THE AUTHORITATIVE SOURCE FOR THE C PCAPABILITIES …€¦ · ration around thyroid test ordering...

PHYSICIAN HEALTH ITCAPABILITIES NOT MEETINGCONSUMER DEMANDDespite high consumer demand for online access to health information and communication tools, provid-ers lag in their health IT capabilities, according to the Optum Institute’s new “Meaningful Consumer Engagement” report. The report summarized results of an online survey that included more than 4,000 physicians, hospital execu-tives, and adult healthcare consumers.

The survey found that three-quarters of patients want to view their medical records and lab test results online, but that only 41% of physicians have electronic medical record (EMR) systems that support timely access to this information. Likewise, more than 60% of patients want to correspond with their doctors via the Internet,

while only 44% of physicians have this capability. Consumers both young and old expressed their interest in engag-ing via health IT. For instance, 57% of consumers over age 65 expressed interest in online correspondence with healthcare providers, a number that is only slightly lower than the general population.

In spite of the lag in online physician-patient connections, Optum’s survey did find a positive trend in physician adoption of EMR, with 70% of healthcare providers having EMR systems capable of basic functions such as recording diagnoses and patient demographics. Over half of physicians also have EMRs that support basic care coordination; for instance, 60% can access patients’ clini-cal lab and test results online.

Stage 2 of the Center for Medicare and Medicaid Services’ Meaningful Use Program (MU2) aims to improve the sharing of such information with patients by giving physicians incentive payments to expand their IT capabili-ties. However, MU2 only requires 50% of patients to have access to their electronic health records, and 5% to use online tools. Since the number of consumers that want these capabili-ties is much higher, Optum believes MU2 has set the bar too low to meet consumer demand.

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Thyroid Health in PregnancyIs it Time to Implement Universal TSH Screening?BY GENNA ROLLINS

Pregnancy places unique demands on the thyroid gland and thyroid function, and has been called a stress test for this master regulator of metabolism. As many as 5% of pregnant women experience some sort of thy-roid dysfunction, putting themselves and their babies

at risk for short- and long-term health complications. Yet these common, potentially serious thyroid imbalances often are under-appreciated and may go undetected. Now, two new guidelines not only are raising the visibility of thyroid disease in pregnancy and calling attention to issues in need of further research, but also un-derscoring the importance of close laboratorian-clinician collabo-ration around thyroid test ordering and interpretation.

“I don’t think thyroid disorders get the attention they deserve in terms of research, publications, and awareness. One of the best things about these guidelines is they make frontline physicians think about thyroid health in pregnancy, because in terms of get-ting attention it’s way down the list. We’re always worried about preeclampsia, preterm birth, growth restriction, obesity, and dia-betes, so thyroid disorders tend to fall off the radar screen,” explained Scott Sullivan, MD. “Any information labs can provide that guides doctors in knowing which tests to order and how to interpret pregnancy-specific reference ranges would be helpful.” Sullivan, an associate professor of obstetrics and gynecology at the Medi-cal University of South Carolina in Charleston, served on committees for the American Thyroid Association (ATA) and the Endocrine Society, both of which recently issued guidelines on diagnosing and managing thy-roid dysfunction in pregnancy (Thyroid 2011; 21:1081–125; J Clin Endocrinol Metab 2012;97: 2543–65).

The Surge in Retail ClinicsExpansion of Services Signals More TestingBY BILL MALONE

As the healthcare system prepares to cope with an influx of 30 million Americans who will have health coverage as a result of the Affordable Care Act, a surging market of retail clinics is poised to take on a wider role to relieve the bottleneck. No longer merely an anomaly or an experiment of a few drug store chains, retail clinics have steadily expanded. While most only have a corner of real estate inside their host retailer, these quick-service healthcare establishments are widen-

ing the scope of care they provide. Over the last few years, many have added more advanced services and tests, partnering with health systems and insurers to become embedded in local healthcare ecosystems.

According to experts, quick-access clinics can be one part of the solution to improving access to basic health-care. Some insurers and healthcare systems already have retail clinics in mind for more than just minor, acute care visits, according to Tom Charland, chief executive of the research and consulting firm Merchant Medicine, which tracks the retail medicine market. “Insurance companies are now recognizing that pharmacies and retail

clinics can do chronic disease management pretty efficiently. We are in the early stages of this area, but the scope is definitely changing,” he said.

Not only do insurers see retail clinics as facilitators of disease management, but also as a stop gap measure for the growing short-age of physicians. “In geographies where there are critical shortages of primary care physicians, some insurance companies are even pay-ing retail clinics to act as a medical home,” Charland continued. “If there is no primary care physician, the insurers would rather have somebody than nobody. And they feel that nurse practitioners in these clinics are fully able to act as patients’ primary care providers.”

See Thyroid & Pregnancy, continued on page 2

See Retail Clinics, continued on page 5

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SNAPSHOTKey Online Healthcare Functions

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Patient Demand Physician Capabilities

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2 CLINICAL LABORATORY NEWS NOVEMBER 2012

One of the challenges in raising the pro-file of thyroid health in pregnancy is that the two most common thyroid problems, overt and subclinical hypothyroidism, present like normal pregnancy. “It’s difficult to make the diagnosis of hypothyroidism in pregnancy unless it’s really far advanced be-cause a lot of the symptoms of pregnancy are also symptoms of hypothyroidism. It’s not that physicians aren’t capable of doing so; it’s just that this condition can be crip-pling but in ways that are not obvious,” observed James Haddow, MD. “Fatigue, weight gain, and constipation are part of our lives. So we have to be respectful that it’s not an easy clinical diagnosis. That’s one of the reasons I’m really strongly in sup-

port of routine thyroid function testing, especially during pregnancy.” Haddow, a research professor of pathology and labo-ratory medicine at Brown University in Providence, R.I., has a long-time interest in pregnancy-related thyroid issues, including conducting seminal research on the rela-tionship between thyroid deficiency and pregnancy complications.

The Thyroid in PregnancyDuring pregnancy, rising human chorionic gonadotropin (hCG) levels stimulate the thyroid to produce more thyroid hormone, causing thyroid stimulating hormone (TSH) concentrations to dip below normal, particularly in the first trimester. Elevated hCG levels also lead to temporary increases

in free thyroxine (FT4) and free thyroxine index (FT1) during the first trimester, but in normal pregnancy these measurements usually stay within the nonpregnant range.

Increased estrogen levels in pregnancy also change concentrations of thyroid hormones, most notably thyroid binding globulin (TBG), which rises starting a few weeks into pregnancy and levels off mid-term at about two-to-three times above normal, where it remains until delivery. This increase, in turn, leads to higher levels of total thyroxine (TT4) and total triiodo-thyronine (TT3) throughout pregnancy (See Table, p. 3).

The body’s demand for iodine, which is essential for thyroid function, also in-creases in pregnancy. Several mechanisms are at play, including boosted thyroid hor-mone production brought on by higher levels of hCG and estrogen. The mother’s glomerular filtration rate also rises early in pregnancy, thereby clearing more iodide, and lowering the circulating pool of plasma iodine. In addition, before week 12 of gesta-tion, some maternal iodine stores transfer to the fetus to enable its thyroid gland to start functioning.

What’s the TSH Reference Range?Based on recent research, both the ATA and Endocrine Society recommended trimester-specific reference ranges for TSH, with upper limits of 2.5 mIU/L in the first trimester and 3.0 mIU/L in the second and third trimesters. This com-pares with an upper limit of 4.0 mIU/L in healthy, nonpregnant individuals. Black and Asian women typically have TSH val-ues 0.4 mIU/L lower than in Caucasians, a difference that persists in pregnancy. ATA emphasized the importance of lab- and population-specific reference ranges (See Table, below).

The guidelines define subclinical hy-pothyroidism as a serum TSH level above the upper limit of the trimester-specific reference range but with a normal FT4. Overt hypothyroidism also involves a se-rum TSH level above the upper limit of the trimester-specific reference range, but with a decreased FT4 level. When pregnant women have TSH levels >10 mIU/L, they are considered to have overt hypothyroid-ism regardless of their FT4 levels. Two thirds of undiagnosed pregnant women in this category will become permanently hypothyroid, and an average of 5 years will elapse before a clinical diagnosis is made in the absence of testing.

How Robust are FT4 Assays?Both panels acknowledged challenges with FT4 immunoassays, in that they are sensi-tive to changes in binding proteins. Accord-ing to the ATA panel, “high TBG concen-trations in serum samples tend to result in higher FT4 values, whereas low albumin in serum likely will yield lower FT4 values.” The panel went on to suggest that even though FT4 immunoassays perform rea-sonably well, values should be interpreted using method- and trimester-specific rang-es since studies have shown that reference intervals vary widely between methods. ATA also lauded solid phase extraction-liquid chromatography/tandem mass spec-trometry (LC/MS/MS) in dialysate or ul-trafiltrate as a “major advance” with higher specificity than immunoassays. Although ATA cited the method as being “ideally suited for generating reliable, reproducible trimester-specific reference ranges for FT4,” the panel acknowledged that LC/MS/MS is not widely available. The Endocrine Soci-ety panel also recommended establishing trimester-specific reference ranges for FT4, but in addition suggested either using the

Recommended Trimester-Specific TSH Reference Ranges

First Second Third

0.1–2.5 mIU/L 0.2–3.0 mIU/L 0.3–3.0 mIU/L

Source: Thyroid 2011;21:1081–125

FT4 Immunoassays Not Always ReliableThyroid & Pregnancy, from page 1

Risk Factors for Targeted Thyroid Function Testing in Pregnancy

® Age >30 years

® Family history of thyroid disease

® History of thyroid dysfunction or surgery

® Goiter

® Thyroid antibody positivity

® Symptoms suggestive of hypothyroidism

® Type 1 diabetes

® History of miscarriage or preterm delivery

® Autoimmune disorders associated with autoimmune thyroid dysfunction

® History of head or neck irradiation

® History of infertility

® Morbid obesity

® Treatment with amiodarone, lithium, or levothyroxine

® Recent exposure to iodinated radiological contrast agents

® Current residence in a region with presumed iodine deficiency

Source: Thyroid 2011;21:1081–125; J Clin Endocrinol Metab 2012;97:2543–65.

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CLINICAL LABORATORY NEWS NOVEMBER 2012 3

free T4 index or multiplying the nonpreg-nant TT4 range, 5–12 μg/dL, by 1.5.

“Many FT4 immunoassays are not ter-ribly robust in pregnancy because the very high TBG levels seem to throw off the results in unpredictable ways. A number of stud-ies suggest that most commercially available FT4 assays may be unreliable in pregnancy,” said ATA panelist Elizabeth Pearce, MD, MSc. “The ATA official recommendation was solid phase extraction LC/MS/MS, which is available in select locations. It does work very well, but almost no one has it. We came to the conclusion on our panel that in the absence of access to a gold-standard assay you have to know your local assay, de-velop a feel for how it works in pregnancy, and be aware that the TSH is a more reli-able measure in most circumstances. The Endocrine Society panel also had concerns about the usefulness of most of the FT4 assays in pregnancy, but they specifically recommended use of the free thyroxin in-dex. That’s one of the more significant dif-ferences between the guidelines.” Pearce is an associate professor of medicine at the Boston University School of Medicine.

Making the Outcomes ConnectionThe association between maternal thyroid hormone and iodine levels and outcomes for both mother and baby have been the focus of considerable research and contro-versy. Overt hypothyroidism in pregnancy clearly has been linked to increased risk of premature birth, low birth weight, and miscarriage. Evidence about how subclini-cal hypothyroidism affects pregnancy out-comes has been less consistent.

Studies also have associated maternal hypothyroidism with cognitive challenges in offspring, albeit with conflicting results. Reports dating to the early 20th century showed a correlation between mothers with iodine deficiency and mental retarda-tion in their babies, but in the modern era,

research involving pregnant women with less severe hypothyroidism unrelated to io-dine deficiency has yielded less consistent findings. Haddow’s study from 1999 found that children ages 7–9 years born to women

with overt, undiagnosed hypothyroidism during pregnancy were more likely than controls to have an IQ 85 as well as motor, language, and attention delays, but the as-sociation was not statistically significant. To the disappointment of many in the field, re-sults from a long-awaited randomized trial published in February found that antena-tal screening and maternal treatment for hypothyroidism did not lead to improved cognitive function in children at 3 years of age (N Engl J Med 2012;366:493–501).

Is Universal Screening Warranted?Lack of research definitively linking screen-ing and intervention for subclinical hy-pothyroidism to improved outcomes has evoked considerable debate in the endo-crine and obstetrical communities. The ATA guideline committee ultimately deter-mined that there was not enough evidence

to recommend for or against either uni-versal TSH or FT4 screening in pregnant women or preconception TSH screening in women at high risk of hypothyroidism. However, the committee did recommend TSH testing early in pregnancy in women at high risk for overt hypothyroidism (See Table, left).

Reflecting the controversy in this area, the Endocrine Society committee could not reach a consensus on whether all newly pregnant women should have TSH test-ing. Five panelists supported screening all pregnant women at their first obstetrical visit, while eight others were neither for nor against universal screening, though they strongly supported aggressive case find-ing to identify and test high-risk women. Meanwhile, the American College of Ob-stetricians and Gynecologists and Society

Thyroid Function Test Results in Thyroid Disease

TSH Free T4

Overt hypothyroidism i m

Subclinical hypothyroidism i Normal

Normal pregnancy Normal Normal

Hypothyroxinemia Normal m

Overt hyperthyroidism m i

Source: ACOG Practice Bulletin 37, 2002; SFMF Consult from Contemporary OB/GYN, August 2012

See Thyroid & Pregnancy, page 4

Thyroid in Pregnancy

Learn more during AACC’s upcoming Webinar,

Effective Laboratory Testing for Thyroid Health during Pregnancy

November 13

Register online at: www.aacc.org/events

or call 1-800-892-1400.


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for Maternal-Fetal Medicine recommend against routine testing during pregnancy.

Sullivan summarized the divergent opin-ions and lively discussion on this subject. “There’s a group of people who feel passion-ately for all the right reasons that everyone should be screened. Other experts feel be-cause of the lack of data and because of cost it shouldn’t be done. Then there are people in the middle, like me, who have sympa-thy for both points of view. Being on both panels, I can’t count the number of hours that I’ve heard the arguments. It was a close call.” The endocrinology community, he explained, “favors screening because they’re really concerned about prenatal outcomes. However, the obstetrical community is more cautious and conservative. We’ve been burned by screening programs in the past, incompletely thought out and based on in-complete data, that now we’re stuck with. We also have more of a medical liability crisis than other specialties, so if there’s a recom-mendation or guideline and you stray from it, you open yourself up to litigation.”

Supporters of universal screening now are looking forward to results from an on-going study of subclinical hypothyroidism in pregnancy sponsored by the National Institute of Child Health and Human De-velopment, which is not expected to pub-lish results for at least a couple of years. The ATA panel acknowledged the evolving science in this area. “The committee rec-ognizes that knowledge on the interplay between the thyroid gland and pregnancy/postpartum is dynamic, and new data will continue to come forth at a rapid rate. It is understood that the present guidelines are applicable only until future data refine our understanding, define new areas of impor-tance, and perhaps even refute some of our recommendations,” wrote the panel.

Given the conflicting guidelines and in-complete and inconsistent evidence, TSH testing patterns in pregnant women appear to be all over the map. In a study published last year, Pearce found that 85% of women being followed at Boston Medical Center were screened during their first obstetri-cal visit. Meanwhile, Quest Diagnostics in 2012 reported that overall, 23% of the more than 500,000 for whom it performed pregnancy-related testing had TSH testing (J Clin Endocrinol Metab 2012;97:777–84). Haddow also reported finding that about half the pregnant women in Maine were routinely being tested for TSH levels.

“I think there’s a huge amount of re-gional variation,” observed Pearce. “In the setting of conflicting guidelines, people are doing a variety of different things, and whatever they’re doing there’s probably a guideline out there to support it.”

What’s the role of TPO Antibodies?If the guidelines diverged somewhat on TSH and FT4 testing, they concurred in not en-dorsing universal thyroid antibody screen-ing in pregnancy. A recent prospective trial and some retrospective studies have found the risk of pregnancy complications to be more pronounced in women who have both subclinical hypothyroidism and who are anti-thyroid peroxidase antibody (TPOAb) positive. Both TPOAb and thyroglobulin antibody positivity also have been associated

with pregnancy loss, but noting that an asso-ciation does not equate to causality, the ATA panel found insufficient evidence for thyroid antibody screening.

In Sullivan’s experience, confusion about thyroid antibody testing causes it to be underutilized, even in cases in which it could help resolve other inconclusive tests. This presents a real opportunity for labo-ratorians to step in and help clinicians, he argued. “When I talk to other obstetricians, they like to hear about iodine deficiency and screening for subclinical hypothyroid-ism, but when I start talking about antibod-ies, they just tune me out. That’s an area where we have a lot of work to do, because there still remains a lot of confusion,” he explained. “There are so many different names for the same thing. TPO and anti-peroxidase antibodies, for example. People don’t know those are the same thing. When I’ve spoken to non-specialist obstetricians they’ve all but abandoned ordering these tests because it’s so frustrating for them, and that’s a disservice.”

User-friendly TestingExperts consulted for this article agreed that TSH by far is the most important test of thyroid function in pregnant women, although Haddow and others emphasized the importance of establishing trimester-specific reference ranges and providing interpretive comments to aide physicians in evaluating test results in the context of patients’ clinical status.

“My feeling at the moment is that mea-surements of FT4 and TPO antibodies can contribute useful supplementary informa-tion when TSH is outside the reference range, even though there can be certain instances when FT4 assay values don’t cor-relate with the original dialysis method. It should be possible to perform them in a straightforward manner,” observed Had-dow. “That said, the obstetric community is somewhat confused right now because of the conflicting recommendations, and the laboratory has a responsibility to provide not just the test result but an interpretive statement that’s based on the recommend-ed trimester-specific cutoffs. That will go a long way in terms of helping the physician.”

Shannon Sullivan, MD, PhD, also ar-gued for some way, either by electronic health record or test requisition form, for a physician to be able to inform the lab that a patient is pregnant, thereby facilitating bet-ter communication between the two. “If a pregnant woman came in with a TSH of 15 mIU/L, I’d consider that a critical lab value, but it certainly would not be called into the physician as critical because the lab typical-ly wouldn’t be aware the patient is actually pregnant,” she said. “On the lab requisition form there could be a box the physician could check to indicate that the patient is pregnant. I’ve never seen that before, but it would give the person who is running the test and reporting back to physicians any critical values a heads up that this lab value is abnormal for a pregnant person.” Sulli-van, unrelated to Scott Sullivan, is an endo-crinologist at Washington Hospital Center and an assistant professor of medicine at Georgetown University School of Medicine in Washington, DC.

Another area of concern to both Sul-livans is occult iodine deficiency. Both guidelines recommend 250 μg iodine daily in pregnant women. However, probably in deference to the U.S. overall being an io-dine replete country, the Endocrine Society guidelines explicitly do not advise as part of normal practice measuring urine iodine concentration (UIC), which, while being a validated measure of population iodine status, is not reliable for individuals, due to wide day-to-day and diurnal variations. Yet both Sullivans are seeing in their respective practices growing numbers of patients who are iodine deficient, sometimes severely so. Both attributed this to a confluence of factors, including public health adviso-ries about the need to decrease salt intake and for pregnant women to avoid tuna, the growing popularity of non-iodized sea salts, and reliance on processed foods, which do not use iodized salt. In addition, not all prenatal vitamin formulations con-tain iodine.

How this trend will be incorporated in future guidelines or factored into test-ing patterns remains to be seen. In the meantime, experts emphasized that labo-ratorians are important players in guiding physicians through the complex and some-times confusing domain of thyroid func-tion testing in pregnancy. CLN

References and Resources for Thyroid Disease in Pregnancy

® De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2012;97:2543–65.

® Negro R, Mestman JH. Thyroid disease in pregnancy. Best Pract Res Clin Endocrinol Metab. 2011;25:927–43.

® Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011;21:1081–125.

® Gronowski AM, Haddow J, Kilpatrick S, et al. Thyroid function during pregnancy: Who and how should we screen? [Epub ahead of print] Clin Chem June 6, 2012 doi:10.1373/clinchem.2012.185017.

® Vissenberg R, van den Boogaard E, van Wely M, et al. Treatment of thyroid disorders before conception and in early pregnancy: a systematic review. Hum Reprod Update 2012;10:361–77.

® Yazbeck CF, Sullivan SD. Thyroid disorders during pregnancy. Med Clin N Am 2012;96:235–56.

Using TPO Ab Results Remains ChallengingThyroid & Pregnancy, from page 3


Growth Signals TurnaroundRetail clinics first began making news in 2000, but after an initial jump, some closed their doors only a few years later, with some observers calling the model a failure. Since the mid 2000s, however, the industry has rebounded, with more than 1,300 clinics around the country and nearly 12% growth in 2011, according to Charland. Industry leader MinuteClinic opened 19 new clinics just in September.

While CVS Pharmacy’s MinuteClinic and Walgreens’ Take Care Clinic still domi-nate, Target and Walmart are expanding their clinic presence, and dozens of health systems are opening their own retail-style clinics, such as Geisinger’s Careworks walk-in clinics (See Box, p. 6).

Retail clinics are also adding new tests that go far beyond caring for scraped knees and scratchy throats. The growing list of tests includes lipid panels, HbA1c, microal-bumin, HIV, fecal occult blood, influenza A and B, and even screening for methicillin-resistant Staphylococcus aureus. Clinics of-fer many of these tests as part of adult and child physicals, and more recently, Medi-care wellness visits (See Box, p. 7).

A recent study found that patient traffic to retail clinics doubled every year between 2007 and 2009, reaching nearly 6 million visits in 2009 (Health Aff 2012;31:2123–29). Patients spent an average of $78 per visit, which translated into about $460 mil-lion in 2009. While a significant amount of this volume was attributed to flu shots—an area in which pharmacies now compete more than they did in 2009—the study showed that consumers increasingly ac-cept and value the convenience of clinics. The authors noted that nearly 50% of re-tail clinic visits take place during hours that physician offices are not open.

Laboratorians will feel little comfort knowing they are not the only healthcare professionals worried about a staffing shortage. The American Association of Medical Colleges warns that by 2020, the nation will face a shortage of 45,000 pri-mary care physicians. This crisis will be-come especially serious when, in 2014 and beyond, the healthcare reform law reaches full effect, pulling some 30 million people into the healthcare system through Medic-aid and subsidized private insurance.

The expected influx of newly insured patients under the Affordable Care Act pro-vides both opportunity and uncertainty for the retail clinic model, according to the lead author of the study, Ateev Mehrotra, MD. “If more people are seeking primary care, and there is no dramatic increase in the number of primary care physicians, we could face a situation of increased demand and worsening access. Without an alterna-tive, more patients may go to a retail clinic,” he said. “The flipside is that a significant segment of patients who go to a retail clinic don’t have a primary care physician. If un-der healthcare reform more people gain access to primary care physicians, it’s still possible they could choose the physician’s office over the retail clinic.” Mehrotra is a policy analyst at the RAND Corporation and an associate professor of medicine at the University of Pittsburgh School of Medicine.

Notably, in Mehrotra’s study, nearly 70% of patients were covered by insurance. This figure was no surprise to Charland, who emphasized that retail clinics cater mainly to middle-class families. “The biggest driver for retail clinics is still convenience. There is this fallacy out there that all these clinics do is ca-ter to the uninsured. And that’s just not true,” Charland said. “It’s busy, dual-income, edu-cated, working parents whose kids are also busy. When someone gets sick in the house-hold, it’s chaos. And for the doctor’s office to say they can only see you on a certain day at a certain time, that just doesn’t cut it any-more.” Charland has been involved in retail medicine since 2003. He served as senior vice president of strategy and business develop-

ment at MinuteClinic and helped develop the company’s early relationship with CVS Pharmacy, as well as with insurers.

In addition to more patients with insur-ance, changes to insurance plans them-selves will drive patients to retail clinics as well, Charland predicted. “High-deductible health plans, which are expected to become more common, will also mean growth for retail clinics,” he said. “The transparency of pricing is important to people because it’s now coming directly out of their pockets. And you don’t have the situation where you don’t know what you paid until 60 days lat-er when the explanation of benefits comes in the mail. Healthcare is the only industry in this country where you can buy some-thing, and you don’t know what you paid for it. But that’s not the case with retail clin-ics, and people are drawn to that.”

Collaborations Deepen Ties to Healthcare SystemEarly on, the largest chains of retail clinics entered the market as an extension of na-tional pharmacies, such as MinuteClinic in CVS and Take Care Clinic in Walgreens. Today, many clinics partner with health sys-tems outside the walls of the store in which they reside. For example, MinuteClinic now has deals with 18 health systems, represent-ing more than 150 hospitals. Walmart also has deals with more than 12 health systems or physician groups, representing some 137 clinics.

In one of the most recent collabora-tions, the University of California, Los Angeles (UCLA) announced in July that UCLA Health System physicians will serve as medical directors for 11 MinuteClinics

See Retail Clinics, continued on page 6

Clinics Expand Locations, ServicesRetail Clinics, continued from page 1

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in Los Angeles County. They also will work together on patient education and disease management programs. Tightening the re-lationship, MinuteClinic and UCLA already have started to work toward fully integrat-ing their electronic health record (EHR) systems in order to share medical histories and visit summaries with other UCLA loca-tions. In announcing the deal, UCLA Health System president David Feinberg, MD, noted that UCLA hoped to “explore new and innovative ways to deliver patient care and manage chronic conditions.”

UCLA’s Bernard Katz, MD, told CLNthat for the most part, physicians at UCLA have supported the partnership. “There may be some primary care physicians who feel that this is a competition for the same patients, but I think that most understand that these clinics are facilities where their patients can get care in a kind of outreach setting that is like an extension of their of-fice,” he said. “In these days of more and more difficult access to primary care, we think this partnership will open up new avenues for our patients to get the high-quality care that they need.”

Katz, who is the physician coordina-tor of the MinuteClinic collaboration, also noted that MinuteClinic will ask patients if

they have a primary care relationship, and if they don’t, encourage them to establish one. The plans for how MinuteClinic might help UCLA manage chronic conditions such as diabetes and hypertension are still in the early stages, but they revolve around sharing information via EHR.

As health systems move toward an ac-countable care organization (ACO) model that emphasizes outcomes and efficiency, collaborations with retail clinics could be part of the strategy. “Because accountable care is about population management, MinuteClinic could be a great way for pa-tients who are part of the UCLA health system to have better access to care that is convenient and still coordinated through the EHR in an ACO model,” he said. UCLA is still in the process of assessing how it will adapt to the ACO model.

Widening Scope of Care Sparks CriticismAs retail clinics have grown in number and ventured into the sphere of chronic disease management, they have also met with stern criticism from some physician groups, such as the American Medical Association (AMA) and the American Academy of Family Physicians (AAFP).

AAFP has been vocal in opposing any expansion of the scope of service in retail

clinics that approaches managing chronic conditions. It believes that high quality and coordinated care depend on relationships with primary care physicians—a relation-ship with which retail clinics interfere.

“AAFP believes that the best healthcare comes from a patient-centered medical home, where you have a strong primary care focus with comprehensive, coordinat-ed, and continuing care,” said AAFP presi-dent Jeffrey Cain, MD. “When retail clinics start talking about managing chronic dis-ease or performing well adult exams, that’s further fragmenting an already fragmented health system. We believe patients will have better care and better quality if they find that care within an ongoing relationship to a primary care physician who knows that person.” Cain is chief of family medicine at Children’s Hospital Colorado and asso-ciate professor in the Department of Fam-ily Medicine at the University of Colorado Health Sciences Center in Aurora.

According to Cain, family physicians have responded to the demand for greater flexibility by expanding access to appoint-ments. “Family doctors have responded so that about 75 percent of their offices have open-access, same-day appointments and about half have evening or weekend office hours,” he said. Results from an AAFP phy-sician survey also found that about 31% of respondents offered weekend appointments.

Both AMA and AAFP are urging insur-ers not to give patients an incentive to use retail clinics, warning of the potential for duplicative tests and treatments, higher costs, and lower quality.

Tine Hansen-Turton, executive director of the Convenient Care Association (CCA), which represents retail clinics, admits that retail clinics amount to “disruptive innova-tion.” However, she emphasized that the in-dustry has committed to quality and safety standards. These include sharing informa-tion with patients’ primary care providers, using EHRs, referring patients without primary care physicians to these provid-ers, making prices transparent, and using evidence-based guidelines.

CCA member clinics also are com-mitted to patient follow-up. For example, nurse practitioners regularly call patients after visits—usually the next day—to check their status and confirm whether any pre-scriptions were filled. “The nurse will also take the opportunity to again encourage the patient to get connected to a primary care practitioner if they aren’t already,” Hansen-Turton said. “I think that is how we have gained a lot of credibility in the lo-cal medical communities where our clinics operate, because they are feeders now into primary care.”

Charland believes that some physician groups oppose the expansion of retail clin-ics simply because of a concern over com-petition. “It’s interesting that this argument against fragmented care only emerged when retail clinics came to be. I don’t really buy this argument or the quality argument. I think it’s purely economic. These are the bread and butter, easy visits for physicians. If it’s fragmented care, it’s been there for a lot longer than retail clinics have been, and it’s fragmented because physician offices

Chronic Disease Care Irks DocsRetail Clinics, continued from page 5

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Retail Clinics Expand, Diversify Operator Clinics

MinuteClinic 588

TakeCare 356

Walmart Partners 143

The Little Clinic 89

Target Clinic 53

FastCare 31

RediClinic 29

Dr. Walk-In Medical Clinics 13

Aurora QuickCare 10

Lindora Health Clinics 9

Alegent Quick Care 6

Family Quick Care 5

Geisinger Careworks 5

As of October 1, 2012. Source: Merchant Medicine LLC


make it that way, by making it so inconve-nient that people are forced to find alterna-tives.”

Charland emphasized that he sees little difference between a physician overseeing a nurse practitioner in a doctor’s office versus reviewing what nurse practitioners docu-ment after seeing patients in retail clinics. “When physicians have nurse practitioners in their offices, they certainly don’t see ev-ery patient the nurse sees. So now with a retail clinic there is a nurse practitioner a quarter mile down the street. There is no difference than when the physician looks at a record after the fact for the patient in either case. This is an economic impact on the physician, no two ways about it.”

No one has specifically studied the quality of testing at retail clinics. How-ever, other CLIA-waived sites such as doc-tors’ offices that the Centers for Medicare and Medicaid Services (CMS) has studied do not have a perfect record. CMS began studying CLIA-waived testing sites in 2002, and found that more than 20% of those surveyed didn’t perform quality control as detailed in manufacturers’ instructions and 13% didn’t even have these instructions. According to CMS, the agency continues to survey about 2% of CLIA-waived labs each year, and finds similar results. CMS has plans for a new educational program to try and improve upon these numbers.

With Expansion, More Testing LikelyExperts on retail clinics agree that services will continue to broaden, but what this will mean for diagnostics is uncertain. For the most part, retail clinics rely on CLIA-waived tests that they can perform on-site, and the small space and need for speedy appointments limits the kind of tests that can be performed.

Hansen-Turton noted that diagnostic companies regularly approach CCA seek-ing to find a place for their rapid tests. “A lot of different companies come to us from the diagnostic area, and we often bring them in to our members to get their thoughts,” she said. “We try and help our members take advantage of some of these new technolo-gies from diagnostic companies that can work within a very small footprint. We are going into a new expansion, and you will notice more growth and an evolution of services, but still within the framework of what can you do in a 15 to 20 minute visit.”

More testing also goes hand-in-hand with the desire of clinics to enhance their offerings and avoid depending on services for which demand can come and go with the seasons, such as flu shots or children’s sports physicals. “I think retail clinics in general would love to be able to provide more services, and certainly more tests would facilitate that,” said Mehrotra. “The limitation is that usually they only have one nurse practitioner on site, and blood draws add a level of complexity.”

Like the growth of other services retail clinics offer, payers ultimately will be the driving force behind more testing, according to Charland. “What will generate testing vol-ume is insurance companies putting an in-centive out there for people to go get tests—and that could be a carrot or a stick,” he said. “In an ACO type of risk arrangement, where

a health system takes on the risk of a popu-lation’s health, they’ll want to find ways to efficiently monitor chronic diseases. If that health system decides that MinuteClinic is the most efficient way to get that done, that’s what will change it. It will be some sort of incentive for the patient. And we definitely see that starting to happen.”

Courting the Walk-In PatientAs healthcare becomes more competitive, more patient-focused, and more sensi-tive to cost, retail clinics and other non- traditional outreach settings could be es-sential for health systems. “A key benefit of retail clinics run by health systems is that they serve as an entry point for new pa-tients,” Mehrotra commented. “Drawing new patients into their primary care and specialty system is critical.”

With health systems and retail clinics experimenting with new services and new partnerships, the lines between urgent care centers, retail clinics, and other kinds of outreach settings also will blur, Charland predicted. “There used to be three unique markets, but there is now significantly more convergence as they compete with each other for that walk-in patient,” he said. “And there is all kinds of activity in this space that I think is positioning it for the future, which is when we will no longer pay for healthcare mostly on a transaction-by-transaction basis, but instead will pay for outcomes, the ACO concept. If that really takes hold, the economic incentives change, and suddenly there is not a threat, but rather an incentive to find a way to get that illness treated in the most efficient way possible.” CLN

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Follicle Stimulating HormoneHuman females are born with a finite amount of oocytes. Oocyte loss via apop-tosis occurs throughout the lifespan, even in prepubertal females. For reproductive age females, cyclic cohorts of oocytes be-gin development in any given menstrual cycle, but typically only one becomes fully mature and is ovulated. Although there is significant individual variation, in general, oocyte quantity and quality begin to de-cline rapidly around age 37 and continue to fall until the oocyte supply is exhausted in menopause.

Determining a woman’s relative ovarian reserve, or quantity and quality of oocytes, is a critical early part of the initial infertility evaluation. Although testing protocols vary, most IVF centers use a combination of lab-oratory studies and ovarian imaging via ul-trasound to determine ovarian reserve and help guide fertility therapy.

High serum follicle stimulating hor-mone (FSH) concentrations in the early part of the menstrual cycle are a well-known predictor of reproductive aging; therefore, clinicians for many years have

used FSH testing as a component of ovar-ian reserve testing. To determine ovarian reserve, clinicians measure a woman’s FSH value at its nadir early in the follicular phase, cycle days 2–3. While FSH is strongly as-sociated with reproductive age, it also var-ies during a woman’s lifetime, as well as throughout a typical menstrual cycle. Given this large amount of variation, many studies have demonstrated that maternal age, rather than FSH value alone, may be more predic-tive of IVF success (1). FSH values >10 IU/L seem to have high specificity for predict-ing poor response to ovarian stimulation,

but the sensitivity at this value is low unless FSH is at a high threshold value.

Very high levels of FSH, however, seem to be predictive of poor pregnancy outcome. In one recent study, FSH levels >18 IU/L resulted in no live births (2). Consequently, some fertility programs have FSH thresholds above which women are not offered IVF ser-vices due to the low probability of success.

EstradiolEstradiol (E2) is a steroid hormone se-creted into circulation by granulosa cells of

developing ovarian follicles. Clinicians also commonly measure E2 levels in women as part of ovarian reserve testing. Levels of this hormone in reproductive age women fluctuate from 10–300 pg/mL, depending on timing of the menstrual cycle (3). For ovarian reserve testing, clinicians typically assess E2 levels at their nadir early in the menstrual cycle, at days 2 or 3.

Assessing levels of these hormones at a consistent time point in the menstrual cycle allows clinicians to make meaningful interpretations of the values. For example, a high basal FSH or E2 level suggests im-paired oocyte development early in the menstrual cycle—a worrisome sign of re-productive aging and/or poor ovarian re-serve. In addition, because estradiol exerts negative feedback on FSH secretion from the pituitary gland, high E2 (>100 pg/mL) can inhibit FSH secretion, resulting in an artificially low FSH value.

Despite being a simple, inexpensive, and effective screening tool, basal E2 levels alone have a low predictive value for IVF outcome. In a systematic review of 3,352 patients being treated for IVF, researchers actually found conflicting results (4). In some studies, lower IVF success rates were reported for both low and high E2 levels, whereas others found that baseline E2 levels have no effect on IVF success. In yet anoth-er study, researchers discovered that a basal estradiol level >75 pg/mL was associated with poor IVF outcomes and pregnancy rates (3). Given these inconsistencies, the best use of E2 levels in combination with baseline FSH values has been in determin-ing the appropriate medication doses to start an IVF cycle or for deciding to forego treatment altogether when the probability of success is low.

In addition to baseline ovarian function, clinicians frequently evaluate wom-en’s E2 levels in a controlled-ovarian- hyperstimulation (COH) setting to moni-tor follicular development. As follicles de-velop, E2 levels steadily increase. During a spontaneous cycle, E2 levels typically peak between 250–300 pg/mL as ovulation ap-proaches. In contrast, when superovulation —release of more than one mature oocyte —is the goal, women in a COH cycle have significantly higher E2 values (Figure 1).

In both COH and IVF cycles, clinicians use E2 levels to determine the risk of ovarian

Fertility TestingHow Laboratory Tests Contribute to Successful Infertility TreatmentsBY ABIGAIL DELANEY, MD, JANI R. JENSEN, MD, AND DEAN MORBECK, PHD

Infertility is a common clinical problem affecting an estimated 15% of couples worldwide. According to the

2006 National Survey of Family Growth, approximately 7.4 million women age 15–44 in the U.S. reported

receiving any type of infertility service. But with current technology, women who undergo infertility treat-

ments enjoy much improved success rates.

Infertility treatments can consist of an extensive clinical evaluation, including multiple laboratory and

imaging studies. Laboratory testing for female hormones plays a large part in both the work up for infertility and

monitoring during treatment. This review will discuss the laboratory tests commonly used for these purposes,

including tests of importance during in vitro fertilization (IVF) cycles.

CLN’S

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hyperstimulation syndrome (OHSS), a self-limited but occasionally severe response to ovarian hyperstimulation. In a retrospec-tive analysis of IVF patients, researchers defined OHSS risk groups according to estradiol levels (5). In 637 IVF cycles, no patients developed OHSS with peak E2 lev-els <3500 pg/mL, 1.5% developed hyper-stimulation with peak E2 levels 3500–5999 pg/mL, and 38% developed OHSS with E2 levels >6000 pg/mL. While many factors contribute to cycle monitoring and pre-vention of OHSS, studies have shown that monitoring E2 levels reduces incidence of OHSS. Although the upper threshold of E2 that confers the highest risk of OHSS is in-consistent in the literature, most clinicians agree that risk of OHSS with a peak E2 level <3000 pg/mL is low risk (1).

Anti-Müllerian HormoneAnti-Müllerian hormone (AMH) is a di-meric glycoprotein and a member of the transforming growth factor-beta super-family, which, like estradiol, is secreted by granulosa cells of pre-antral and antral follicles in the ovary. Serum AMH lev-els reflect the overall follicular pool, and several research teams have evaluated AMH as a marker of ovarian reserve. In general, high AMH levels correlate with good ovarian reserve and vice versa. Fur-thermore, AMH is undetectable 3–5 days following bilateral ovariectomy. Several research groups also have demonstrated a correlation between low AMH levels and menopause (6).

In addition to its role in evaluating ovar-ian reserve, researchers have studied AMH as a predictor of response to gonadotropin stimulation during ovulation induction. Over the natural course of ovarian stimu-lation, AMH levels gradually decline. Ad-ministering FSH exogenously to women leads to an increase in follicular size and E2 levels, both of which have been implicated as regulators of AMH secretion.

Several studies also have demonstrated a strong correlation between basal AMH levels and number of oocytes retrieved

during an IVF cycle, including one in which basal AMH levels were found to be 2.5 fold higher in patients who had >11 oocytes re-trieved. In a meta-analysis, AMH appeared to be a better predictor of response to ovar-ian stimulation than patient age and day-3 FSH, E2, or inhibin B levels (7). The studies comparing AMH to antral follicle count for predicting response to ovarian stimulation found no significant difference between these two analytes (7).

Poor response to ovarian stimulation occurs in approximately 2–30% of IVF cycles. While not all IVF programs use the same definition, most classify women as poor responders based on low follicle num-ber (<3–5) and retrieved oocytes (<3–5), as well as on cancellation of a cycle due to inadequate stimulation. La Marca et al (7)

published the first study evaluating AMH as a tool for predicting poor response to controlled ovarian hyperstimulation. They found AMH had a sensitivity of 80% and specificity of 93%; however, the accuracy of AMH for predicting poor response to COH was not consistently reproducible. These findings suggest that a low response is not a good reason to exclude patients from IVF.

On the opposite end of the spectrum, AMH also may be useful for predicting OHSS. This hypothesis is based on the idea that an exaggerated response to gonado-tropins may be secondary to high AMH. Two prospective trials have demonstrated that basal levels of AMH >3.5 ng/mL are associated with OHSS. Further studies are needed to determine whether stimulation

treatment should be stratified based on AMH levels to avoid OHSS (7).

Inhibin BInhibin B is one of the beta subunits of the dimeric protein inhibin, and like AMH, it is produced by pre-antral and early antral follicles. Inhibin B values vary during a woman’s reproductive lifetime and men-strual cycle. In addition, changes in inhibin B levels that occur with reproductive aging are similar to those of FSH and AMH. As women age, FSH levels increase, and both inhibin B and AMH decrease. Decline in in-hibin B level is a late marker of diminished ovarian reserve; therefore, inhibin B values cannot be used to predict ovarian failure or menopause (8). Currently, inhibin B levels are not regarded as a standard and/or reli-able assessment of ovarian reserve (6).

Administering exogenous gonadotro-pins for controlled ovarian stimulation re-sults in an increase in inhibin B, and studies have demonstrated that poor responders generally have lower inhibin B levels. In fact, serum levels of inhibin B <45 pg/mL have been associated with poor response to gonadotropins, as well as high rates of cycle cancellation, reduced IVF retrieval, and lower clinical pregnancy rates (9).

ProgesteroneProgesterone levels are a simple measure-ment of ovarian function. Progesterone lev-els remain low during the follicular phase (<1 ng/mL), rise on the day luteinizing hormone (LH) surges (1–2 ng/mL), and increase steadily until they peak approxi-mately 1 week after ovulation. Progesterone levels <3 ng/mL imply anovulation, except when assessed immediately after a woman ovulates or prior to menses when proges-terone levels are at a physiological low. To assess for presence or absence of ovulation, clinicians typically assess a woman’s pro-gesterone levels approximately 1 week be-fore the expected onset of menses (6).

Clinicians often use gonadotropin-releasing hormone (GnRH) analogues to induce ovulation and suppress the

Table 1

Laboratory Tests Used for Fertility TestingLaboratory Test Normal Values When to Measure Important Points

Follicle Stimulating Hormone (FSH)

5–20 mIU/L Follicular phase, days 2–3 of menstrual cycle

FSH values >10 IU/L predict poor response to ovarian stimulation (1)

FSH values >18 IU/L predictor of poor pregnancy outcome (2)

Estradiol (E2) 20–400 pg/mL Follicular phase, days 2–3 of menstrual cycle

Helpful in combination with FSH to establish baseline ovarian reserve

Use with monitoring of COH. Low risk of OHSS with E2 value <3000 pg/mL

Anti-Müllerian Hormone

0.9–9.5 ng/mL Not cycle dependent so can be measured at any time

Low values (0.2–0.7 ng/mL) predict poor response to COH but are not useful in predicting pregnancy (6)

Inhibin B <139 pg/mL during the follicular phase

Follicular phase, days 2–3 of the menstrual cycle

Serum levels <45 pg/mL have been associated with poor response to gonadotropins (9)

Progesterone Follicular phase: <3 ng/mL

Secretory phase: 5–30 ng/mL

One week prior to expected menses to assess for ovulation

Values <3 ng/mL during the secretory phase indicate anovulation

Lutenizing Hormone (LH)

5–20 mIU/mL Mid-follicular phase Studies vary in regard to clinical value of LH

Abbreviations: COH: controlled-ovarian-hyperstimulation; OHSS: ovarian hyperstimulation syndrome.

Figure 1

Estradiol and Follicular Diameter in IVF by Day of Stimulation

Both estradiol and average follicular diameter increase throughout a typical cycle.


pituitary, thereby preventing premature LH surge and subsequent ovulation. However, many studies describe a find-ing called premature luteinization that occurs in 5–30% of cases. This happens when patients’ serum progesterone levels rise higher than a defined threshold value of 0.9–1.2 ng/mL, despite their having received GnRH. Some clinicians suspect that if a woman’s serum progesterone is elevated on the day ovulation is induced, the success of the IVF cycle is adversely af-fected, although this has been the subject of debate for many years. A recent meta-analysis of 12 studies concluded that the probability of clinical pregnancy in IVF cycles did not differ significantly between patients with elevated progesterone and those with normal levels on the day of administering the human chorionic go-nadotropin trigger (10).

Luteinizing Hormone As stated in the previous section, inhibiting premature LH surge during ovarian stimu-lation for IVF has been a clinical standard for many years. Multiple studies have been conducted on the role of LH concentra-tions with regard to both oocyte quality and the endometrium. Two prospective studies suggested that the higher the mid-follicular endogenous LH level, the lower the prob-ability of ongoing pregnancy achieved via IVF. In comparison, a recent meta-analysis demonstrated there was no association be-tween low LH levels and decreased success of an ongoing pregnancy achieved via IVF (11).

Reasons to CelebrateToday, more than 1% of all infants are born with assisted reproductive technol-ogy, a statistic expected to rise as mean

maternal age continues to increase. While the workup for infertility can be extensive, laboratory tests can help de-termine primary diagnosis and assess ovarian reserve (Table 1). Most impor-tantly, the results of these tests provide a predictive framework for managing and treating infertility.

As technology continues to improve, laboratory testing will undoubtedly be-come a more accurate and sensitive predic-tor of response to COH, making treatment of infertility safer and more effective for women. There are many reasons to cel-ebrate now, however, as more and more infertile couples welcome babies born with these assisted technologies. CLN

REFERENCES1. Broekmans FJ, Kwee J, Hendriks DJ, et al. A systematic review of tests predicting

ovarian reserve and IVF outcome. Hum Reprod Update 2006;12:685–718.

2. Scott RT Jr, Elkind-Hirsch KE, Styne-Gross A, et al. The predictive value for in vitro fertility delivery rates is greatly im-pacted by the method used to select the threshold between normal and elevated basal follicle-stimulating hormone. Fertil Steril 2008;89:868–78.

3. Buyalos RP, Daneshmand S, Brzechffa PR. Basal estradiol and follicle stimulat-ing hormone predict fecundity in women of advanced reproductive age undergoing ovulation induction therapy. Fertil Steril 1997;68:272–7.

4. Kosmas I, Kolibianakis E, Devroey P. Association of estradiol levels on the day of hCG administration and pregnancy achievement in IVF: a systematic review. Hum Reprod 2004;11:2446–53.

5. Asch RH, Li HP, Balmaceda JP, et al. Severe ovarian hyperstimulation syndrome in assisted reproductive technology: defi-nition of high-risk groups. Hum Reprod 1991;6:1391–9.

6. Speroff L, Fritz MA. Clinical gyneco-logic endocrinology and infertility, 8th Ed. Philadelphia: Lippincott Williams and Wilkins 2011:1293–1383.

7. La Marca A, Sighinolfi G, Radi D, et al. Anti-Müllerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update 2010;16:113–30.

8. van Rooij IA, Broekmans FJ, Scheffer GJ, et al. Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study. Fertil Steril 2005;83:979–87.

9. Seifer DB, Lambert-Messerlian G, Ho-gan JW, et al. Day 3 serum inhibin-B is pre-dictive of assisted reproductive technolo-gies outcome. Fertil Steril 1997;67:110–4.

10. Venetis CA, Kolibianakis EM, Papan-ikolaaou E, et al. Is progesterone elevation on the day of human chorionic gonado-trophin administration associated with the probability of pregnancy in in vitro fertilit-zation? A systematic review and meta-anal-ysis. Hum Reprod Update 2007;13:343–54.

11. Kolibianakis EM, Venetis CA, Tarlatzis BC. Role of the endocrine profile for the achievement of pregnancy with IVF. Re-prod Biomed Online 2009;18:37–43.

Abigail Delaney, MD, is a chief resident at the Uni-versity of Nebraska Medical Center in Omaha, Neb. Email: [email protected]

Jani R. Jensen, MD, is a consultant in the Division of Reproductive Endocrinology and Infertility at Mayo Clinic in Rochester, Minn.

Email: [email protected]

Dean E. Morbeck, PhD, is IVF Laboratory director at Mayo Clinic in Rochester, Minn.

Email: [email protected]

Disclosure: The authors have nothing to disclose.

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As clinical chemists, we play a major role in evaluating and implementing new methods and analyzers. During fel-lowship training, we become

well-versed in the method evaluation pro-cess, mainly from a theoretical point of view. Written guidelines, such as those published by the Clinical and Laboratory Standards Institute (CLSI), describe the technical com-ponents of a method evaluation in detail, including imprecision, method comparison, linearity, analytical sensitivity, carry-over and verification of reference intervals. But what happens after the decision has been made to purchase a new analyzer? This process is much less well-defined and lacks writ-ten guidelines. Furthermore, trainees may not get much exposure to this more practi-cal side of laboratory operations. The flow chart presented here outlines these less well- documented steps, from the time the deci-sion is made to purchase an analyzer until the beginning of patient testing.

Going Step-by-StepFirst, a team must champion the imple-mentation. Ideally, members would include laboratory bench, senior technical, and laboratory information system (LIS) staff. The team should assume primary respon-sibility for managing the project, including communicating with other departments within the hospital, as well as with external contacts, to facilitate a smooth transition. The team also should plan both a realistic and ideal “go-live” date for implementa-tion, taking into account the needs of facili-ties management, information technology (IT), and laboratory operations.

Each stakeholder has specific needs that the team should take into account. Facili-ties management needs to be advised of the physical and environmental requirements for the new instrument. Changes may be re-quired to the existing laboratory infrastruc-ture, such as electrical and water. Larger-scale renovations may even be necessary. How the instrument will be delivered is a consider-ation, too. For example, is the service elevator large enough to accommodate the analyzer?

The IT department needs to be advised of changes required for specific tests that are being moved to the new analyzer and of any new tests being added to the existing menu. For example, the following would affect the LIS: changes to reference interval values, cut off values, critical values, and interpretative comments. These changes also will influ-ence how results are reported in electronic medical records, so it is important to com-municate and collaborate with the staff in-volved in making these changes.

Within the laboratory, consideration should be given to whether additional staff will be needed, especially if the instrument adds completely new tests to the lab’s menu. Staff running the new analyzer also will re-quire comprehensive, hands-on training, either on-site or off-site. Off-site training adds time and expense to the project.

Another consideration is test volume. The team should estimate the new work-load so that sufficient reagents can be or-dered, as well as check on whether licensing is needed for any new tests.

Planning for QC and PTAnother step is setting up appropriate quality control (QC) procedures. The team should decide which QC material the lab will use and set quality goals for each method. These decisions should be based on the method evaluation data, clinical need, and published requirements, such as those defined by Clini-cal Laboratory Improvement Amendments (CLIA) or other national programs.

An external quality assessment (EQA) or proficiency testing (PT) program is required for each test performed in the laboratory. The team should notify PT pro-viders of any changes in methodology and request PT surveys for new tests. For some analytes, PT is not available and an alter-native scheme must be developed, such as inter-lab comparison. As part of total qual-ity management within the laboratory, the team should prepare standard operating procedures for each new pre-analytical, an-alytical, and post-analytical process associ-ated with the new analyzer and tests. If an analyte will be measured on more than one instrument, inter-instrument comparisons also will be required.

Communicate!Finally, prior to the go-live date, labora-tory staff needs to communicate the im-pending changes to both internal and ex-ternal clients, including the date on which the changes will occur. Communications

should be planned well in advance so that there is ample time for client education about changes to reference ranges, cut off values, turnaround time, and new interpre-tive comments.

Celebrate Success When the analyzer and new tests are up and running, it is always a good idea to re-view what went well and what didn’t. And don’t forget to thank committee members for all their hard work! CLN

Julie Shaw, PhD, is a clinical biochemist at The Ottawa Hospital in Ottawa, Ontario, Canada and an assistant professor in the Department of Pathology and Labora-

tory Medicine at the University of Ottawa. Email: [email protected].

For more information on AACC’s SYCL, visit www.aacc.org/members.

Introducing SYCL SnapShotsWelcome to SYCL SnapShots, a new quarterly column in CLN describing essential skills and practices for effective laboratory management. Here, members of AACC’s Society for Young Clinical Laboratorians (SYCL) will present a snapshot of a topic, such as business basics, data analysis and statistics, or online tools. We hope CLN readers will find this new column valuable and we welcome your feedback.

Christopher McCudden, PhD SYCL Chair The Ottawa Hospital Ottawa, Ontario, CanadaEmail: [email protected]

Practical Considerations for Implementing a New Lab AnalyzerBY JULIE SHAW, PHD

Practical Steps for Implementing a New AnalyzerFull Method Evaluation

Decision to Purchase

Create Implementation Committee

Contact IT

Space Requirements Staffing RequirementsHire New Staff?

TrainingScheduling

SuppliesOrdering

Storage/Inventory

Lab license

Communications

Quality ControlMaterialLevels

FrequencyQuality Goals

EQAOrdered or Alternative

Scheme Plan

Electronic Patient Record

Water Requirements

Electrical Requirements

Contact Facilities/ Engineering

Within-lab Organization

Implementation

SOPsPre-analytical

AnalyticalPost-analytical

LIS ConnectivityReference Intervals

Critical ValuesComments

Reflex TestingAutoverification

Delta ChecksTemperature/Humidity

Requirements

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CMS Launches Pay-for- Performance Initiatives

In October, the Centers for Medicare and Medicaid Services (CMS) launched two

initiatives that aim to reward hospitals for outcomes and quality: the Hospital Value-Based Purchasing Program and the Hos-pitals Readmissions Reductions Program. Created under the Affordable Care Act, both programs aim to save Medicare mon-ey and boost quality.

Under the value-based purchasing program, Medicare will withhold 1% of regular reimbursements to acute care hospitals and redistribute the resulting approximately $850 million based on certain performance criteria. Taken from money that Medicare otherwise would have spent, the size of the fund will gradu-ally increase over time, resulting in a shift

from payments based on volume to pay-ments based on performance, according to CMS.

The quality metrics include: ensuring that patients who may have had a heart attack receive care within 90 minutes; providing care within a 24-hour window to surgery patients to prevent blood clots; communicating discharge instructions to heart failure patients; and the results of patient satisfaction surveys. The better a hospital does on its quality measures, the greater its reward.

The second pay-for-performance pro-gram focuses on hospital readmissions. Similar to the value-based purchasing program, the Hospitals Readmissions Re-ductions Program withholds up to 1% of reimbursements, but only for hospitals that show too many readmissions within 30 days of discharge for heart attack, heart failure, and pneumonia. CMS plans to add

other conditions to the list in the future. Some experts have estimated that nearly two-thirds of hospitals could face penalties of more than $100,000, with hospitals over-all losing about $280 million in reimburse-ment this year.

Penalties for readmissions will increase over time, from 1% this year, to 2% next year, and 3% in 2015. According to CMS, about 2 million Medicare beneficiaries treated in hospitals return within 30 days annually, costing more than $17 billion.

More information about the programs is available from www.healthcare.gov.

ACLU Pushing for Supreme Court Review of Gene Patents Case

The American Civil Liberties Union (ACLU) and the Public Patent Foun-

dation are asking the U.S. Supreme Court to again review and invalidate BRCA1 and BRCA2 patents held by Myriad Genetics and the University of Utah Research Foun-dation.

In May 2009, The College of American Pathologists and the Association for Mo-lecular Pathology, among others, joined an ACLU lawsuit challenging the patents used for breast cancer risk testing.

On March 29, 2010 a New York federal court ruled that the patents on the BRCA1 and BRCA2 genes were invalid. The U.S. Court of Appeals for the Federal Circuit heard Myriad’s appeal of that ruling in April 2011. In July 2011, the appeals court ruled that companies can obtain patents on the genes but cannot patent methods to compare those gene sequences.

Finally, in March 2012, the U.S. Supreme Court vacated the decision of the appeals court and instructed the court to reconsid-er the case in light of Mayo v. Prometheus, a Supreme Court decision unanimously

invalidating patents on methods for evalu-ating a patient’s response to a drug.

When ACLU lawyers argued before the U.S. District Court judge in New York, they said that medical research was being held back by the BRCA1 and BRCA2 patents and that these genes were “an ancient secret of nature.” Attorneys representing Myriad Genetics and the University of Utah Re-search Foundation countered that a ruling making these patents invalid would “wreck the foundation of the entire biotechnology industry.”

More information about the case is available from www.aclu.org/brca.

House Passes CLIA Referral Legislation

The House of Representatives has passed an AACC-endorsed bill that could ease

one of labs’ biggest problems with pro-ficiency testing (PT) programs. The bill, H.R.6118, “Taking Essential Steps for Test-ing Act,” gives the Centers for Medicare and Medicaid Services (CMS) greater flexibility on what penalties to impose on a labora-tory that sends a PT specimen to an outside laboratory.

Under current law, laboratories that re-fer PT specimens to an outside laboratory lose their CLIA certificate for at least 1 year, even if the specimen was not referred to in-tentionally cheat. Since many labs have pol-icies that automatically refer certain speci-mens to another lab, the statute has been a cause for concern for many years.

The House passed the bill just before both houses of Congress recessed, but af-ter the elections, the Senate could vote on companion legislation during the lame duck session that begins November 13.

The bill is available from the THOMAS website, http://thomas.loc.gov.

R E G U L AT O R Y

P R O F I L E SP R O F I L E S



Illumina Buys Genomics-Based Diagnostics Company BlueGnome

Illumina purchased genomics-based di-agnostics company BlueGnome for an

undisclosed sum. BlueGnome’s main offer-ings include 24sure, a preimplantation ge-netic screening test that shows the potential to improve in vitro fertilization (IVF) suc-cess rates, and CytoChip, a first-line cytoge-netic test for genetic abnormalities associ-ated with developmental delay or complex leukemias. The company’s focus on cytoge-netics and IVF screening solutions supports Illumina’s goal to become a leading pro-vider in these areas. On BlueGnome’s side, president and CEO, Nick Haan, said, “The throughput and data quality of Illumina’s sequencers enable us to consider revolu-tionary new approaches to genetic testing.”

Beckman Coulter to Acquire IRIS International

Beckman Coulter, Inc., a wholly-owned subsidiary of Danaher Corporation,

announced a definitive merger agreement with IRIS International, Inc. Beckman Coulter will acquire IRIS, which produces automatic in-vitro diagnostics systems, for approximately $378 million at $19.50 per share. “IRIS provides an excellent comple-ment to Beckman Coulter’s core business, as we continue to focus on our strategy of serving the core hospital laboratory,” said Tom Joyce, Beckman Coulter’s president and Danaher’s EVP. With Beckman Coul-ter’s strong commercial infrastructure, IRIS will be able to expand the reach of its automated and semi-automated uri-nalysis products. Beckman Coulter might also benefit from IRIS’s unique cell imag-ing technology, which could potentially be used to improve Beckman’s hematol-ogy product lines. The deal between the two companies is expected to close in the fourth quarter.

Wako Life Sciences Joins Ranks of Diagnostics Companies

The former diagnostics division of Wako Chemicals USA, Wako Life Sciences,

has become a fully incorporated diagnos-tics company focused on developing and commercializing microfluidic test systems for the immunoassay and molecular diag-nostic markets. The new company head-quarters are in Mountain View, Calif., while its research and development facilities and commercial operations are in both Moun-tain View and Richmond, Va.

UPMC Enters Data Warehouse Initiative with Oracle, IBM, Others

The University of Pittsburgh Medical Center (UPMC) has made a 5-year,

$100 million investment to create a data warehouse with Oracle, IBM, Informatica,

and dbMotion that will focus on person-alized medicine. The data warehouse will include clinical, financial, administrative, genomic, and other hard-to-analyze in-formation from more than 200 sources across UPMC, UPMC Health Plan, and other labs and pharmacies. This infor-mation will be processed using advanced analytic and predictive modeling applica-tions to improve patient outcomes and reduce healthcare costs. “UPMC, with the help of the Carnegie Mellon Software Engineering Institute, has methodically studied best practices in analytics both inside and outside of health care,” said Lisa Khorey, UPMC vice president of en-terprise systems and data management. With this current initiative, she added, UPMC aims to use what the organization has learned to move towards a personal-ized medicine model.

Life Technologies and Bristol-Myers Collaborate to Develop Co-Diagnostics

Life Technologies and Bristol-Myers Squibb have entered a master devel-

opment agreement that creates a long-term partnership to develop companion diagnostics. Life Technologies president of medical sciences Ronnie Andrews said, “As more and more targeted drugs come onto the market in the next decade, there will be a growing need for diagnostics that can help predict which patients will benefit from which drugs.” With its broad portfo-lio of genetic and proteomic analysis plat-forms, Life Technologies will be able to give a pharmaceutical company such as Bristol-Myers a “flexible, cost-effective means to manage the evolution of the companion diagnostic assay through the drug devel-opment process,” added Andrews. The two firms’ first project together will focus on oncology, a specialty in which the demand for companion diagnostics is predicted to rise due to the hundreds of oncology drugs currently in clinical trials.

PrimeraDx Awarded Grant to Develop DLBCL Assay

The National Cancer Institute-sponsored Innovative Molecular Analysis Tech-

nologies Program has awarded PrimeraDx a grant to develop an assay to detect dif-fuse large B-cell lymphoma (DLBCL) sub-groups. The assay will be designed for use on PrimeraDx’s ICEPlex automated real-time PCR platform, and will test formalin-fixed, paraffin-embedded specimens. This assay has the potential to improve upon gene-expression profiling (GEP) with snap frozen tissues, the current method for clas-sifying DLBCL subtype cells-of-origin. GEP is not practical in many lymphoma cases because it requires frozen tissue, a short-coming that PrimeraDx’s novel approach remedies.

Trovagene Enters Licensing Agreement with Quest Diagnostics

Trovagene finalized a deal with Quest Diagnostics that grants Quest a non-

exclusive license to incorporate nucleo-phosmin protein (NPM1) into research and clinical testing services related to acute myelogenous leukemia (AML). According to Trovagene chief technology officer Char-lie Rodi, PhD, this will help the company expand patient access to the NPM1 marker on a global scale. “Physicians need accurate tools to assess prognosis, select therapies and evaluate for bone marrow transplant,” he said. “Use of this marker can help phy-sicians more effectively treat patients with AML.” Currently, chromosome analysis is the most common method that provides guidance for physicians treating AML pa-tients. Because the method is effective in

only about half of AML cases, screening for NPM1 mutations could become a valuable addition to the array of available AML co-diagnostics.

Sysmex America Relocates Headquarters

Sysmex America, the U.S. subsidiary of Japanese company Sysmex Corpora-

tion, has relocated its corporate offices to a new facility in Lincolnshire, Ill. This site will serve as headquarters for the Ameri-cas along with the company’s logistics op-erations center in Buffalo Grove, Ill., and its Mundelein, Ill., reagent plant. “Our new building supports the infrastructure that our continued growth requires, as well as accommodates for future expansion,” said John Kershaw, president and CEO of Sys-mex America.


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AACC Elects New OfficersSteven Wong to Serve as President in 2014

AACC members elected Steven Wong, PhD, DABCC, FACB, to serve as President of the association in 2014, an-nounced AACC Secretary Elizabeth Frank, PhD. Also newly elected are Dennis Dietzen, PhD, DABCC, FACB, and Corinne Fantz, PhD, DABCC, FACB, to serve as members of the Board of Directors, as well as Michael Bennett, PhD, DABCC, FACB, as Treasurer. Four individuals were elected

to serve on the 2013 Nominating Committee: Shannon Haymond, PhD, DABCC; Loralie Langman, PhD, DABCC, FACB; Stacy Melanson, MD, PhD; and M. Laura Parnas, PhD, DABCC, FACB.

Wong takes his place as AACC’s 65th President, having been active in the association since 1980. He is professor of pathology at Wake Forest University School of Medicine and director of clinical chemistry and toxicology in the core laboratory at Wake Forest Baptist Medical Center in Winston-Salem, N.C., where he also is a member of the Point of Care Testing Committee, and Co-Director of the Clinical and Translational Mass Spectrometry Center.

Wong’s service to AACC includes time as a member on the Board of Directors, chair of three AACC divisions and the North Carolina Local Section, and a member of the organizing committee for a proteomics conference.

During his presidency, Wong plans to focus on collaborating with other medical associations, as well as government agencies such as the National Institutes of Health, to advance personalized medicine.


HMGB-1 Protein Best Predictor of CF Complications

In a longitudinal study of patients with cystic fibrosis (CF), researchers at the

University of Utah found that among the sputum biomarkers measured, only high mobility group box-1 (HMGB-1) pro-tein was associated with future acute pul-monary exacerbations (APE) and time to lung transplantation or death (PLoS One 2012;7:e42748). In comparison to percent predicted forced expiratory volume in 1 second (FEV1%) and all other biomarkers alone or in combination, sputum HMGB-1 measurement was a better predictor of sub-sequent APE and time-to-first APE.

The investigators conducted the study under the premise that biomarkers that predict clinical outcomes might also iden-tify causal mechanisms for airway disease in CF, help determine quickly the efficacy of new therapies, and distinguish patients most in need of urgent interventions.

The study involved 97 adult CF pa-tients recruited between 2004–2007 and followed a median of 5.9 years. In addition to HMGB-1 the researchers measured nu-merous other sputum biomarkers, includ-ing granulocyte macrophage colony stimu-lating factor (GM-CSF), interleukin-1 , 2, 5, 6, 8, 10, 12p40, 13, and 17, and tumor necrosis factor- , among others.

The authors conducted five different statistical analyses, including biomarker measurements and concurrent clinical status, biomarker behavior with change in patient status from stable to APE, relation-ship of biomarkers with APE-associated clinical changes, prediction of future APE, and HMGB-1 as an independent predic-tor of lung transplantation or death. After all these analyses, HMGB-1 proved to be the key biomarker; however, at APE onset, GM-CSF was significantly associated with APE-associated declines in lung function.

HDL-C SNP Carriers Not At Reduced Risk for MI

Alarge international consortium of re-searchers found that polymorphisms

related to plasma LDL cholesterol (LDL-C) were consistently associated with risk of myocardial infarction (MI), whereas the same association did not hold for variants related to plasma HDL cholesterol (HDL-C) (Lancet 2012;380:572–80). The findings suggest that some genetic mechanisms that raise HDL-C do not lower risk of MI; hence lifestyle or pharmaceutical interventions that raise plasma HDL-C can’t be assumed to lower risk of MI.

In a case-control design, the investiga-tors first tested lipid-associated SNPs in-dividually for association with risk of MI. Next, they tested two instruments, a single SNP, LIPG Asn396Ser, which is related to plasma HDL-C, and a genetic score con-sisting of 14 common SNPs exclusively

associated with HDL-C. They tested LIPGAsn396Ser in 20,913 MI cases and 95,407 controls from several different studies, and the genetic score in 12,482 MI cases and 41,331 controls. In addition, they tested a genetic score of 13 common SNPs associ-ated exclusively with LDL-C.

The authors found that in comparison to non-carriers, subjects who carried the LIPG 396Ser allele had higher HDL-C but similar levels of other lipid and non-lipid risk factors for MI. The investigators esti-mated that carrying this allele should de-crease risk of MI by 13%, but found it did not, as individuals with this allele had an odds ratio of 0.99. Observational epidemi-ology studies indicate that a 1 standard de-viation (SD) increase in HDL-C is associ-ated with reduced risk of MI; however, the researchers found that a 1 SD increase in HDL-C due to genetic score was not associ-ated with risk of MI. In contrast, estimates from observational epidemiology suggest that a 1 SD increase in LDL-C is associated with an increased risk of MI, with an odds ratio of 1.54. This risk concurred with the risk from the authors’ genetic score.

Preoperative Hyponatremia Predicts Postoperative Complications

Preoperative hyponatremia, even to a mild degree, is common and predicts

postoperative morbidity and mortality, even in relatively healthy patients, and in those undergoing nonemergency surgery (Arch Intern Med doi:10.1001/archin-ternmed.2012.3992). The findings suggest that even mild changes in serum sodium are not inconsequential and should not be ignored. In addition, whenever possible, the underlying cause of hyponatremia should be uncovered.

The authors assembled a cohort of pa-tients from the American College of Sur-geons National Surgical Quality Improve-ment Program. In all, they found data from 964,263 patients who were at least 18 years old, underwent any major surgery between 2005–2010, and in whom preoperative so-dium measurements had been recorded. Of these, 75,423 (7.8%) had hyponatremia, defined as sodium <135 mEq/L. In com-parison to patients with normal baseline sodium levels, defined as 135–144 mEq/L, those with hyponatremia had an adjusted odds ratio of 1.59 for 30-day mortality, 1.21 for perioperative major coronary events, 1.24 for wound infections, and 1.17 for pneumonia. The excess risk was present even in patients with mild hyponatremia, defined as 130–134 mEq/L. After control-ling for all the covariates to account for dif-ferences in case mix, the investigators also found hyponatremia to be associated with a median 1 day longer hospitalization.

The researchers noted that contro-versy exists as to whether hyponatremia is a marker or a mediator of mortality and other adverse events, and called for further

studies to determine whether correcting the condition preoperatively will mitigate risks.

Elevated RF Confers Long-term Risk of RA in Healthy Individuals

Healthy individuals in a general popula-tion with elevated rheumatoid factor

(RF) have up to 26-fold greater long-term risk of rheumatoid arthritis (RA), and up to 32% 10-year absolute risk of RA (BMJ 2012;345:e5244). These findings could lead to revision of RA clinical practice guide-lines to suggest that depending on RF test results, early referral to a rheumatologist or arthritis clinic might be warranted.

This prospective cohort study involved 9,712 adults without RA at enrollment. Subjects provided blood samples between 1981–1983, which were frozen at -20°C. The participants were followed until 2010, when RF concentrations were measured from the 1981–1983 samples. During 187,654 person years of follow-up, 183 in-dividuals developed RA. Median age at di-agnosis was 70 years and the median time from providing a blood sample to develop-ing RA was 15 years for those with RF lev-els <25 IU/mL, 12 years for those with RF

concentrations 25–50 IU/mL, and 7 years for those with RF levels of either 50.1– 100 IU/mL or >100 IU/mL.

The cumulative incidence of RA in-creased with increasing RF levels. In compar-ison to individuals with RF levels <25 IU/mL, multivariate adjusted hazard ratios for RA were 3.6 for RF levels 25–50 IU/mL, 6.0 for RF concentrations 50.1–100 IU/mL, and 26 for RF levels >100. The highest absolute 10-year risk of RA was found in women 50–69 years old who smoked and had RF concen-trations >100 IU/mL. The lowest risk was in men at least 70 years old with RF levels <25 IU/mL, irrespective of smoking status.

D I A G N O S T I C


2013 AACC Annual Meeting

July 28– August 1

Houston, Texas



BD Receives Clearance For Rapid Flu Test

FDA cleared the BD Diagnostics BD Veritor System for Rapid Detection of

Flu A+B, for use in clinical settings. The kit is designed for testing liquid specimens ob-tained via nasopharyngeal wash, aspirate, or swab in transport media. The assay uses BD’s proprietary advanced particle and adaptive read technologies, which increase the test’s sensitivity and reduce false posi-tives, respectively.

FDA Clears RSV Test

BD Diagnostics received clearance from FDA for a respiratory syncytial virus

(RSV) test designed for use on the BD Veri-tor System. This is the third FDA-cleared test for this platform. Like BD’s Rapid Detection of Flu A+B for the BD Veritor System, Rapid Detection of RSV tests na-sopharyngeal wash, aspirate, and swab in transport media specimens. It also couples proprietary advanced particle and adaptive read technologies with a digital display to provide objective, easy-to-read test results.

Roche’s CoaguChek XS Plus Granted CLIA Waiver

FDA granted CLIA-waived status to Roche’s CoaguChek XS Plus system,

a point-of-care anticoagulation monitor that helps hospital staff manage prothrom-bin time/international normalized ratio (PT/INR) testing. Quality controls built into the system ensure the accuracy of PT/INR results, while optional liquid qual-ity controls accommodate facilities where policy requires external quality control measures. The system’s connectivity capa-bilities also help healthcare professionals streamline organization and the regulatory compliance process by allowing them to connect and transfer data to IT solutions.

HIV-1 Viral Load Test Approved

Roche received FDA approval for an HIV-1 test that uses the company’s pro-

prietary dual-target approach to improve physicians’ viral load monitoring capabilities. The dual-target approach, as its name sug-gests, targets two highly conserved regions of the HIV-1 genome and avoids regions that are current drug targets. This strategy ensures accuracy even when mutations are present in the viral genome, leading to more reliable test results. The test also combines the High Pure System Viral Nucleic Acid Kit with the COBAS TaqMan 48 Analyzer to provide manual specimen preparation, and automat-ed amplification and detection.

FDA Approves Group A Strep Test

FDA has cleared Meridian Bioscience’s diagnostic test for Group A Streptococ-

cus on the Illumigene platform. The Group A Strep bacterium causes a number of dif-ferent illnesses, including pharyngitis, one of the most common reasons for consulta-tions with primary care physicians. Merid-ian’s test diagnoses pharyngitis by detecting Streptococcus pyogenes in throat samples us-ing loop-mediated isothermal DNA ampli-cation (LAMP) technology. This procedure takes less than an hour, and has the poten-

tial to improve upon the accuracy and sen-sitivity of traditional pharyngitis diagnos-tics such as rapid antigen testing and throat swab culture.

Focus Diagnostics Receives Clearance for Flu, RSV Test

The Focus Diagnostics Simplexa Flu A/B & RSV Direct test on the 3M Integrated

Cycler received FDA clearance and CLIA moderate-complexity categorization. The test qualitatively detects and differentiates RNA of influenza A and B viruses and the

respiratory syncytial virus in nasopharyn-geal swabs without the requirement for ex-tracting nucleic acids.

Respiratory Virus Panel Cleared

GenMark Diagnostics received 510(k) clearance from FDA for its eSensor

Respiratory Virus Panel (RVP). Intended for use on GenMark’s XT-8 system, the test can concurrently detect and distinguish be-tween 14 major viruses that cause influenza-like illness, including rhinoviruses, enterovi-ruses, and clinically relevant adenoviruses.

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