Research and Trials

Observational studies

Observational studies involve structured assessment and follow-up evaluation of health outcomes in a group of patients over time. The investigators do not assign the patients to a particular treatment or intervention, as in a clinical trial. Observational studies add to our understanding of the natural history of a disease and give us information about how patients are treated and how they respond to treatments.

Clinical trials

Clinical trials involve evaluation of the effects of specific interventions on human participants. Often new drugs or interventions are compared to dummy drugs known as placebos. Sometimes a new drug is compared to an existing drug. Researchers follow all participants carefully to assess the effects of the trial drug. Drug development is a highly regulated and ordered process, consisting of a series of clinical trial steps called phases. Each phase is designed to address a different research question, and all new drugs are required to proceed through all the phases in an orderly fashion.

Trials at the National Amyloidosis Centre

A glossary of terms used in clinical studies

Phase 1 trials
Initial safety trials on a new drug in humans. The aim is to evaluate common side effects, look at how the human body metabolises the drug, and establish a tolerated dosage range. Participants are often healthy volunteers.

Phase 2 trials
Phase 2 trials usually involve a small number of patients with the condition being studied. These trials evaluate drug safety in these patients and gather preliminary data on effectiveness.

Phase 3 trials
Phase 3 trials are conducted after the drug has been demonstrated as effective in small numbers of patients. These trials provide more data on the effectiveness and safety of the drug in patients with the condition. If the data is sufficient, researchers may use it to apply to the licensing authorities for marketing approval.

Phase 4 trials
Phase 4 trials are post-marketing trials carried out after a drug has received regulatory approval. These trials gather additional information about the safety and effectiveness of the drug.

Double blind
This means that neither the patients nor the researchers know who is receiving the study drug and who is receiving placebo. Drug and placebo materials are coded by an independent third party who holds the code secretly until the study is completed or a significant adverse effect requires 'unblinding.'

Informed consent
This is the procedure whereby the researchers explain all the important information about the study to the patient. They ensure that the patient understands the risks and benefits and that enrolment is voluntary. The patient then signs an informed consent form.

Multicentre
This means that the trial includes patients and researchers in several different sites, often from all around the world.

Open label
This means that both the patients and the researchers know what drug and what dose is being administered.

Placebo
A dummy or sham treatment received by the patients in the control group of a controlled clinical trial.

Prospective studies
A group is recruited and followed over time to gather data regarding a specific question. Our ALchemy study is an example of a prospective observational study. Patients with a diagnosis of systemic AL amyloidosis requiring chemotherapy are recruited at the NAC at diagnosis. Routine clinical data is collected over time to give information on treatment, treatment toxicity and outcomes.

In prospective drug trials, patients are recruited and then followed over a period while they receive a study drug. Sometimes patients receiving the drug are compared to similar patients receiving an older, established drug, or to patients receiving a placebo. Patient data collected over time provides information that can be analysed to assess the effect of the study drug.

Randomised controlled trial
Similar people are randomly assigned to two or more groups. One group (the experimental group) receives the drug being tested. The other (the control group) receives either a dummy treatment (placebo), an alternative treatment or no treatment. Researchers follow both groups to compare the outcomes in the experimental group and the control group.

Retrospective studies
In retrospective studies, data that has already been collected through medical records or in a clinical study are analysed to address a new question that the original study was not designed to address. For example, in a recent publication co-authored by the NAC consultants and by European colleagues, treatment outcomes in patients with advanced cardiac AL amyloidosis were evaluated retrospectively. Data on these patients were extracted from patient records and analysed. The results provided new information on outcomes in this particular patient group, which had not previously been assessed as distinct from the overall outcomes in all AL amyloidosis patients.

A glossary of terms used in AL amyloidosis trials

Response to chemotherapy treatment for AL amyloidosis may be assessed by the following criteria:

Haematological response - the response of the abnormal plasma cells producing amyloidogenic free light chains in the bone marrow. This assessment includes:

• Measurement of concentrations of free light chains in blood tests (serum) and in urine.
• Bone marrow biopsy.

Organ response - assessment of the body organs that contain amyloid deposits.

The different categories of haematological response are defined as follows:

Complete response (CR)

• No monoclonal protein in blood tests (serum) and urine tests.
• Normal free light chain ratio (ratio of amyloidogenic free light chains to non-amyloidogenic light chains).
• Absence of identifiable clonal plasma cells in bone marrow biopsy.

Partial response

• 50% reduction in serum M component (monoclonal protein) if concentration is over 0.5 g/dL.
• 50% reduction in urine light chain concentration if there is a visible light chain peak in the urine and over 100 mg/day.
• 50% reduction in serum free light chain (FLC) concentration if FLC concentration is over 10 mg/dL.