BB&T Contributing Editor

WASHINGTON — Clinical diagnostics plays a key role in the healthcare system by providing the information upon which an estimated 70% of all medical decisions are based. The importance of its role is often underappreciated, since in vitro diagnostic testing accounts for less than 5% of overall healthcare spending. Recently, however, awareness of clinical diagnostics has increased due to the introduction of new genomic tests for assessing disease risk and for guiding cancer therapy, and that trend is likely to continue as diagnostic testing becomes more closely intertwined with therapy in the rubric of personalized medicine.

The 2008 annual meeting and clinical lab expo of the American Association for Clinical Chemistry (AACC; Washington), held here in late July, is the premier event for the clinical diagnostics industry, and often the venue for introduction of new products for the clinical lab, including products from vendors in all of the major geographic markets worldwide.

Major areas of focus at the 2008 AACC meeting included laboratory automation and integration of testing modalities, cancer diagnostics and pharmacogenomic testing, cardiovascular diagnostics, infectious disease testing, and point-of-care testing. In addition, a number of specialized niches of diagnostic testing were highlighted at the conference, including new tests for preeclampsia, cell and tissue diagnostics, tests for kidney injury, anemia diagnostics, and pre-natal testing.

The global market for clinical diagnostic products totaled over $37 billion in 2007, as shown in Table 1 on the next page. By 2012, the worldwide market is expected to exceed $52 billion. High-growth segments include molecular diagnostics, point-of-care testing including whole blood glucose self-testing, and certain other segments such as cell and tissue diagnostics. Leading suppliers in the market include Siemens Healthcare Diagnostics (Deerfield, Illinois), Roche Diagnostics (Indianapolis), Abbott Diagnostics (Abbott Park, Illinois), Beckman Coulter (Brea, California), BD (Franklin Lakes, New Jersey), Ortho Clinical Diagnostics (Raritan, New Jersey), bioMerieux (Marcy L'Etoile, France) and Bio-Rad Laboratories (Hercules, California).

One driver of growth in the diagnostics market is the expanding role of in vitro diagnostic testing in therapy guidance. In vitro diagnostic testing is being employed increasingly in the guidance of drug therapy, for example, as pharmaceutical companies introduce new targeted drugs that rely on use of a diagnostic assay to verify presence of the biological target in order to qualify a patient for treatment.

Roche, also a major pharmaceutical supplier in addition to a leading diagnostics supplier, is developing companion tests along with all its new cancer drugs, and almost all development of new proprietary pharmaceuticals is focusing on biologically targeted drugs. So far, there are a limited number of pharmacogenomic tests in common use, but the segment is expected to expand considerably as more targeted drugs are introduced.

Another area of healthcare in which the role of diagnostics is expanding is infectious disease management. That area is becoming increasingly important as hospitals implement measures to reduce hospital-acquired infections, particularly those involving drug-resistant organisms such as methicilin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant staph aureus (VRSA), as well as HIV.

Many hospitals now screen all newly admitted patients in the ICU for MRSA, and new guidelines published by the Centers for Disease Control and Prevention (Atlanta) in 2006 now recommend routine opt-out HIV screening for all patients between the ages of 13 and 64 in acute-care hospitals. Opt-out provides patients with the opportunity to ask questions prior to being tested and the option to decline testing. In hospitals that have implemented rapid HIV screening of emergency department patients, HIV test volume has increased as much as 5-fold, driving demand for new diagnostic testing systems in hospital laboratories.

The role of diagnostic testing also is expanding outside of the traditional hospital and reference laboratory setting, driven in part by efforts to limit the spread of infectious diseases in developing countries worldwide. As discussed by Mark Perkins, PhD, of the Foundation for Innovative New Diagnostics (FIND; Cointrin, Switzerland) at an AACC plenary session on diagnostics for disease control in developing countries, only 10% of the inhabitants of low- and middle-income countries have ever been tested for HIV infection, and only one-fourth of individuals with tuberculosis infections have been tested for TB. Rates of diagnosis for malaria, which has one of the highest incidence rates of any disease worldwide with more than 400 million new cases annually, according to the latest statistics from the World Health Organization (Geneva, Switzerland), are only 15%.

New point-of-care testing and rapid molecular diagnostic technologies are being employed to expand diagnostic testing for infectious diseases such as HIV, mTB, and malaria in less developed countries. Perkins described a molecular assay from Hain Lifescience (Nehren, Germany) for multidrug-resistant tuberculosis that reduces turnaround time from two to three months to two days or less, and a new TB test developed jointly by FIND and Eiken Chemical (Tokyo) that uses a closed-tube LAMP assay format with visual read-out and sensitivity equivalent to culture, making it suitable for use in developing countries.

Cancer diagnostics and pharmacogenomics

New developments in cancer testing were another major topic at the AACC conference, including developments in tests for guiding treatment with biologically targeted anti-cancer agents (pharmacogenomic tests) as well as new tests for monitoring treatment with conventional chemotherapy drugs. Saladax Biomedical (Bethlehem, Pennsylvania) described the development status of its Personalized Chemotherapy Management (PCM) tests for monitoring of blood levels of common chemotherapeutic drugs.

The company's initial product is a test for measurement of levels of 5-fluorouracil in the blood. 5-FU is widely used in the treatment of colorectal cancer. More than 1 million new cases of colorectal cancer are diagnosed annually worldwide, and chemotherapy is used to treat most colorectal cancer patients who have metastatic disease. Blood levels of 5-FU must be maintained within a narrow range to avoid toxicity and maintain effectiveness. However, a study by Gamelin et al., published in the May issue of the Journal of Clinical Oncology, found that only 25% of patients receiving 5-FU are maintained in the target range when dosing is performed using body surface area as the metric for establishing dose. 17% were over-dosed and 58% were under-dosed.

In contrast, use of the Saladax 5-FU test to monitor dose level and maintain it within the target range resulted in a doubling of response rate and improved survival, with lower rates of toxicity. The company has just launched the test in Europe, where it can be performed on the AU400 analyzer from Olympus (Tokyo), having a throughput of up to 400 tests per hour and a turnaround time of a few minutes.

Existing test methods for 5-FU, primarily employing liquid chromatography/mass spectrometry, have a considerably lower throughput and longer turnaround time, and require specialized equipment and highly trained operators. The Saladax 5-FU assay will not be introduced as an FDA-cleared test kit in the U.S., but will instead be offered as a reference lab test through a partnership between Saladax and a U.S. reference laboratory beginning in 2009.

Saladax also is developing a test for monitoring of blood levels of bisulfan, a drug used in cell transplant therapy for cancer. The bisulfan test will be submitted for 510(k) clearance in the U.S., allowing it to be performed in U.S. hospital labs.

Roche Diagnostics, the leading company in the in vitro diagnostics market, including blood glucose self-testing, is aggressively pursuing development of pharmacogenomic tests for use in guiding cancer therapy. Roche recently established a partnership with DxS Ltd. (Manchester, UK) for distribution of the Therascreen:K-RAS and Therascreen:EGFR 29 assays.

Therascreen:K-RAS is a molecular genotyping test used to select patients with metastatic colorectal cancer for treatment with Erbitux, a drug from ImClone Systems (New York) that targets the epidermal growth factor receptor (EGFR), or Vectibix, a targeted drug from Amgen (Thousand Oaks, California). The test is a real-time PCR assay that detects seven specific mutations in the k-ras oncogene which are associated with response to therapy.

The Therascreen:EGFR 29 test detects the 29 most common mutations in the EGFR gene associated with response to targeted tyrosine kinase inhibitor therapy using drugs such as Iressa from AstraZeneca (London) and Tarceva from Genentech (South San Francisco, California)/OSI Pharmaceuticals (Melville, New York) used in the treatment of non-small cell lung cancer and pancreatic cancer. Tyrosine kinase inhibitors are also being studied for use in treating other cancers including breast cancer.

Cancer-related pharmacogenomic tests under development by Roche Diagnostics include BRAF V600E, a test that will run on the AmpliCor platform to select patients with malignant melanoma for treatment with PLX4032, a drug co-developed by Roche Pharmaceuticals and Plexxikon (Berkeley, California); and a p53 oncogene test that will run on the Roche AmpliChip platform to select breast cancer patients for treatment with Nutlins, which are small molecule MDM2-p53 antagonists.

Roche believes that its position as the leading diagnostics company, including its leadership in the molecular diagnostics market, combined with its position in the pharmaceutical market provides a significant competitive advantage, both for its diagnostics and pharmaceutical businesses. The company is pursuing a strategy based on its conviction that personalized medicine, which is enabled by pharmacogenomic testing and targeted therapies, is here to stay, and will increasingly be the way in which patients are managed.

New tumor marker tests described at the AACC meeting are expected to drive expansion of the cancer diagnostics market. Beckman Coulter described preliminary results with a new prostate cancer marker, pro-PSA or P2PSA, which is intended for use along with the company's existing free and total PSA tests to improve the specificity of cancer detection. At present, only one in five positive total PSA tests is confirmed by biopsy. The new pro-PSA test is designed to provide better discrimination between men with prostate cancer and those with benign conditions of the prostate.

Gen-Probe (San Diego) has entered the prostate cancer diagnostics market outside the U.S. with its Progensa PCA3 gene-based urine test for prostate cancer. The PCA3 assay uses the company's transcription-mediated amplification (TMA) to quantify PCA3 mRNA in urine, generating a score that can be used in combination with other parameters to more accurately predict biopsy outcomes.

Abbott Diagnostics, historically a leader in the tumor marker segment and also one of the few companies with a true pharmacogenomic test on the market (the Vysis PathVysion HER2 FISH test), is collaborating with Genentech, Roche and OSI Pharmaceuticals to develop a molecular in situ hybridization assay for prediction of response to Tarceva in non-small cell lung cancer patients.

An emerging player in the cancer diagnostics market, Vermillion (Fremont, California), formerly Ciphergen Biosystems, is developing a new tumor marker panel for ovarian cancer, the OVA1 Ovarian Tumor Triage Test. Vermillion filed a 510(k) application for marketing clearance of the OVA1 test in June. The test is intended for risk assessment in patients diagnosed with ovarian cancer, enabling separation of patients into high- and low-risk groups to help determine if the patient should be referred to a gynecologic oncologist prior to surgery.

There has been a considerable level of activity in the area of ovarian cancer tests recently, including the introduction of the OvaSure reference lab test by LabCorp (Burlington, North Carolina), a serum proteomic test that uses a panel of six biomarkers for early detection of ovarian cancer, launched in June. The OvaSure markers include leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, and CA125. The test was developed using the multiplex immunoassay technology from Luminex (Austin, Texas), to screen a larger panel of markers along with an analytical algorithm to identify the optimal test panel.

Another new ovarian cancer marker, HE4, is under development by Fujirebio Diagnostics (Malvern, Pennsylvania). The HE4 marker can be combined with CA125 to provide improved sensitivity for early detection of ovarian cancer, with a sensitivity of 76.4% and specificity of 95% reported in a study conducted by Richard Moore, MD, at Brown University (Providence, Rhode Island).

As discussed by Robert Bast, MD, at an AACC symposium on cancer management, the optimal approach to ovarian cancer detection combines serum marker analysis with ultrasound imaging, with a goal of increasing the proportion of patients who are diagnosed when the disease is at an early stage. When diagnosed at Stage 1, cure rates for ovarian cancer are 90%, according to Bast, whereas the cure rate drops to 20% if the cancer already has spread at initial diagnosis. Using existing test methods (CA125 combined with ultrasound imaging), only 25% of ovarian cancers are diagnosed at Stage 1.

Tissue diagnostics in rapid growth

Another rapidly growing segment of the cancer diagnostics market is tissue diagnostics. Tissue diagnostics involves analysis of biopsy materials and other tissue specimens using immunohistochemistry, histochemistry, in situ hybridization and cytology to detect cancer or infectious diseases. The segment was quite small and slow-growing until the mid-1980s, when new high-value tests such as those for detection of human papilloma virus in PAP specimens were introduced, followed by the introduction of new tests for cancer markers such as HER2 and automated systems for tissue analysis from companies such as Ventana Medical Systems (Tucson, Arizona), now a unit of Roche Diagnostics.

As shown in Table 2, the market has expanded to become a significant segment of the total in vitro diagnostics market, reaching $1.3 billion worldwide in 2007 excluding research applications. In addition to the adoption of higher-value tests such as molecular assays and automation, the market is being driven by the growing incidence of cancer worldwide, which has reached roughly 9.3 million cases annually according to the most recent (2002) data from the World Health Organization. Shortages of skilled technicians to perform tissue testing are driving labs to adopt automation, both in the U.S. and more recently in Europe.

Key players in the automated tissue diagnostics market include Roche Diagnostics, via its acquisition of Ventana; Dako A/S (Glostrup, Denmark); Abbott Diagnostics' Vysis unit (Abbott Park, Illinois) and Leica Microsystems (Wetzlar, Germany). In addition, companies including Olympus sell automated microscopy systems that are used in tissue diagnostics, and Cytyc, a unit of Hologic (Bedford, Massachusetts) supplies products for automation of cytology testing.

Roche claims the leading position in the advanced staining segment of the tissue diagnostics market, with sales of between $250 million to $300 million in 2007, growing at 32% annually based on first-half 2008 revenue (27% in Swiss francs). In the second half of 2008, Roche will launch the BenchMark Ultra, a continuous access IHC/ISH staining system that provides walk-away automation at a throughput of 90+ slides in one 8 hour shift and LIS connectivity. Roche introduced the Vantage workflow management software, which provides sample tracking and other data management features, in the first half of 2008. Three Vantage systems had been installed in the U.S. as of the time of the AACC meeting. Pathology labs also are moving to digital imaging and electronic storage of pathology images, enabling quantitation of markers in tissue specimens, telepathology and elimination of retrieval of slides for image review.

For example, a new system recently introduced by Olympus, BLISS HD, provides high-definition virtual microscopy capabilities for pathology labs, automatically scanning a slide and storing images which can then be reviewed on a computer screen. The user can perform essentially any manipulation of the images that can be performed with a conventional microscope, but images can be accessed much more quickly and annotation and sharing of images is significantly simplified. The BLISS HD joins the existing NanoZoomer multi-slide scanning system from Olympus, which enables unattended scanning of up to 210 slides, allowing pathology labs to have slides prepared during the day to be automatically scanned overnight.

A new entrant in the tissue diagnostics market, HistoRx (New Haven, Connecticut), exhibited its Aquantiplex assays and Aqua image analysis technology at the conference. The products are designed for performing automated immunohistochemistry analysis, and employ fluorescent labels along with antibody reagents for quantification of biomarker expression in epithelial tissue samples. The company's initial product for the clinical diagnostics market is a test for quantification of estrogen receptor in breast biopsy specimens; a 510(k) application for that product was submitted at the end of June.

HistoRx also is developing a HER2 assay for the clinical market, and plans to internally develop or license a number of other tissue marker assays, including pharmacogenomic tests developed with pharmaceutical company partners. The HistoRx assays can be used on automated slide strainers such as those from Roche Tissue Diagnostics. The company currently sells products for research use, including the PM-2000 image analysis system and Aqua tissue an-alysis software, and provides tissue-testing services to pharmaceutical companies and resear-chers.

Automation, platform integration advances

A number of new automated systems for the central lab were introduced at the meeting. The number of labs adopting automation has expanded steadily over the past few years, driven by chronic shortages of lab technologists and increasing test volume coupled with restrictions on budgets and hiring of new staff. Automation in the central laboratory is proceeding along two fronts. First, larger labs are adopting track-based specimen handling and routing systems that automate transfer of specimens between different analyzers and also archive specimens so that they can be automatically retrieved for re-testing or reflex testing.

The number of labs that have adopted track-based automation (total lab automation) in the U.S. increased more than three-fold between 2002 and 2006, and is estimated at about 5% of all central labs in the U.S. as of early 2007. Examples of lab automation systems include the Automate 800 and the newly launched Automate 600 track-based automation systems from Beckman Coulter, the Flex-Trak automation system from Olympus, the Streamlab system from Siemens Medical Diagnostics, the Accelerator lab automation system from Abbott Diagnostics, and the Total Lab Automation (TLA) and Task-Targeted Automation (TTA) systems from Roche Diagnostics.

Lab automation systems coupled with advanced laboratory informatics enable adoption of the growing paradigm of lean labs, allowing increased test volume and throughput with the same or reduced staffing levels. That paradigm is being adopted by clinical laboratories worldwide, since all are facing the same pressures including cost containment, increased workload, and labor force issues.

A key advantage of total lab automation is the simplification of testing procedures. For example, implementation of the Beckman Coulter Automate system in one large lab performing 2,500 tests per day in Canada resulted in a reduction in processing steps from 25,800 to 8,310. Automated sample-handling systems also typically incorporate features that improve the quality of lab results, such as automated assessment of samples for hemolysis, and reduce lab errors by reducing processing steps and data transcription errors. According to Beckman Coulter, automated labs are catching up to 70 times more hemolysis in incoming specimens than with manual quality checks.

A second front of lab automation is integrated workcells, including systems that perform tests such as chemistry and immunoassay on a single platform. One of the newest entrants in that segment is Ortho Clinical Diagnostics with the Vitros 5600, which is now in beta testing in the U.S. and will be launched in 4Q08. The new system was demonstrated for the press at a site visit to the main lab at George Washington University Hospital (Washington), one of seven beta sites for the Vitros 5600.

The system combines four technologies in a single platform, including Vitros dry slide chemistry, the OCD microsensor technology for electrolytes, the microtip technology first introduced in the Vitros 5.1 analyzer, and microwell immunoassay technology from the Vitros ECi system. The 5600 provides pre-analytical test sequencing, automatically arranging the order in which tests are performed to provide reliable turnaround time even though actual test times for the various chemistry and immunochemistry tests vary from two to 70 minutes. The system eliminates on-board aliquotting via its modular design, and eliminates the risk of carryover.

The George Washington University Hospital lab expects to realize significant cost savings by performing tests in-house with the expanded menu available on the 5600. For example, a test costing $25 when performed by an external lab may cost $5 when performed internally. Tests that have already been brought into the lab include Hepatitis A Total Antibody, Hepatitis A IgM Antibody, Hepatitis B Surface Antigen, Hepatitis B Surface Antigen Confirmatory, Hepatitis B Surface Antibody, Hepatitis B Core IgM Antibody, Hepatitis B Core Total Antibody, Hepatitis C Antibody, homocysteine, high-sensitivity CRP, NT pro-BNP, Vitamin B12 and serum folate. The lab also plans to bring in-house HIV-1/2 antibody testing, and expects to realize cost savings of more than $30,000 per year. The George Washington University Hospital lab has been able to increase total test volume by 25% over three years while keeping FTEs constant as a result of consolidation of analyzers, eliminating five analyzers and transferring those tests to the OCD platforms while adding tests that were previously sent out. Further instrument consolidation is possible and there is also potential to bring more tests in-house if the Vitros 5600 is adopted.

Beckman Coulter offers an integrated workcell for chemistry/immunochemistry testing, combining its DxI 800 immunochemistry analyzer with a throughput of 400 tests per hour with the DxC 800 chemistry analyzer to create the UniCel DxC 880i high-volume work cell. A key feature of the DxC 880i is closed-tube sampling and aliquotting, which helps minimize biohazard exposure in the lab. The system also reduces processing steps from 17 for specimens run manually on separate analyzers to two for the DxC 880i.

The company next will introduce the DxC 660i integrated chemistry and immunochemistry system, pending FDA clearance. The DxC 660i combines the DxI 600 immunochemistry analyzer with the DxC 600 chemistry analyzer, and is targeted at mid-volume labs. Additional models to be launched in the future will combine a mid-volume immunochemistry analyzer with a high-volume chemistry system (e.g., the DxI 600 and the DxC 800) and vice-versa, enabling labs to have a high degree of flexibility for meeting their test volume requirements.

Siemens Medical Diagnostics, the leading supplier of integrated chemistry/immunochemistry systems with the Dimension family, exhibited the new Dimension ExL system, which includes an integrated immunoassay module that uses the LOCI technology for high-sensitivity chemiluminescence immuno-assay testing. Siemens recently received 510(k) clearance for the ExL LOCI module, which will enable shorter test turnaround times and higher sensitivity compared to previous Dimension immunoassays.

According to Siemens, 81% of U.S. hospital labs which have an integrated chemistry/immunochemistry system use a Dimension analyzer. Based on data from Information Dynamics, Siemens estimates that the percentage of U.S. labs with integrated chemistry/immunochemistry analyzers increased from 19% in 2001 to 53% in 2007.

New applications drive growth

A number of new applications for clinical diagnostics were described at the AACC conference involving immunoassay and molecular diagnostic testing that are expected to expand the market in the future, including preeclampsia diagnosis, detection of kidney injury, advanced anemia diagnosis, and new approaches in pre-natal testing. Preeclampsia diagnostics address a significant healthcare need that is unmet by existing IVD testing, since so far no biomarker has been commercialized that is capable of detecting the syndrome. At present, diagnostic methods include blood pressure monitoring, urinary protein measurements, ultrasound imaging, and clinical symptoms. The only treatment for preeclampsia is delivery of the placenta, so accurate diagnosis is critical.

A viable blood or serum marker would address a large market opportunity, as indicated in Table 3. If only 10% of pregnancies are identified as at high-risk for preeclampsia and testing is performed at $15 per test, the annual market would be $300 million worldwide. Roche Diagnostics is developing two new biomarker tests for preeclampsia, PlGF and sFlt-1, while Beckman Coulter is evaluating placental growth factor and sVEGF R1, two markers discovered at the National Institutes of Health and Beth Israel Medical Center (New York).

Molecular markers may also prove to be important for preeclampsia diagnosis. Dennis Lo, of the Prince of Wales Hospital (Hong Kong), is studying the measurement of circulating fetal mRNA in maternal blood as a non-invasive method for pre-natal diagnosis, and has identified four mRNA markers that may prove useful in preeclampsia, including corticotropin-releasing hormone, VEGF, and VEGF R-1. In addition, as described at an AACC symposium on prenatal diagnosis using cell-free nucleic acids in maternal blood, he is investigating microRNA markers for preeclampsia, including miR210 and miR182. The use of circulating fetal DNA and RNA in maternal blood as a non-invasive approach for pre-natal diagnosis is an expanding area of clinical research, with applications in diagnosis of a number of diseases in addition to preeclampsia.

Lo also is investigating circulating DNA assays for pre-natal diagnosis of Down's syndrome that employ microfluidic arrays from Fluidigm (South San Francisco, California) for sample processing and nucleic acid amplification, along with microarrays from Affymetrix (Santa Clara, California) for detection and analysis. For microRNA analysis, a limitation is the need for a minimum of 3,000 molecules in the primary sample in order to obtain an accurate result. Lo is using the BioMark Digital Array microfluidic chip from Fluidigm to perform digital PCR as a means to increase sensitivity and reduce the number of molecules required for analysis.

Other researchers are investigating circulating fetal DNA and RNA markers for additional genetic disorders such as congenital adrenal hyperplasia, and applications of circulating nucleic acid analysis in cancer diagnostics also are under development.

A new marker for acute kidney injury, urine neutrophil gelatinase-associated lipocalin (NGAL), is being developed by Abbott Diagnostics. Acute kidney injury or AKI, previously known as acute renal failure, is a significant healthcare problem, affecting 30% to 50% of patients in intensive care units, and the incidence rate appears to be increasing rapidly. There is presently no effective marker for AKI. Creatinine levels have traditionally been used to monitor renal function, but creatinine is not a reliable marker for AKI, as it does not become elevated until 48 hours after the onset of injury. In addition, kidney function can deteriorate by as much as 50% without any elevation in creatinine.

Although some potentially effective treatments to prevent AKI have been identified based on an improved understanding of the underlying mechanisms of injury, the lack of an early marker of AKI has hindered development of those therapies. An early AKI marker also would be a necessary prerequisite for using any new treatments in the clinical setting. Abbott has developed a urine NGAL assay for its Architect immunoassay platform that has good performance in detecting AKI at an early stage.

A pilot study of AKI in cardiac surgery patients conducted by Bennett, et al., at the University of Cincinnati School of Medicine, published in the May issue of the Clinical Journal of the American Society of Nephrology, found that urinary NGAL levels as measured with the Architect assay at two hours post-coronary bypass surgery was highly predictive of the severity and duration of AKI, length of stay, need for dialysis and death. Urinary IL-18 and KIM-1 are additional markers that may complement NGAL for the detection of AKI. Abbott plans to launch the Architect NGAL assay in Europe in 2009, and is targeting a U.S. launch in 2010.

Anemia diagnostics is another area of new marker development. Beckman Coulter is developing Soluble Transferrin Receptor as a diagnostic marker to help differentiate iron deficiency anemia from anemia of chronic disease, the two most common types of anemia. The diagnosis is important, since treatment methods for the two conditions are very different.

Existing anemia markers such as MCV (mean corpuscular volume) as determined via hematology analysis, serum iron, and transferrin are not reliable for differentiation of the two types of anemia, leading to a need for a new, more effective marker. Soluble transferrin receptor (sTFR), first discovered by researchers in Finland in the mid-1990s and now available as an immunoassay from Beckman Coulter in Europe and Canada, has been shown to be a good discriminator of iron-deficiency anemia vs. anemia of chronic disease, and is now undergoing FDA review.