Many people I speak with have wondered why it took so long to get a diagnosis for their rheumatologic condition. And then, once diagnosed, some who try to participate in research into the condition may be surprised to discover they are not eligible for a particular study.
Why weren’t they selected to participate in a clinical trial, even when they have the condition that’s being studied? What’s going on here?
It’s about the difference between diagnostic criteria and classification criteria.
An article published recently in Arthritis Care and Research compares diagnostic and classification criteria in rheumatology and clarifies the role of the American College of Rheumatology (ACR) for each. The authors, Aggarwal, Ringold, Khanna, Neogi, Johnson, Miller, Brunner, Ogawa, Felson, Ogdie, Aletaha, and Feldman, explain that rheumatologic conditions can be difficult to pinpoint for several reasons. First, it’s unclear what causes rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and other rheumatologic conditions. Second, these conditions affect multiple systems in the body (skeletal system, immune system, etc.). Third, symptoms may look different in different people, so there’s not one single test capable of diagnosing every person who has the condition. The authors write:
The majority of rheumatic diseases are multisystem disorders with poorly understood etiology; they tend to be heterogeneous in their presentation, course, and outcome and do not have a single clinical, laboratory, pathologic, or radiologic feature that could serve as a ‘gold standard’ in support of diagnosis or classification (p. 891).
The authors distinguish between diagnostic criteria—the collection of signs and symptoms used by doctors to diagnose and treat a patient’s condition—and classification criteria—the standardized definitions of a condition mainly used to create a uniform group of patients for clinical research. This means that even when a patient has been diagnosed with RA, she may not meet the classification criteria for RA that would allow her to participate in a survey or clinical trial.
The reason classification criteria are so specific is due to the imperatives of science. Medical science attempts to explain the cause and effect of processes that occur in the human body (e.g., introducing X chemical into the blood stream will cause immune cells to have Y reaction). In order to identify such cause and effect processes with confidence, scientists must rule out confounding variables—other factors that may have an effect on the process that’s being studied. This requires that participants in a study share as many of the exact same features of the disease as possible. The authors explain that classification criteria are “…intended to create well-defined, relatively homogeneous cohorts of patients for clinical research; they are not intended to capture the entire universe of patients but rather to capture the majority of patients who share key features of the condition” (p. 893). Therefore, for the sake of specificity, many patients who have been diagnosed with RA may not be classified as eligible to participate in a specific RA study. However, different studies have different criteria. So if you find yourself ineligible for one study, you may be included in the next one.
The ACR has a Subcommittee on Classification and Response Criteria whose members are responsible for creating classification criteria for rheumatologic conditions. As described above, these criteria help guide rheumatology researchers in setting up scientifically sound clinical trials. But the ACR and Subcommittee will not fund or endorse the development of diagnostic criteria. This is because diagnostic criteria have several special challenges:
- Diagnostic criteria must be general enough to represent all the various potential manifestations of a disease. This is referred to as “heterogeneity.”
- Diagnostic criteria need to have very high specificity (to include only the people with the condition of interest) and high sensitivity (to include every person with the condition of interest). Approaching 100% for both specificity and sensitivity is difficult.
- There are currently no gold standard diagnostic criteria for most rheumatologic conditions. Gout is one example where testing for the presence of monosodium urate (MSU) crystals in the affected parts of the body is a gold standard for disease diagnosis.
- Physicians diagnose patients over a period of time using a complex process with multiple steps. A single set of diagnostic criteria is not adequate to reflect this process.
- Diagnostic criteria are often based on the local prevalence of a disease as well as other diseases that a physician is ruling out when deciding on a diagnosis. Given the number of clinical practices in various geographic settings, this would be nearly impossible to capture in a single set of diagnostic criteria.
In short, one advantage of separating diagnostic from classification criteria is that diagnosis is based on the physician’s care for an individual patient. As the authors note, “…because disease features are typically not identical among patients with a given disease, classification are not 100% accurate, thus leaving a certain proportion of patients misclassified…Only physicians considering features of an individual patient, beyond those represented in the classification criteria, in addition to extraneous factors (such as the local prevalence of conditions that are included in the differential diagnosis) can establish a diagnosis for an individual patient” (p. 893).
In an ideal world, classification and diagnostic criteria would match exactly, making it easier to identify, study, and treat rheumatologic conditions. Until a gold standard is identified, working with a rheumatologist over time is the best means of arriving at a diagnosis. And to learn about research opportunities you may be eligible for, take a look at the “Opportunities” feature of CreakyJoints patient-powered research network at www.ArthritisPower.org.
Aggarwal, R., Ringold, S., Khanna, D., Neogi, T., Johnson, S.R., Miller, A., Brunner, H.I., Ogawa, R., Felson, D., Ogdie, A., Aletaha, D., and Feldman, B.M. (2015) Distinctions between diagnostic and classification criteria? Arthritis Care and Research, 67, 7. pp. 891-897. DOI 10.1002/acr.22583