you participate.

Clinical Trial Components:

Institutional Review Board (IRB)

1. Board members: doctors, researchers, members of the community

Tasks:

• Review, approve, and monitor all clinical research studies
• Ensure that research risks are minimized and are reasonable in relation to any potential benefits
• Review the informed consent document to make sure it is understandable and clearly describes the risks and benefits of the study

Informed Consent

Provides potential and enrolled participants information about a clinical study

• Intended to help a person make an informed decision about the risks of, potential benefits of, and alternatives to the study

A person must sign an informed consent document before participating in a research study

• Signing the document and providing consent is not a contract
• Participants may withdraw from a study at any time

Clinical Study Research Plan

A clinical study is conducted according to a research plan (protocol) that is designed to answer specific research questions and safeguard the health of participants and covers the following :

• Reason for conducting the study
• The number of participants needed
• The schedule of tests, procedures, or drugs and their dosages
• The length of the study
• What information will be gathered about the participants

What Do You Need To Know?

Many studies have strict criteria for the study and the subjects. You need to know the following before you sign up.

Study Basics

• What is being studied?
• What is the therapeutic rationale for this treatment?
• What do we know about possible treatment effects?

Subject Eligibility

• What is the target population?
• Inclusion criteria: age, diagnosis, severity, etc.
• Exclusion criteria: age, severity, prohibited medications, other medical conditions, etc.

Treatment Arms (components)

• What are the possible interventions (e.g., treatment vs. placebo) that I might receive during the trial
• How will it be determined which intervention I receive (for example, by chance)?
• Who will know which intervention I receive during the trial (blinding)?

Other Medications

• Can I take my current treatment(s)?
• Are there any medications that I am not allowed to take?
• Are there other treatment options available?

Study Requirements

• What will I have to do to participate?
• Do I need to have a study partner?
• What tests and procedures are involved?
• How often will I have to visit the hospital or clinic?
• Will I have to stay overnight?
• How long will the study last?

Cost/Payments

• Who will pay for my participation?
• Will there be an issue with my insurance company due to experimental vs. standard care?
• Will I be reimbursed for other expenses such as travel?
• Who will oversee my medical care while I am participating in the trial?
• What are my options if I am injured during the study?

Follow-Up I Termination

• What if I decide to withdraw from the study?
• What type of long-term follow-up care is part of this trial?
• If I benefit from the intervention, will I be allowed to continue receiving it after the trial ends?
• Will results of the study be provided to me? (e.g., which treatment arm, brain imaging data, genetic testing, etc.)?

Now, go find a clinical trial and join up! Just be aware that if getting a new experimental treatment is your ONLY reason for signing up, you are likely to feel cheated if you end up in the placebo group. If you look at the whole process as a way of helping the researches find out more about LBD, then getting to be in the non-placebo group can be a wonderful, but unexpected bonus to an already good adventure.

References/Resources 
Dan Kaufer MD, North Carolina
Food and Drug Administration:
Lewy Body Dementia Association
Comprehensive Clinical Trials Site
Center Watch. Overview of Clinical Trials.

For more information about Lewy body disorders, read our books:
A Caregivers’ Guide to Lewy Body Dementia
Managing Cognitive Issues in Parkinson's and Lewy Body Dementia
Responsive Dementia Care: Fewer Behaviors Fewer Drugs
Riding A Roller Coaster with Lewy Body Dementia: A Manual for Staff

Helen and James Whitworth are not doctors, lawyers or social workers. As informed caregivers, they share the information here for educational purposes only. It should never be used instead of a professional's advice.

Participating in Research: Part 1

Learning more about LBD and how to treat, or even cure takes more than researchers. It also takes people like us to step up and volunteer to be subjects. More clinical trials are ended for lack of subjects than for any other reason!  Most of the information below is from a presentation by Dan Kaufer MD, of North Carolina at the 2019 International LBD Conference.

How does clinical research differ from clinical care?

• Clinical research involves human subjects who participate in a study protocol designed to answer a question that contributes to medical knowledge
• Clinical trials are meant for research, not to administer proven effective medical care.
• Clinical research is the only legitimate pathway for developing new, safe and effective treatments for a medical disorder or condition.

Types of Clinical Research Studies

Observational:

• May be done prior to or in conjunction with a clinical trial
• Evaluates a health-related outcome
• Evaluating one or more tests aimed at identifying or diagnosing a particular disease or condition

Interventional:

• Clinical trial
• Evaluates or compares one or more therapeutic interventions for safety and potential benefits

Reasons for Conducting Clinical Studies

• To evaluate one or more tests aimed at identifying or diagnosing a particular disease or condition
• To explore ways to improve the comfort and quality of life through supportive care for people with a chronic illness
• To find ways to prevent the initial development or recurrence of a disease or condition
• To evaluate one or more interventions for treating a disease, syndrome, or condition

Drug Development Process for Human Disease

Preclinical to Clinical:

• Average time: 12 years
• Average cost: $1-2 billion
• Potential treatment identified based on laboratory studies (in vitro)
• Proof of concept studies in laboratory animal models (in vivo)
• Human testing - clinical

Clinical Testing

Phase 1.

• Less than 100 subjects.
• Average time: 2 years
• Assess safety for use in humans?
• Usually tested in normal human subjects.

Phase 2.

• 100 - 1000 subjects
• Average time: 2 years
• Assess the safety and potential effectiveness of an experimental therapy for a specific medical condition.
• Ex: What dose or delivery method provides the highest benefit and least risk.
• More then one Phase 2 trial exploring various aspects of a drug may run concurrently or may run consecutively, which can greatly increase the time for this phase.

Phase 3.

• 100s - 1000s (a.k.a. "pivotal" trial)
• Average time: 3 years
• Typically Involves testing 1or more doses of the experimental therapy In a randomized, placebo­ controlled, double-blind study to determine If the therapy is safe and effective.
• Randomized: Subjects are assigned by chance
• Placebo-controlled: Subjects receive either active treatment or placebo
• Double-blind: Assignment is not known by either the subject or investigators

Therapeutic Interventions: Regulatory Tiers
Once a therapy has passed Phase 3 Clinical Trials, it must be approved by the FDA before it can be marketed.

FDA Registered Therapies

• Pharmaceuticals (chemically based substances)
• Requires clinical research protocols that must meet high standards for scientific merit (e.g., double-blind, placebo-controlled), safety, and ethical conduct
• FDA reviews data from the Phase 3 trials (and possibly others) for regulatory approval.
• FDA approval can take over 2 years, but can be fast-tracked, with results in as little as 6 months.

Vitamins and Herbal Supplements

• Derived from natural vs. chemical sources
• Not intended to treat specific medical conditions 
• Homeopathic treatments are in this category. While they are often designed to treat specific symptoms, they are not FDA governed.
• Rigorous testing for efficacy or safety not required
• Testing and quality control depends on company standards

Therapies for Neuro-degenerative Disorders

Symptomatic

• Palliative
• focus of treatment is alleviating one or more signs/symptoms associated with the disease or condition
• potential benefit of treatment is cumulative

Disease-modifying

• focus of treatment is to alter the underlying disease process in a way that slows down or halts progression, or reverses decline
• potential benefit of treatment may be cumulative

Where Are Clinical Studies Conducted?

Academic research centers

• conduct a variety of different research studies
• perform clinical trials
• provide clinical care

Community-based clinical trial centers

• primary focus on performing clinical trials
• little or no provision for clinical care

Private practices

• primary focus is clinical care
• also conduct clinical studies

Well, you may know a lot more about clinical trials than you did but there's more to come. I know I do! But, be sure to read next week's blog before you consider volunteering. While it is a great thing to do and much needed, you need to understand what you are getting into! Next week, the last half of this series will discuss the components of clinical trials and what you should know before you participate.

References/Resources
Dan Kaufer MD, North Carolina
Food and Drug Administration
Lewy Body Dementia Association
Comprehensive Clinical Trials Site
Center Watch. Overview of Clinical Trials.

For more information about Lewy body disorders, read our books:
A Caregivers’ Guide to Lewy Body Dementia
Managing Cognitive Issues in Parkinson's and Lewy Body Dementia
Responsive Dementia Care: Fewer Behaviors Fewer Drugs
Riding A Roller Coaster with Lewy Body Dementia: A Manual for Staff

Helen and James Whitworth are not doctors, lawyers or social workers. As informed caregivers, they share the information here for educational purposes only. It should never be used instead of a professional's advice.