Patient Safety and Diagnostic Accuracy | How a Simple DNA Test Can Assure Your Accurate Diagnosis
By Peter Knapp, MD
When your doctor gives you the results of your biopsy and tells you that you have cancer, many questions race through your mind. “Are you sure? How could I have cancer when I feel fine? Could this be a mistake?”
Hundreds of thousands of patients go through this emotional trauma each year, as over one million patients in the United States are diagnosed with cancer including prostate, breast, lung, and other solid organ cancers. For most patients the diagnosis is accurate, but an alarming 2.5% of patients are at risk of being given the wrong diagnosis as a result of a biopsy mix-up with another patient, and may proceed unknowingly toward unnecessary treatment with significant risks and side effects.
Medical Mistakes
Medical mistakes have been reported in the news for many years. The Wall Street Journal reported in August 2014 that diagnostic errors occurred 5% of the time, affecting 12 million people per year. In 2017, the New York Times reported a case of a prostate biopsy specimen switch resulting in the wrong patient being given the diagnosis of cancer while the patient with cancer was told he was cancer free.
Studies have shown that biopsy specimen switches and contaminations called Specimen Provenance Complications (SPCs) can occur in the biopsy collection room or any one of several steps in the diagnostic testing cycle in the laboratory. Eighteen steps can be identified in the diagnostic testing cycle from the time the biopsy specimen is obtained and labeled to the time the result is reported to the treating physician. Many steps involve human handling of the biopsy specimen and can result in unexpected and inadvertent specimen switches or contamination. Specimen switches, unknown to the treating physician or patient, can result in patients being given someone else’s diagnosis. Specimen contaminants can result in biopsy tissue specimens from different patients being examined on a single laboratory slide. The contaminated slide is often unrecognized by the examining pathologist and potentially results in assigning the wrong diagnosis to a patient. Unrecognized or occult specimen switches and contaminations can result in unnecessary treatment of one patient while another patient’s proper diagnosis may be delayed, allowing their disease to progress.
The American Journal of Clinical Pathology published a study from Washington University in 2013, which reported a biopsy switching or contamination rate ranging from 0.8 percent to 3.5% in patients with prostate cancer, posing a serious threat to patient safety.1 The Washington University study documented the rate of occult SPC occurrence through a prospective analysis of approximately 13,000 prostate biopsies performed as a part of routine clinical practice. Results found that up to 3.5% of specimens being evaluated may not come from the patient being diagnosed. Since each case involves at least two individuals, this error rate actually underestimates the percentage of patients potentially affected by incidents of biopsy misidentification.
Fortunately, today, diagnostic errors due to specimen switches and resultant medical treatment mistakes can be eliminated with a simple DNA test to confirm the biopsy tissue being examined by your doctor belongs to you. DNA Specimen Provenance Assay (DSPA) is a test using a DNA analysis to match a biopsy tissue sample to a DNA reference sample from the same patient before a diagnosis is given and treatment rendered. DSPA testing can be routinely performed using the Know Error biopsy kit. The Know Error biopsy kit was developed by doctors to precisely collect and identify biopsy tissue specimens to verify origin of the biopsy sample.
DNA Specimen Provenance Assay (DSPA) testing is performed in the DNA laboratory, matching DNA from the cheek swab to the tissue specimen read as cancer by the pathologist.
Once the biopsy specimen has been accurately matched to the cheek swab reference sample, the diagnosis is confirmed as accurate and reported to the doctor before any treatment can be rendered.
Confirming the DNA match between a patient’s cheek swab sample and their biopsy tissue completes the diagnostic testing cycle, ensures diagnostic accuracy, and prevents medical treatment errors due to misdiagnosis.
In the Washington University study, all biopsies were performed using the Know Error biopsy system and included specimens from over 50 different laboratories. DSPA testing was performed for all patients with a positive cancer diagnosis. Results showed that the average SPC rate was 0.93% with a 0.26% specimen switch rate and 0.67% specimen contamination rate. The SPC rate in some laboratories was as high as 3.5%, with the specimen switching rate as high as 0.37%. SPCs were found in all laboratory and practice settings, indicating that despite state-of-the-art specimen collection and recording measures, including (1) specimen barcoding, (2) rigorous chain of custody, and (3) detailed specimen handling protocols, occult errors occur and no laboratory or practice is immune to this problem.
The results from a large, international clinical trial reviewing prostate biopsy specimens estimated that SPC’s can be expected to lead to misdiagnosis and significant patient harm in at least 0.57% of all prostate biopsies, or 1.13 in every 200 patients. Among an estimated 806,251 primary and secondary prostate biopsies performed annually in the United States, 20,322 (2.52%) are projected to involve SPCs, resulting in 4,570 (0.57%) clinically meaningful false diagnoses.
Precision Medicine
Today’s promise of precision medicine and targeted therapy requires complete diagnostic accuracy and the elimination of diagnostic errors due to specimen switches and contaminations. Medical mistakes due to diagnostic errors resulting from specimen switches and contamination can be completely eliminated with the routine use of DSPA testing to complete the diagnostic testing cycle and ensure diagnostic accuracy. Implementation of routine DSPA testing will require increased patient awareness, medical community implementation, and Medicare and other payer insistence that DSPA testing be utilized to provide patient safety, diagnostic accuracy, and cost savings to the healthcare system.
Ask your doctor about DSPA testing and the Know Error biopsy kit.
Pfeifer JD, Liu J. Rate of occult specimen provenance complications and routine clinical practice. Am J Clin Path. 2013;139 (1):93-100
Marberger et.al. J Clin Onc Vol.29: Number 13, May 2011
Wojno et.al. The clinical and economic implications of specimen provenance complications in diagnostic prostate biopsies, JUrol Vol.193, 1170-1177, April 2015
Milliman report 2016 prepared for the Congressional Budget Office
About Dr. Knapp
Peter M. Knapp, MD, FACS is Co-Founder and Director of Strand Diagnostics LLC, and co-developer of the Know Error DNA Specimen Provenance Assignment (DSPA) test and kit used to improve diagnostic accuracy and patient safety in the evaluation of patient tissue specimens. Dr. Knapp is a practicing urologist involved in medical education, clinical research, product development, practice growth and clinical service line expansion for over 25 years. He holds multiple healthcare patents, has authored more than 30 articles and several book chapters, and served as principal investigator or sub-investigator on more than 50 clinical trials. He is certified by the American Board of Urology and is a fellow of the American College of Surgeons.