Why You Want Your Medical Test to be Validated and Based on Peer-Reviewed Research

JAMA Oncology recently published a peer-reviewed study of the efficacy of MyProstateScore 2.0 (MPS2) in determining the probability of high grade prostate cancer and whether a patient should undergo a biopsy. This study “validates” the MPS2 test, but what does that mean? And what makes clinical validation and peer-reviewed findings important designations for doctors, patients, and healthcare systems to consider when deciding to use a particular test?

A test, such as MPS2, is created and developed using data and medical information from a particular group of patients. In a nutshell, clinical validation means that the test has similar and consistent results when it is applied to data from a completely different group of patients.

Peer review is a critical aspect of scientific publishing. It involves research being scrutinized by independent experts to ensure the work is original, relevant, methodologically rigorous, and accurate.

The peer review process

Many well-known medical journals, such as JAMA and the New England Journal of Medicine, will not publish research unless it has been peer reviewed. This means that, once a research article is submitted to a journal, and the editor decides the research is important and relevant to the journal, it will be sent to other scientists who are experts on the article’s subject matter.

These peer reviewers, who usually remain anonymous to the article’s authors, carefully examine the research to evaluate its quality, how well the experiment was designed, and whether appropriate methods were used. They also look at how significant the research is, whether it will advance the field, and whether it is original or novel research.

The peer review process is one way to prevent inaccurate information or false claims from being published, and it establishes a sense of trust in the integrity of the journal and the science it publishes.

How clinical validation works

Clinical validation is an important component of research. Pertaining to a screening test such as MPS2, validation means that researchers have assessed the performance characteristics of a test. This means they have examined how accurate, reliable, and reproducible the test is. In the clinical validation study of MPS2, the authors established that MPS2 can accurately detect or predict the presence of clinically significant prostate cancer.

Researchers look for specific criteria when they validate a test, like whether it has more accurate outcomes than similar tests or can improve on existing tests considered standard. For example, researchers found that MPS2 performed significantly better compared to other biomarker tests.

When the MPS2 test is administered to men with high PSA levels, it lessens the incidence of false positives that result when relying on PSA alone. It more accurately determines the presence of clinically significant cancer than just a PSA test, which means using MPS2 can reduce the incidence of unnecessary prostate biopsies.

To be clinically validated, a test also needs to be “reproducible,” which means it will generate the same results in different patient populations. Also, the test should be analyzed by a facility not directly affiliated with the commercial manufacturer, and by researchers who have no financial stake in the test.

Sensitivity and specificity in testing

The “sensitivity” and “specificity” of a test are other important considerations in determining its clinical validity.

• A test has high sensitivity if it consistently detects the presence of disease, or has a high “true positive rate”: if a person has the disease, they will usually get a positive result on the test.
• A test has high specificity if it consistently gives a negative result when the disease is not present–the test has a high “true negative rate.”

For example, PSA tests are administered to detect the presence of prostate cancer. People with a low PSA level usually do not have prostate cancer, but people with a high PSA level might have prostate cancer, or they might have another condition, like BPH, that makes their PSA high. Therefore, a PSA test has high sensitivity and low specificity in detecting prostate cancer.

The MPS2 test was developed to detect the presence of high grade, or clinically significant, prostate cancer. MPS2 has high sensitivity for clinically significant prostate cancer, which means the majority of high grade prostate cancers are correctly identified by a positive result. Correspondingly, the MPS2 test has very few false negatives–that is, patients with clinically significant prostate cancer will seldom get a negative test result.

In addition to being highly sensitive, MPS2 also has a high “negative predictive value.” This means that there is a high likelihood that a person with a negative test result truly does not have the disease. Of the men who get a low MPS2 score, 93-99% would not have high-grade cancer.

Screening tests are often marketed directly to the consumer, so it is key that they have a credible scientific basis and correctly represent the risks and benefits of testing so consumers can make an informed decision on whether to use the test.

Clinical validation and peer-reviewed findings are important steps in scientifically demonstrating that a test is accurate, reliable, and reproducible, and that the research backing it up is valid and trustworthy. The peer-reviewed findings published on MPS2 in JAMA Oncology show that the test is clinically valid. Furthermore, the study shows how MPS2 outperforms other biomarker tests for prostate cancer and can identify up to half of the patients whose biopsy would be negative for clinically significant cancer, preventing unnecessary biopsy procedures.