generalist – Page 31

Failure is Always an Option

I had some fun this April Fool’s Day and sent some emails out that stated we failed some CAP surveys. I know I’m evil but you have to have some fun sometimes! The reactions were interesting in that everyone deals with failure differently. Show me someone who has never failed and I’ll show you someone who won’t know how to react once they do. It is inevitable. We try to never experience it but we will and it is how you react that sets people apart.

I am proud and speak of my failures regularly because it gives people strength knowing that they are not alone. In my career I have been involved in a total hospital failure and had to work my way back up the ladder. It is through these failures that we learn the most about ourselves and about situations. When I was just out of school I used to think that experience wasn’t that important. I thought, “I’ve learned what I need to know in school, I should be a supervisor NOW!” I am in the second half of the first 10 years of my career and have learned that every situation brings with it experience that becomes knowledge. That knowledge will carry me into the second and third decades of my career. Both the successes and failures will help me as I move forward.

Experience is gained through those situations and it is up to the people involved to either take it with them or forget about it and be vulnerable to repeat them. As leaders we are sometimes under pressure to work or move forward with options that may not be our choices, but we must get our staff to buy in and perform. These directives usually given from a few pay grades above should be followed so that if you do fail you can show that you followed their directives. You do not want to be seen as someone who is resistant to change or someone who will be an obstacle. This will just get you more headaches and possibly affect your advancement in the future. Having said that always state your concerns as well as present ideas that may be a better option. You do not want to be silent when it matters most.

I have always learned more from my failures than I have from my successes. During an interview a CEO once told me, “You want to make your big mistakes early in your career because the higher you get the less forgiving people are of the big ones.” We make our mistakes during a constant search to be the so-called “polished professional.” When we get to the higher pay grades we should be able to see a failure coming a mile away and be able to safely get out of the way. Successes come with great planning and a dump truck full of experiences. Remember, failure is always an option.

–Matthew Herasuta, MBA, MLS(ASCP)CM is a medical laboratory scientist who works as a generalist and serves as the Blood Bank and General Supervisor for the regional Euclid Hospital in Cleveland, OH.

Direct To Consumer Testing: Wave of the Future?

Direct to consumer (DTC) testing is one of the fastest growing industries on the internet, and if laboratories are not careful, we’re going to be blind-sided by it. I wanted to know how this works because in general the websites for this testing have nothing whatsoever on them about the lab. I searched for lab information – accreditation, etc – and found nothing. What I found was that most of these sites are essentially online middlemen between the consumer and the labs – allowing access to lab testing and bypassing the doctor. I decided to do an experiment and see just how easy it was.

I went online and found a DTC company and ordered tests. I skipped their specials, “test of the month” was a complete thyroid panel, and settled for their most popular, most ordered test. It is actually a group of tests which includes a CBC with differential and a chemistry panel for a total of 27 tests plus six calculated values (eGFR, HDL/total cholesterol ratio, etc). The complete test cost me $97.00 plus tax. I can tell you that those tests run at my institution would cost well over $2500.00, and even at a big reference lab, the best price I could get was about $425.00.

It was when I placed my order that any mention of a lab came into the process. Before I could place the order, I had to make sure there was a LabCorp near me. I then went back to the website and printed the company’s requisition for the test and took it with me to a LabCorp draw station. They took the requisition, checked it against a photo ID, collected the appropriate blood samples and sent me on my way. Three days later I received an email from the online company that my results were available. I logged on, and it was just that easy. There were all my test results with appropriate reference intervals and flags. If I want my physician to have a copy, I can have them sent or print them and take them with me.

Amazingly, this is incredibly easy to do, although I suppose you would have to know enough to know what tests to order, or be told what to order by your physician. But I now have the ability to order my own tests, and at significantly less cost than the average hospital or reference lab. If doctors begin telling their patients just what tests to get run and then to bring them the results, this DTC testing will put hospital labs out of business, at least out of the outpatient lab business. There’s no way for a hospital lab to compete with this cost structure. Now all you need is a LabCorp interface to your hospital system and the test results go right back into the chart where the doctor ordered them and the hospital lab is totally outside the loop.

Of course, you will also have people just running tests on themselves after doing some online research, but they will still have to hook up with a doctor somewhere to explain abnormal lab results. I’ve already seen some of that – calls or emails from people off the street looking for explanations of results of metabolic testing. DTC is going to open many, many cans of worms, but it’s coming, nonetheless. I suppose there might be a role for the laboratory professional here, to help the consumer understand their lab results when they do them directly. And hospital labs will always be necessary for STAT and critical tests for inpatients. But the world is changing. We need to be ready for it.

-Patti Jones PhD, DABCC, FACB, is the Clinical Director of the Chemistry and Metabolic Disease Laboratories at Children’s Medical Center in Dallas, TX and a Professor of Pathology at University of Texas Southwestern Medical Center in Dallas.

Pediatric Reference Intervals

All laboratory professionals are aware of the importance of reference intervals (RI). Without appropriate reference intervals, a test result is just a number. A numeric result for any given analyte cannot be used to diagnose or monitor treatment of disease unless there is an accompanying reference interval indicating what amount of that analyte should normally be present. In pediatrics, that’s even more important because as an infant develops through childhood and into adulthood, his or her biochemistry changes, adapts and develops with him or her. Using an adult RI to interpret a test result from an infant or child is likely to result in misinterpretation of the test, including misdiagnosis of disease states. A good example would be using adult alkaline phosphatase RI to interpret the results of a teenage boy’s test during accelerated bone growth in puberty. His result will look pathological if interpreted using adult RI. Pediatric reference intervals (PRI) are age-related and often also gender-related intervals that must be used to interpret testing in the pediatric population.

Establishing reference intervals is problematic at the best of times because of the need to use 120 healthy individuals to establish them. In the pediatric population, especially in infancy, obtaining 120 healthy infants at each necessary time interval can be a daunting task. There are references available that present methods which allow the establishment of RI with smaller sample numbers (1,2). Also the CLSI document (2) allows the “validation” and “transfer” of current or literature RI, rather than complete “establishment” of RI in some cases. Validating a current reference interval can be done with as few as 20 samples in a correlation study. “Transferring” a reference interval also involves using a correlation study and bias evaluation to adapt or adjust a current RI for use with a new assay. Transferring can also be performed with 20 – 60 patient samples.

These techniques especially come in handy with the hardest PRI to establish, the hormones during puberty. During this time, the RI are not really related to the child’s age, but related to the child’s phase of development, or Tanner Stage. To establish a PRI for these hormones, the healthy child donating the blood sample must also have his/her Tanner Stage determined, usually by an Endocrinologist.

Another consideration when dealing with PRI is that although all pediatric institutions use PRI, not all PRI are the same, even when the same instrument is used. An informal poll of 9 pediatric institutions using the same instrument resulted in 9 different PRI for common analytes such as electrolytes. There is a need to harmonize PRI, as we harmonize test results, in order to allow non-pediatric institutions a set of PRI that they can use also.

Horn PS, Pesce AJ. Reference Intervals: a User’s Guide. AACC Press, Washington DC, 2005
Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory: Approved Guideline – Third ed. CLSI C28-A3

Harmonization

What does “harmony” mean to you? And how does it apply to lab testing?

One of the biggest problems that arise where lab testing is concerned is that tests run in two different labs will give you two different results unless the labs happen to be using the same equipment (and sometimes even then the results won’t match!) This is a huge problem for doctors of patients who use different laboratories for their testing or patients who move across the country and need to continue following lab test results. A prime example of this dilemma is the current state of T4 testing. The same CAP sample when analyzed using different assay methods for thyroid stimulating hormone (TSH) can yield results which range anywhere from 2.66 to 8.84 mIU/L. Although CAP samples are not always commutable with patient samples, thyroid testing on patients shows this same lack of harmony.

This example underscores the need for harmonization. In our increasingly small world, where nearly everyone will soon be using the electronic medical record, and all lab results on a patient will be in one place whether they were all performed at the same place or not, it will be paramount that the lab results for any given test can be compared. Efforts to date have successfully harmonized several important analytes, including creatinine (IDMS-creatinine), cholesterol and hemoglobin A1c. Efforts are on-going to harmonize vitamin D assays against the NIST standards. These harmonization efforts took a massive amount of coordination and work between the in vitro diagnostic industry, regulatory agencies and laboratory and clinical societies.

Laboratory professionals have long recognized this problem, and sought to inform non-laboratorians of the realities at every opportunity. Lack of comparable test results can lead to patient safety issues, including misdiagnoses and/or inappropriate treatment. Recently an international consortium has recognized the need for harmonization of all lab results and begun to work on the problem. Although this effort is just beginning and the road ahead is long until general test harmonization can occur, it is a road worth traveling.

Rising Cost of Send Out Tests

More and more in this day and age, the laboratory is encouraged to reduce costs and streamline operations by using available resources in the most effective and efficient manner possible. One of the areas of the lab that is increasingly becoming a problem when it comes to cost reduction is the send out area. Since most labs can now perform the vast majority of their testing on automated chemistry and hematology analyzers, tests that must be performed at reference laboratories are increasingly esoteric, manual, and/or molecular diagnostic tests. And those tests are expensive.

As an example, my own lab sent out about 10 chromosomal microarray (CMA) tests in 2008; that number increased to 400 CMA tests in 2011 and is on track to be 865 in 2013. At $1400.00 each, the cost to the lab increased from $14,000 to $1.2 million over that time period. And that’s just one relatively inexpensive molecular diagnostic test. Some of the gene sequencing tests can run between $5000, and $10,000 per test.

Labs are trying a multitude of different schemes in order to try to curb these send out test costs. One method that is fairly effective is to have a “gatekeeper” – a person or persons who review and must approve every test that leaves the lab that costs over a pre-set amount. This particular method is probably one of the best for controlling send out costs, but it requires time and commitment on the part of the gatekeeper, and a willingness to interact with physicians who have ordered the tests that may be less than happy than someone is questioning their order.

Another method used for send out cost control is to include some indication of the cost of the test in the computer system. When the test is ordered, the ordering provider is aware of the exact cost of the test. Some institutions are using a dollar sign system to implement this. For example “$” may mean that a test costs under $50 and “$$$$$” may indicate a test costing over $5000, with other levels in between these two.

A third method is to have a lab “formulary.” Any test found in the formulary can be ordered with no problems. Tests that are not included in the formulary must be approved by the lab before being ordered and sent out.

Whatever method a laboratory uses, it is clear that some means of regulating the rising send out costs is going to be necessary for all labs. Until molecular diagnostic tests become automated and routine, they will continue to be expensive.

-Patti Jones

Reference Intervals vs. Reference Change Values

If we didn’t use reference intervals (RI), how would we know whether a person is “normal” or not? Or more accurately, how would we know whether a lab test result indicated health or disease? Reference intervals have been around as long as lab tests and they help clinicians diagnose and monitor a patient’s disease state. .

Most RI are developed using a specific patient population and should be used only with that population. However, some RIs are “health-based,” such as cholesterol and vitamin D. Both these analytes have RI that indicate what amount of the analyte should be present in a healthy individual, not how much is present in your specific population of patients. In general, health-based RI can be utilized in all populations, as long as the analyte assays are commutable. Thus these type of RI are often more useful than population-based intervals.

But should we be using reference intervals at all? One problem with population-based RI is that any given individual’s values may span a range that covers only part of the population RI due to biological variability. For example, an individual’s creatinine may be 0.6 – 0.9 mg/dL regularly. Since the RI for creatinine for his population is 0.4 – 1.4 mg/dL, a value of 1.2 mg/dL would not be flagged as be abnormal. However, 1.2 mg/dL may very well be an abnormal result for this individual We need to consider using reference change values (RCV) in addition to RI.

Reference change values are calculated values that are used to assess the significance of the difference between two measurements. Essentially, a RCV is the difference that must be exceeded between two sequential results for a change to be a significant change. The calculation requires knowledge of the imprecision of the analyte assay (CV_A) and the biological variation (CV_I) of the analyte. The formula for calculating RCV is: RCV=2^1/2 · Z · (CV_A² + CV_I²)^1/2 , where Z is the number of standard deviations for a given probability. Luckily, labs know the imprecision of their assays and there are tables available for biological variation.

It’s very likely that neither RI nor RCV by itself is adequate for interpreting analyte results. Using both may be a better alternative, especially using RCV for monitoring disease progression or therapeutic efficacy. Flagging sequential values that exceed the RCV—and reporting this change—should be considered.

-Patti Jones

Who Regulates Laboratory Developed Tests?

A laboratory developed test (LDT) is any test that has been developed by an individual laboratory, often using instruments and/or reagents that have not been approved by the FDA for use as/in an in vitro diagnostic test. For example, measuring pH using a pH meter and pH calibrators from a scientific supply company is an LDT. So is performing a spun hematocrit, measuring acylcarnitines by tandem mass spectrometry, or performing newborn screening on dried blood spots. Even using an FDA-approved assay for samples or in a manner not specified by the manufacturer makes that assay an LDT. If you look around your lab, you may find that you’re performing an LDT without really thinking about it.

Who regulates these tests? The FDA regulates in vitro diagnostic testing, and LDTs fall under their purview. Until recently the FDA has used “enforcement discretion” and has essentially allowed CLIA regulations and CLIA oversight to ensure proper validation and monitoring of LDTs. CLIA regulation Subpart K, Section 493.1253 gives the specific parameters that must be properly validated in any non-FDA-approved assay. CLIA also regulates the proper usage and control of LDTs, just like any test performed in the laboratory. Is it necessary for LDTs to be regulated more highly than this?

In June of 2010 the FDA announced its intention of taking a more active role in LDT regulation in the future. They also held a public meeting to discuss their increased oversight. All laboratories which perform LDTs will do well to monitor developments in this newly intended enforcement of the FDA’s role, and keep abreast of changes coming out in the regulatory environment for these tests.

-Patti Jones