HoSt FAQs

FAQs for hormones standardization programs

What makes HoSt unique?

CDC's HoSt is unique because it uses unmodified, high-quality serum samples for evaluating analytical bias and precision. This allows analytical performance assessment with sera similar to those used in patient care settings. The use of this type of sera is required because modified sera, such as those that are pooled or otherwise modified, can introduce so-called "matrix effects," which can produce incorrect measurement results and conclusions about the accuracy of a test, though the test would be considered accurate when using patient samples.

How can laboratories collaborate with CDC to assess the analytical accuracy and precision of their diagnostic tests?

Manufacturers of diagnostic products and lab-developed tests can contact CDC's Clinical Standardization Programs to obtain information about available options to address their specific needs. The two commonly used options are:

• Manufacturers and laboratories can participate in Phase 1 and obtain up to 120 different samples with reference values assigned by the reference measurement procedures. These samples can be used to assess and optimize the analytical performance of their laboratory methods. The CDC Clinical Standardization Program Team can assist with these activities.

• Manufacturers and laboratories can enroll in Phase 2 and obtain 10 samples quarterly as described above. Only participation in Phase 2 can lead to certification. Only certified participants are considered standardized by the CDC Clinical Standardization Programs.

Phase 1 and Phase 2 activities are independent from each other.

How do laboratories obtain CDC certification?

Certification can be obtained only by enrolling in HoSt-Phase 2. Manufacturers of diagnostic products and lab-developed tests receive four blinded quarterly challenges that include 10 single-donor samples each, over the course of a year. Results from each blinded challenge are used to perform bias and imprecision assessments of each assay. Certifications are issued to assays that meet performance criteria. Certification evaluation is conducted for the first time after 4 quarters (1 year) of participation and then quarterly using four previous consecutive quarters. Certification is valid for one quarter. Certified laboratories will be added, with permission, to CDC's estradiol or testosterone certified laboratories list.

What does it mean to be certified?

Participants that are certified have analyzed HoSt samples for four consecutive quarters (40 samples), and their measurement data have met certain analytical performance criteria after evaluation using standard protocols such as those describe in protocol CLSI EP9.

Certification criteria differ among programs. Please contact CDC CSP for information on specific programs. In most programs provided by CDC's Clinical Standardization Programs, the average difference ('mean bias') between the participant method and the CDC RMP is calculated using data from 40 samples. This mean bias is compared to an allowable bias suggested by clinical and public health stakeholders. If the mean bias is within these allowable limits, the participant method being certified for its accuracy. The mean bias described here can be considered an estimate on how well the participant method is calibrated. It may not provide information on other factors that can affect the accuracy of measurements obtained in individual samples.

What information is included in the list of certified participants?

The lists of estradiol and testosterone certified participants includes the following information: date certified, name/type of assay, reportable range, proportion of individual samples meeting criteria, contact details, and the date of certification. Proportion of samples meeting bias criteria is listed to help end-users make knowledgeable decisions regarding which assay or laboratory to use for testing purposes.

What is the difference between mean bias and sample bias?

A laboratory method can be well calibrated but may produce inaccurate results on individual samples. Mean bias is the average bias of all samples used in the certification phase (generally 40 samples). This mean bias provides information on how well a laboratory method is calibrated and is used as one of the certification criteria. The sample bias is the bias of an individual sample compared to the reference value. The percentage of individual samples meeting analytical performance criteria for bias can be found on the lists of estradiol and testosterone certified participants. CDC started listing this information in 2017.

What does it mean when participants are no longer included on the list of certified participants?

Being listed as certified participant is voluntary. Participants may chose not to be listed. Participation in CDC's Clinical Standardization Programs is also voluntary, and participants may chose to discontinue in Phase 2. CDC's Clinical Standardization Programs provides one list with currently certified participants that agreed to be listed, and a separate list with participants that either no longer participate or chose to be listed no longer.

How often are certified assays updated on the website?

The list is updated quarterly. Once participants have completed four consecutive quarters, their results will be evaluated and those participants meeting certification criteria are listed on the website.

What is the goal of HoSt certification?

The goal of certification through HoSt is to ensure that tests for steroid hormones, such as total testosterone and estradiol, produce accurate results. This is achieved by standardizing tests at the manufacturer level. In this way, laboratories do not need to conduct standardization activities themselves. Furthermore, laboratories using certified assays also can use reference intervals and clinical decision points generated with certified assays. In examples, laboratories using assays certified by CDC HoSt for testosterone, can use clinical decision point described in the Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.

Why is the certification process important?

The certification process ensures that the method in question is accurate over time. Many clinical laboratories rely on test manufacturers to maintain certified methods.

What is involved in the certification process?

A manufacturer or clinical laboratory that wants to be involved in the certification process should contact Standardization@cdc.gov and obtain the testosterone and estradiol protocols.

Can more than one test be certified with the same set of samples?

To be certified, each test must be enrolled separately and receive its own set of samples.

How long will the certification process take from sending samples to receiving certification?

After meeting acceptance analytical performance for four consecutive quarters, a participant is certified. The certification is valid for one year. After four consecutive quarters, participants are evaluated quarterly for certification.

Does HoSt have a protocol for recertification?

Yes. Participants are encouraged to re-enroll in the program upon receiving certification to prevent gaps in certification status. See protocol for further information.

What is the best way to verify that my analytical system has low bias before embarking on a full certification effort?

The best way to verify low bias in an assessment is to perform a comparison with the Hormone Reference Laboratory using the 40 patient samples provided in Phase 1 of the program. Phase 1 can be used to assess bias and recalibrate methods as necessary before beginning Phase 2.

See estradiol and testosterone program protocols for more details about Phase 1 and Phase 2.

Should my laboratory send in standards or calibrators to be analyzed by the reference method first?

Reference measurement services are offered through HoSt, but sending standards to be analyzed by the reference method before enrolling it is not necessary. For more information on reference measurement services, contact Standardization@cdc.gov.

Can CDC's HoSt assign values to samples provided by my laboratory?

CDC works on meeting these requests, but such services are subject to availability of resources. For more information on reference measurement services, contact Standardization@cdc.gov.

If my laboratory has "out-of-control" runs during analysis of certification samples, or if the samples analyzed include "out-of-control" values, can I choose not to report the unusual values?

Laboratories should apply their rules and policies for reporting results. If you have "out-of-control" runs during the certification process, you should investigate the reasons for these deviations before you re-analyze certification samples.

What materials are used in the CDC standardization programs?

Reference materials used in the programs are prepared from unaltered single-donor human serum, in accordance with CLSI guideline C37-A (Preparation and validation of commutable frozen human serum pools as secondary reference materials for cholesterol measurement procedures; approved guideline).

The HoSt Program reference materials are stored and maintained frozen, at or below -70°C. Shipments of samples to regions that do not accept dry ice can be arranged. On arrival, the frozen reference material must be immediately transferred to a freezer for storage at -70°C.

Is there a yearly deadline for enrollment?

Participants may enroll in the program at any time and may begin receiving samples during any of the 4 quarterly shipments (February, May, August, and November).

HoSt criteria

*Criteria included in performance report but not currently used for certification ** 80% of reported samples must meet bias criteria for Estradiol certification