An Old Diagnostic Gets the Boot: PSA Testing in Healthy Men is No Longer Recommended

This week, the United States Preventive Services Task Force is due to release its draft recommendation on the use of the Prostate-Specific Antigen (PSA) test in healthy men of all ages.  The PSA test has been a standard tool in urology to assist in the diagnosis of prostate cancer.

Essentially, this recommendation states that the PSA test in healthy men has no clinical benefit, does not save lives, and actually may lead to unnecessary follow up tests and procedures that can have deleterious effects on the patient’s health (see The New York Times article).

These conclusions are based on the results of five well-controlled clinical studies which confirm the general empirical consensus about the PSA test: its lack of specificity and sensitivity result in unacceptable numbers of false positive and false negative tests, respectively.  In particular, false positive tests are particularly troublesome since a positive test will usually lead to a biopsy and treatment that can lead to impotence and/or incontinence.  While those risks of complications are somewhat acceptable for actual prostate cancer patients, they are unacceptable for individual who have misdiagnosed.

This recommendation by the United States Preventive Services Task Force is already producing strong reactions from prostate cancer survivors and advocacy groups.  The idea of shelving the PSA test is unacceptable to those who feel that this diagnostic saved their live.  The truth is that neither the PSA test nor other currently available tests are particularly useful in detecting prostate cancer.  Hence, there is an urgent need to develop, clinically validate, and deploy effective tools for the early detection of prostate cancer in apparently healthy men.  Ironically, the dominance of the PSA test on the market has probably a substantial obstacle to the development of new diagnostic in this field.  Indeed, the protectionism from a segment of the diagnostic industry with financial interest in PSA testing, as well as the difficulty to change medical practices among physicians have probably contributed to the lack of alternative prostate cancer diagnostics.  One can speculate that the new recommendation about PSA testing will open a breach for innovative tools that will actually save lives.


Thierry Sornasse for Integrated Biomarker Strategy

The Forces Driving the Future of Personalized Medicine

Transport yourself 10 to 15 years from now and try to imagine what the future of personalized medicine will look like.  The vision of every drug prescription decisions being driven by a test aimed at tailoring the treatment to a particular individual is probably utopian.  Rather, I would argue that the realm of personalized medicine will still be limited to the treatment of severe and/or life-threatening diseases that require expensive medications.  Under this premise, what are the forces that will shape the future of personalized medicine?

In my mind, this question can be addressed by considering the field from a supply and demand perspective.  On the supply end, the pharmaceutical and diagnostics industries will remain the main forces driving the future of personalized medicine.  The imperative of improving the return on investment in drug development will dominate the future of the pharmaceutical industry.  With the era of relying mainly on “one-size-fit-all” drugs fading away, the focus will shift towards precision/personalized medicine where drugs are designed to address the need of smaller targeted patient populations.  Hence, the need to develop the tools that will identify the right patient population (for efficacy and/or safety reasons) will constitute a major theme in drug development.  This does not exclude the continuing effort of the pharmaceutical industry to develop and commercialize broadly applicable drugs for the management and/or treatment of conditions for which a personalized approach is not warranted (for cost-benefit and/or clinical utility reasons).  Still on the supply end but with an eye on the demand side, the regulatory authorities will continue to play a major role in the harmonization of the biomarker and companion diagnostic development process.  Beyond the current regulatory framework governing the regulatory approval of drugs and companion diagnostics, the regulators have been working on developing a new process for an integrated development of biomarkers intended to become companion diagnostics (see earlier posts: Harmonization of Biomarker Qualification Regulatory Submissions; Companion In Vitro Diagnostics (IVD) Development).

Probably the most significant force that will shape the future of personalized medicine will be on the demand side, represented by the patients, the medical practitioners, and most importantly the health insurance/payers.  For all three entities, the adoption of a new companion diagnostic will require proof of clinical utility (Ref1, Ref2, & Ref3).  In a nutshell, clinical utility for a molecular diagnostics is the third level of a three-tiered evaluation framework that includes “analytical validity”, “clinical validity/qualification”, and “clinical utility” (Ref2).  Hence, clinical utility encompasses the overall medical impact of a diagnostic.  A diagnostic is considered clinically useful if it provides a real and substantial advantage to the patients, positively alters the practice of medicine, and/or improves the cost / benefit equation for a given treatment.  Although clinical utility is a distinct concept from analytical and clinical validity, it cannot be established without first establishing the latter.  The reciprocal is however not true: establishing analytical and clinical validity does not imply proof of clinical utility.

While the pharmaceutical industry and the regulators are currently focusing most of their efforts on defining and implementing the rules of diagnostics analytical and clinical validation, I would argue that the next decade will be dedicated to the third part of the equation: defining and implementing the rules of diagnostics clinical utility evaluation.

Thierry Sornasse for Integrated Biomarker Strategy