Research

Learn About ALS Research

Research terms can sound precise while still leaving important questions unanswered. These explainers are designed to help readers understand what a study is asking, what it measures, and what a result can—and cannot—show.

Trial phases and study types

Observational study

Researchers observe participants and collect information without assigning an experimental treatment. Examples may include natural-history, biomarker, genetic, imaging, longitudinal, and presymptomatic studies.

Sources: Learn About Studies · ClinicalTrials.gov Glossary

Sources: Learn About Studies · ClinicalTrials.gov Glossary

Placebo, randomization, blinding, and endpoints

Blinding or masking

Participants, investigators, outcome assessors, or combinations of these groups may not know which intervention a participant receives. An open-label study does not use blinding; single-blind and double-blind are common masking descriptions.

Sources: Learn About Studies · ClinicalTrials.gov Glossary

Endpoint

An endpoint is a predefined outcome used to evaluate what happened during a study. ALS examples may include ALSFRS-R change, survival, time to ventilation, respiratory measures, biomarker changes, muscle strength, or quality-of-life measures.

Sources: Learn About Studies · ClinicalTrials.gov Glossary

Sources: Learn About Studies · ClinicalTrials.gov Glossary

What is the ALSFRS-R?

The ALS Functional Rating Scale–Revised is a validated clinical scale used to monitor functional disability in ALS. It evaluates 12 functional areas involving speech, salivation, swallowing, handwriting, cutting food or handling utensils, dressing and hygiene, turning in bed, walking, climbing stairs, breathing difficulty, orthopnea, and respiratory insufficiency.

ALSFRS-R is frequently used as an outcome measure in ALS clinical trials, but it is not the only measure of disease progression. A score is a clinical measurement, not a personal forecast.

View original ALSFRS-R validation paper

Sources: The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function

Biomarkers

What a biomarker is

A biomarker is a measurable biological characteristic that may provide information about disease activity, response to treatment, or another biological process.

Sources: ClinicalTrials.gov Glossary

ALS biomarker examples

  • neurofilament light
  • neurofilament heavy chain
  • blood biomarkers
  • CSF biomarkers
  • imaging markers
  • electrophysiology
  • digital biomarkers
  • gene-specific molecular biomarkers

Sources: ClinicalTrials.gov Glossary

Sources: ClinicalTrials.gov Glossary · FDA approves treatment of ALS associated with a mutation in the SOD1 gene

Understanding trial results

When reading a result, look beyond a headline or a percentage. Ask what the study was designed to measure and whether the result was large enough, reliable enough, and meaningful enough to change care.

  • What was the primary endpoint?
  • Was the primary endpoint met?
  • How large was the treatment effect?
  • Was the result statistically significant?
  • Was it clinically meaningful?
  • How many people participated?
  • How long were participants followed?
  • What were the safety findings?
  • Were subgroup analyses prespecified?
  • Was the study randomized?
  • Was it placebo controlled?
  • Were results peer reviewed?
  • Were full results published or only announced?
  • Did the sponsor report absolute numbers or only percentages?
  • Is this evidence from Phase 1, Phase 2, or Phase 3?

A positive biomarker result is not automatically the same as proven clinical benefit.

A failed primary endpoint should not be presented as a successful trial because a secondary or exploratory endpoint looked favorable.

Sources: How to Read a Study Record · ClinicalTrials.gov Glossary

Expanded Access

Expanded access, sometimes called compassionate use, is a pathway that may allow a person with a serious or immediately life-threatening condition to receive an investigational product outside a clinical trial when certain criteria are met.

Expanded access is not the same as participating in a randomized clinical trial. The product remains investigational, and its safety and effectiveness may not be established. The manufacturer must agree to provide it, a physician is involved, and FDA and IRB requirements may apply.

Read FDA expanded-access information for patients Read FDA expanded-access guidance

Sources: Expanded Access · Expanded Access: Information for Patients · Expanded Access Guidance

Right to Try

Right to Try is a separate federal pathway for certain eligible patients with life-threatening diseases who have exhausted approved treatment options and cannot participate in a clinical trial involving the eligible investigational drug.

FDA does not approve each individual Right to Try use, manufacturers are not required to provide a drug, and the treatment is not proven effective. An eligible investigational drug generally must have completed a Phase 1 trial, remain under active development, not be FDA approved for any use, and meet other statutory criteria.

Read the FDA Right to Try information Review FDA treatment-access options

Sources: Right to Try · Learn About Expanded Access and Other Treatment Options

Sources & Further Reading

These source cards link directly to the original material. External websites open in a new tab.

Clinical trial information is provided for education and navigation. Inclusion on this site does not mean a study is appropriate for a particular person or that an investigational treatment is safe or effective. Eligibility is determined by the study investigators using the official protocol.

Last reviewed: 09-30-2026