A biomarker is any physical characteristic of the human body that can be measured. Your blood pressure is a biomarker. A hemoglobin level is a biomarker.
Some biomarkers can be linked to a particular diagnosis, to disease outcomes, or to respond to medication or other therapy. In oncology, important biomarkers that can be measured include the DNA, RNA, and protein within a tumor. These biomarkers can be used to make a diagnosis, predict cancer aggressiveness, or predict that a particular therapy will be effective.
The term “biomarker”, a portmanteau of “biological marker”, refers to a broad subcategory of medical signs – that is, objective indications of medical state observed from outside the patient – which can be measured accurately and reproducibly.
Here is a list of biomarkers measured in Lab Me:
Most of our at-home blood tests contain some or all of these:
Lab Me’s at-home CBC (complete blood count) with differential contains the following biomarkers:
Get the ultimate CBC cheat sheet here.
In addition, Lab Me's at-home blood test measures novel biomarkers for neurotransmitters. These are:
Read more about how they work here.
In your Lab Me dashboard, you are also able to track biomarkers such as:
Medical signs stand in contrast to medical symptoms, which are limited to those indications of health or illness perceived by patients themselves.
There are several more precise definitions of biomarkers in the literature, and they, fortunately, overlap considerably. In 1998, the National Institutes of Health Biomarkers Definitions Working Group defined a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”
A joint venture on chemical safety, the International Programme on Chemical Safety, led by the World Health Organization (WHO) and in coordination with the United Nations and the International Labor Organization, has defined a biomarker as “any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease”.
An even broader definition takes into account not just the incidence and outcome of disease, but also the effects of treatments, interventions, and even unintended environmental exposure, such as to chemicals or nutrients. In their report on the validity of biomarkers in environmental risk assessment, the WHO has stated that a true definition of biomarkers includes “almost any measurement reflecting an interaction between a biological system and a potential hazard, which may be chemical, physical, or biological. The measured response may be functional and physiological, biochemical at the cellular level, or molecular interaction.”.
Examples of biomarkers include everything from pulse and blood pressure through basic chemistries to more complex laboratory tests of blood and other tissues. Medical signs have a long history of use in clinical practice—as old as the medical practice itself—and biomarkers are merely the most objective, quantifiable medical signs modern laboratory science allows us to measure reproducibly. The use of biomarkers, and in particular laboratory-measured biomarkers, in clinical research is somewhat newer, and the best approaches to this practice are still being developed and refined. The key issue at hand is determining the relationship between any given measurable biomarker and relevant clinical endpoints.
Biomarkers assays are becoming increasingly important in clinical development. Biomarker assays are also useful for identifying intermediate endpoints of success to decrease follow-up time. The use of a specific biomarker assay can provide an early indication of drug efficacy.
Biomarkers depicting prodromal signs enable earlier diagnosis or allow for the outcome of interest to be determined at a more primitive stage of the disease. Blood, urine, and cerebrospinal fluid provide the necessary biological information for the diagnosis. In these conditions, biomarkers are used as an indicator of a biological factor that represents either a subclinical manifestation, stage of the disorder, or a surrogate manifestation of the disease. Biomarkers used for screening or diagnosis also often represent surrogate manifestations of the disease.
Since at least the 1980s, the necessity of using biomarkers as surrogate outcomes in large trials of major diseases, such as cancer and heart disease, has been widely discussed. Factors such as the increasing prevalence of cancer and heart disease increased awareness and acceptance of diagnostic tests, Lab Me provides biomarkers-related reagents as mentioned above.
The assumption has frequently been made in study design that biomarkers can be used broadly, once they become established in narrow research contexts. However, this scientifically unsound approach to trial design has in past decades led to flawed research conclusions, several of which have been considered in greater depth in review articles on the topic.
For years, researchers used suppression of arrhythmias as a surrogate endpoint for decreased morbidity due to cardiovascular disease, resulting in the approval of antiarrhythmic drugs (e.g., encainide, flecainide, moricinze) that later trials actually found to increase patient death in certain patient populations.
More recently, a large and well-publicized trial of the combination of two cholesterol-lowering drugs, ezetimibe, and simvastatin, highlighted the risk of relying too much on biomarkers: although the combination treatment lowered subjects' cholesterol levels more than simvastatin alone, it did not lead to any improvement in atherosclerosis or overall mortality, calling into question a great deal previous research that depended on the assumption that lowering cholesterol necessarily lowered morbidity and mortality.
In both these cases, as in many others, despite the best biological and statistical evidence, biomarkers that were “validated” even in a series of previous trials were found to be poor predictors of clinical outcomes.
This means that doctors can not rely on biomarkers alone in the clinical decision process. Instead, a more comprehensive look has to be employed. This can include subjective and objective findings, biomarker tracking (increased data), and additional clinical endpoints.
Without confirmatory clinical endpoint analysis, the overreliance on biomarkers, even ones previously considered validated in particular treatment contexts, presents a serious and persistent risk of producing misleading, and in some cases dangerous, erroneous conclusions.
Biomarkers play a critical role in improving the drug development process as well as in the larger biomedical research enterprise. Understanding the relationship between measurable biological processes and clinical outcomes is vital to expanding our arsenal of treatments for all diseases, and for deepening our understanding of normal, healthy physiology.
Since at least the 1980s, the necessity of using biomarkers as surrogate outcomes in large trials of major diseases, such as cancer and heart disease, has been widely discussed. The FDA continues to promote the use of biomarkers in basic and clinical research, as well as research on potential new biomarkers to use as surrogates
Biomarkers could only serve as true replacements for clinically relevant endpoints if we completely understood the normal physiology of a biological process, the pathophysiology of that process in the disease state, and effects of an intervention – pharmacological, device, or otherwise – on these processes.
Since we rarely if ever have the full picture of those types of processes, since there are always more details we don't know or understand, biomarkers as surrogate endpoints need constant reevaluation. Studies using biomarkers should always have as ultimate measures clinical outcomes, at least for retrospective analysis of biomarker correlation success.
Without continual reevaluation of the relationship between surrogate endpoints and true clinical endpoints, we risk again approving whole classes of drugs that either have no additional benefit or, worse, that harm the patient.
Biomarkers play a critical role in improving the drug development process as well as in the larger biomedical research enterprise. Understanding the relationship between measurable biological processes and clinical outcomes is vital to expanding our arsenal of treatments for all diseases, and for deepening our understanding of normal, healthy physiology.
Reference
