Clinical Trial Definitions

The following are selected terms that appear in the text of the NEALS website or are meant to provide background on topics discussed on the NEALS website.

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Adaptive design- Type of trial design in which it is preplanned when data will be looked at and reviewed (interim review) and changes may occur to the study design based upon the interim review. This may help decrease time in between trials or phases.

ALSFRS-R- Amyotrophic Lateral Sclerosis Functional Rating Scale (revised); assesses the impact of ALS on activities of daily living.

Biomarker- A marker of disease or response to therapy that might be used to diagnose ALS, monitor disease progression, or monitor treatment effectiveness; they may take the form of molecules in body fluids or changes on imaging tests, such as MRI.

Biorepository- A collection of stored biological samples. Carefully collected and stored samples are critical for scientists to conduct research on disease mechanisms, causes, and for developing disease biomarkers. They are the foundation of research.

Cerebrospinal fluid (CSF)- Clear colorless fluid that occupies space in and around the brain and spinal cord to protect them from injury; an important source of testing to identify biomarkers.

Cohort- group of people sharing common factors e.g. age, gender, diagnosis.

Crossover-design- Type of trial design; a randomized, trial where group one receives treatment A and group two receives treatment B, then at a predetermined point the groups switch treatments.

Dementia – a group of symptoms characterized by a decline in cognitive (thinking) functioning that is severe enough to interfere with activities of daily living.

Double-blind- Trial design feature; neither the researchers nor the research participants know which participants are getting active medication and which are getting placebo. At the end of the trial, the “blind is broken,” and the researchers and patients find out who received active treatment.

Electromyography (EMG)- An EMG involves a series of tests, including both nerve conduction studies (NCS) and needle electromyography (needle EMG), that measure nerve signaling and muscle response.

Familial ALS- ALS that is passed down from one generation to the next due to a genetic mutation. Only 5-10% of ALS cases are familial.

Humanitarian Device Exemption (HDE)- Approval by the FDA to allow a company to market a device to a specific disease or condition (usually rare or uncommon) in the absence of evidence from a clinical trial to determine effectiveness.

Humanitarian use device (HUD)- A device marketed for a specific population under the FDA designation of HDE.

Informed consent- A person’s voluntary agreement to participate in research based on adequate knowledge and understanding of relevant information. Informed consent is documented in the informed consent form. Before signing a form, participants should always be sure to ask as many questions as needed to feel fully informed.

Interventional trial- Type of a trial; a clinical research study in which exposure to the potential therapy being tested, (eg a drug), is assigned; used to determine the effectiveness of a treatment or intervention.

Interventional trial with drugs and a placebo- Compares the effect of the treatment to the effect of a placebo; One group receives the treatment, the other receives the placebo. Everything else is held the same between the two groups, so that any difference in their outcome can be attributed to the active treatment; considered the “gold standard” because this design allows statistical evaluation of an effect; the FDA typically requires 2 controlled trials showing benefit before approving of new treatments.

In vitro- In an artificial environment outside the living organism, such as a test tube.

In vivo- In a living organism, such as a mouse or human.

Laminectomy- Operation that removes a small piece of bone surrounding the spinal cord to release pressure on a nerve root or on the spinal cord.

Lumbar puncture- Procedure performed in an exam room used to collect cerebrospinal fluid (CSF). The patient lies on his/her side or sits upright during the procedure. Numbing medication is used to numb the skin.

Mesenchymal (stem cells)- Stem cells that are derived from the participant’s own bone marrow and then readministered to the same person from which they were taken. These cells are able to mature into different cell types.

Neuroprotective- Treatments that may protect the nervous system against weakening, illness, or degeneration.

Non-invasive- Non-surgical procedure, non-phlebotomy.

Observational study- Type of a trial in which enrolled participants are observed. Outcome measures (eg measures of strength or function) may be part of the observation. No treatment is given; often used to learn about trends of symptoms or the course of a disease.

Open-label design- Trial design feature; both researchers and patients know that the patient is receiving an active treatment no placebo.

Open-label extension- Trial design feature; at the conclusion of a randomized, placebo-controlled trial, all participants are invited to take the active study drug, regardless of whether they were on active study drug or placebo. Typically researchers continue to gather information from participants during the open-label phase. If a drug is shown to be ineffective or unsafe, the open-label extension is closed.

Parallel design- Type of trial design; a randomized, interventional trial, in which one group receives only treatment A and another group receives only treatment B. In contrast to Crossover design (See Definition)

Pharmacodynamics- refers to the effects of a drug on its target in the body. As an example, the pharmacodynamic effect of a cholesterol-lowering drug is measured by testing cholesterol levels in people taking the drug.

Pharmacokinetics- refers to the level of a drug in the body and the speed at which the body metabolizes and eliminates a drug. As an example, the pharmacokinetics of a drug can be followed by drawing blood to check the level of the drug in the blood.

Placebo- An inactive substance that looks and tastes like the tested drug but has no known effect on the disease under study (eg ALS); sometimes called a “sugar pill” or “dummy.”

Placebo-controlled trial- Type of trial design; participants are assigned to one of two (or more) groups, either receiving active therapy (sometimes at different doses) or placebo. Everything else is held the same between groups, so any difference in their outcome can be attributed to the active treatment.

Randomized- Participants are randomly assigned to one group or the other; each participant has just as much of a chance as any other participant to receive either the treatment or placebo.

Selection design- Type of trial design; may speed the search for effective drugs through simultaneous testing of multiple drugs, usually without a placebo; allows for rapid development through researchers choosing the most effective and safest for further trials.

Sporadic ALS- Disease occurs at random with no genetic link; no clearly associated risk factors have been identified; patients with sporadic ALS do not pass the disease on to their children. 90-95% ALS is sporadic.

Stem-cells –Cells that have the potential to develop into different types of cells, and possibly repair cells in the body.

Tetraplegia – Paralysis from illness or injury that leads to loss of the use of all limbs and torso.

Time to event- Trial design feature; In placebo-controlled trials using this design, participants are assigned to a treatment group (active study drug or placebo) and followed in the study until they reach a pre-specified “event” (eg, “event” may be defined as a decrease in the ALSFRS-R of 6 points). If a participant reaches this “event,” he/she will enter an open-label extension (see definition).

Trial Phase- Experimental therapies, including drugs, pass through 3 trial phases of development prior to FDA approval. The objectives are different for each trial phase:

  • Phase 1: This is the first time the drug is given to humans. Prior to Phase 1 testing, a large amount of work is done in animals to understand drug safety and dosing. In Phase 1, the drug is given to a small number of people to evaluate its safety in a single dose.
  • Phase 2: The drug is given over a longer period of time at a number of dosages. Safety is further evaluated. The most effective dose is identified. Preliminary information about effectiveness may be gathered.
  • Phase 3: The drug is given at a single dosage (or sometimes two dosages) and compared to placebo. The goal is to test whether the drug is effective, so Phase 3 trials are the largest, often including many hundreds of participants at many research centers around the country or internationally. Phase 3 results are evaluated by the FDA when deciding whether a drug is safe, effective, and should be approved for sale.

Vital capacity- Maximum amount of air that can be expelled from the lungs in one breath. It is measured by a spirometer, and then scored as a percentage of the expected volume for a person based on gender, height and age. Vital capacity is often used as an outcome measure in clinical trials.