The preanalytical phase – Past,present and future

In the brain to brain loop described by George Lundberg, ¹ the preanalytical phase is defined as all parts of the total testing process (TTP) that occur from the conception of the requirement for the test through obtaining of the sample, transport to the laboratory and sample preparation, to the point where the sample is ready for analysis. It is widely agreed that 60–70% of the errors that occur in laboratory medicine are attributable to the preanalytical phase. The term preanalytical phase first appeared in the literature in a paper by Statland and Winkel. ² Since then, interest in the preanalytical phase has grown: the frequency of the keyword ‘preanalytical’ in PubMed has increased to ∼160 occurrences in 2018. In fact, the term ‘laboratory error’ first occurred even earlier than this in 1954, ³ and since then it has been apparent that the majority of laboratory errors occur in the preanalytical phase, presumably because these steps involve more human tasks and are therefore more prone to errors. ⁴ As a profession, we have achieved exceptionally high standards in the analytical phase and are now striving to ensure that the quality outside of the laboratory is at the same level.

In his paper on the history of the preanalytical phase, ⁵ Walter Guder describes the first preanalytical issue that he had to address, the earliest described preanalytical ‘case’: samples from a certain location had higher rates of haemolysis than other locations. It transpired that the problem was due to contamination of samples with rain water, as they were carried across a yard to the laboratory. This is not a problem that would be encountered in the modern laboratory since the widespread adoption of closed blood collection in the early 1970s. ⁶ Numerous advances in equipment have helped improve the quality and stability of samples. These include urine collection devices in the middle ages, the introduction of basic blood tubes in the 1800s, centrifugation in the 1850s, anticoagulants in the 1930s, serum separators in the 1990s and finally, phlebotomy safety devices to avoid needlestick injuries in the 2000s. ⁶ However, the impacts of these earlier technological advances are unclear, as error rates have only been documented more recently. One innovation with proof of improvement is the implementation of electronic patient identification which has been shown to reduce wrong blood in tube errors up to five fold. ⁷

In the 1990s, Mario Plebani and the IFCC WG LEPS (International Federation for Clinical Chemistry Working Group for Laboratory Error and Patient Safety) began a project to document the types and frequencies of errors seen in a laboratory. ⁸ Once documented, they put in place processes to improve the error rates and reperformed the study 10 years later. ⁹ They demonstrated that by monitoring key performance indicators (KPIs) in the preanalytical phase, they significantly reduced error frequency from 0.47% to 0.309%. They further progressed this work and have been developing and evolving KPIs in the preanalytical phase, producing guidelines on what laboratories should be monitoring and providing tools that can be used to do so. ¹⁰

This idea of monitoring the preanalytical phase brings us to where we are now. As a profession, awareness and interest in the preanalytical phase is at its highest level ever. Through the requirement in ISO15189, the work of the IFCC WG LEPS and the EFLM WG-PRE (European Federation for Laboratory Medicine working group for the Preanalytical Phase), 94% of laboratories now collect data relating to quality in the preanalytical phase and are aware that the majority of laboratory errors occur in this phase. ¹¹ There have been a series of European biannual conferences organized by the EFLM WG PRE discussing the preanalytical phase, and from these, eight preanalytical aspects were identified, prioritized for standardization and the progress made was summarized in 2016. ¹² The successfully addressed issues covering some of these areas include:

Venous blood sampling for which a recent EFLM guideline on venous phlebotomy has been produced ¹³

Quality indicators for the preanalytical phase ¹⁰

Recommendations on standardized fasting requirements ¹⁴

Recommendations on patient identification ¹⁵

Recommendations on Order of Draw ¹⁶

The areas where work is ongoing include:

Test ordering appropriateness

Managing unsuitable specimens

Sample stability

Paediatric/neonatal blood sampling guidance

However, the production of guidelines and recommendations is not sufficient. The CLSI Guideline GP41 has clear guidance around patient identification, yet there is still a failure to do this correctly in 16.1% of cases. ¹⁷ Laboratorians now need to work together to promote the implementation of these guidelines and technologies to achieve the required level of performance.

There are a number of ongoing projects which address how we process and act upon the information we are collecting. If we are not going to act on the information we have, there is little point in collecting it. In order to address this, there have been separate surveys issued by the EFLM WG PRE and the ACB WG PRE to collect information on the current situation across the UK and Europe.^11,18,19 These showed that 94% of 1347 participants collected data on preanalytical errors. However, 31% of those collecting data did no further analysis, and of those that did, 33% took no further action regardless of the findings. Additionally, how and what data are collected and counted can vary. ¹⁸ The ACB WG PRE reviewed the various options for collecting data, recommending that when possible the laboratory information management system should be used as the recording tool. ²⁰ Even for the most commonly assessed preanalytical indicator, the Haemolysis, Icteric, Lipaemic (HIL) indices, there is significant variation in how the results of these indices are handled, ranging from simply documenting the findings through to rejecting the whole sample. From these studies, it is hoped that best practice guidelines will emerge so that the process can either be harmonized, or at the very least ensure the there is a robust evidence base to support the approach of an individual laboratory. ¹¹

The major challenge the laboratory has in addressing the issues in the preanalytical phase is to successfully target the staff involved in pre-analytical sample handling. These staff generally work outside the laboratory environment and often are not managed by the laboratory. It is essential that for these staff groups, there is appropriate and ongoing education on correct sample collection and handling procedures and on the implications of errors in the preanalytical phase. This may be via direct education sessions, eLearning or via direct feedback through sample reports or verbally.^12,21

Some tests require specific patient preparation, e.g. fasting or other lifestyle or medication adjustment for a period prior to testing. The execution and documentation of this are often poorly executed. The EFLM WG PRE has published guidance to standardize fasting time, but currently there are few guidelines or manuscripts summarizing how other factors can influence results and how they can be standardized to minimize their influence. ¹⁴ Such factors include medications, over the counter drugs, herbal remedies, physical activity levels, etc.

One of the biggest factors that might influence the quality of a sample is the journey of the sample to the laboratory. Currently, there is a raft of evidence on sample stability which is frequently conflicting or non-standardized. The conditions in which a sample is transported are often very variable, particularly with respect to time, temperature and light exposure. One of the key areas of focus over the immediate future will be to improve the quality of reporting of sample stability studies. This should mean that future studies will provide sufficient information to allow transfer of the findings to other appropriate healthcare settings. Standardization of reporting has the potential to allow collation of data into one large database. The technology to standardize, monitor and control the variables involved in transport procedures already exists but is not used routinely due to the costs involved.

Moving forward from the KPI work discussed above, if laboratory medicine is to truly move to a point where quality in the preanalytical phase is as well controlled as in the analytical phase, then participation in peer comparison schemes via EQA providers will be an important driver. This will enable laboratories that are outliers in terms of preanalytical EQA performance to critically assess the quality of their preanalytical phase or their monitoring of it. The interpretation of performance compared with peers is perhaps more complex than for other EQA schemes: laboratories flagged as having fewer preanalytical errors than its peers may indicate either excellent performance or alternatively incomplete detection and capture of preanalytical errors. The converse may be true for laboratories having higher preanalytical rates than peers. It is hoped that careful and considered use of preanalytical EQA performance data may drive up standards and help embed preanalytical quality in the culture of the laboratory. While it is evident that we are taking steps in the right direction, recent surveys illustrate that we are not yet where we need to be.^11,19

One final and important factor is the improvement of the appropriateness of test ordering. There are many ongoing projects in this field with the most promising ideas being around condition-specific requesting or via reflex-driven algorithms. This also covers reducing the use of repeated testing within inappropriate timeframes.

The future requires us to embed existing guidelines into routine practice and to audit their impact. This will produce the evidence base to support the development of further guidelines in areas where there is gap in our knowledge. To improve the service we provide to our patients, laboratories must not only monitor performance in the preanalytical phase but take corrective action where necessary to improve performance. This will require a collaborative approach with users of laboratory medicine to improve the quality of the patient experience.