Interview with Maria Shipkova, IATDMCT Director of Education and Communications Committee Vice-Chair

Can you tell us a little bit about your respective roles? What is a typical day like for you?

I am the head of the section for therapeutic drug monitoring and clinical toxicology in a central clinical laboratory institute at the Klinikum Stuttgart that provides diagnostic services for four tertiary care hospitals, as well as a number of outpatient centers. My first responsibility is to keep all processes in our section working well and continuously adapt the spectrum of analyses to meet current needs.

My second responsibility is to manage the clinical studies which we are involved in, as well as for the services we provide as a reference laboratory for the diagnostic industry. In this respect I supervise students during practical semesters, for bachelor and master theses, that are mostly linked to our ongoing research projects.

Due to the wide range of my duties, every day is different. A rough description would be that in the morning the first thing I do is to visit the lab to check all assays that were run overnight, and advise my technicians if there are any analytical or technical problems. After these morning activities I usually spend time consulting and in meetings with colleagues and customers, as well as in discussions with my students and other members of our research team. In the afternoon I perform the evaluation and medical validation of lab results and this is when I get to work on new assays and assay modifications. In the evenings, I frequently draft manuscripts and perform voluntary work, such as my services for the Communication Committee of IATDMCT or my engagement as Director of Education.

Is there anything that your laboratory does or that is done at your centre that you would consider innovative?

In our laboratory, we are really happy to be continuously part of different innovative projects. For example, we are building a bio-bank with samples from kidney transplant recipients which allows us to perform studies on new biomarkers to improve patient care in transplantation. A very exciting example is a project funded by the German Federal Ministry of Education and Research (BMBF) in which we investigate together with our transplant center as well as scientific and industry partners the potential of graft derived cell free DNA as a biomarker for kidney damage.

Another innovative project we are currently fostering is the extension of our TDM services for antibiotic drugs to better guide the therapy of intensive care unit patients suffering from severe infections. The special feature of this project is the close collaboration between the TDM laboratory, the section for medical microbiology in our institute, the hospital pharmacy, and the intensive care units. We provide plasma concentrations in the morning, in a timely manner, and colleagues involved in continuous ward pharmacy services use these for dose adjustment in coordination with the infectious diseases specialists and clinical microbiologists. Although this service is common practice in other medical centers, I think that the most innovative aspect is the excellent cooperation between different professions which renders this service highly effective and fast.

What technological innovations have entered into use during your career that have permitted a change, or evolution, in practice?

The most important technological innovation that has entered into use in laboratory medicine during my career is mass spectrometry. It has revolutionized TDM services by making it possible to measure a very broad spectrum of drugs that was not possible before with conventional methods such as immunoassays or HPLC without MS-detection. I am fascinated by the opportunity to rapidly respond with new assays and with high analytical reliability. Likewise fascinating is the shortening of analytical response times in the field of clinical toxicology and drugs of abuse testing by the introduction of LC-MS-based procedures versus GC/MS. For instance, we are just introducing the ion trap MS-based methodology with the ToxTyper instrument for drugs of abuse and clinical toxicology screening in our section. Through its software, which is specifically designed for emergency use and by less experienced staff, we expect a leap in our services, particularly when expert technicians are not available. Of course I am aware of the challenges we face regarding the mass spectrometric analytics, but I am also confident that this detection technique will be further developed to become a reliable standard technique comparable to the situation we are experiencing with other techniques in a routine clinical laboratory. Automation, multiplexing, and miniaturization are currently the focus of intensive research.

Another important technological innovation is the emergence and accessibility of web resources and software that support our work in many fields such as prediction of drug-drug-interactions, dose adjustments, or in the investigations of poisoning. This helps to enhance the value of CT and TDM services for routine clinical use.

Of course, molecular techniques such as NGS and chip arrays have made significant progress and lead to the concept of personalized medicine particularly in oncology. Unfortunately, the impact on CT and TDM in general is so far comparably little although the information generated by these techniques is highly relevant. I am optimistic that in the future concepts will be developed on how this information can be better incorporated in treatment decisions.

How did you become interested in your area of expertise?

As a physician my deepest conviction is that you can become interested in every field of medicine if you get the opportunity to learn it in detail and from good teachers. This was the case with me and the field of TDM/CT. When starting my career in the Department of Clinical Laboratory in Sofia, Bulgaria, I was marginally aware of what TDM was. I was lucky to meet and work with two excellent teachers – Professor Dobrin Svinarov in Sofia and Professor Michael Oellerich in Goettingen, Germany. They are definitively responsible for a considerable part of my enthusiasm regarding TDM/CT. Both are not only well recognized experts in TDM worldwide, but are also longstanding members of IATDMCT. Therefore, it was not a surprise that I started attending IATDMCT congresses very early in my career and I have had the great honor to become acquainted with many wonderful colleagues with diverse expertise and innovative ideas. These exciting contacts have further triggered my professional path. I am extremely grateful for all these encounters.

Is there anything that you’ve seen elsewhere or heard about and thought “I’d like to incorporate that idea at my center”?

This is something that happens continuously to me. Every time I have to cope with a new challenge in daily work, I use the opportunity to take a look at how other colleagues deal with similar situations and what is their experience. The exchange at meetings is a wonderful source for new ideas. The chance to do this within our IATDMCT community is a benefit I highly value. Just to give an example, a recent task that I realized is the online connection of all our instruments to the laboratory information system and the automation of our pre-analytics, a project that is just underway.

What sort of research do you have on the horizon that you think might influence clinical practice in the future?

I suppose that you have my personal and subjective horizon in mind. The research that I have on my personal horizon is of analytical nature. As I already mentioned the focus of our current research is on new biomarkers that may help to improve patient care in clinical organ transplantation. This topic is a very hot one and many groups are working in this field. Our particular focus is not just on a biomarker but on the combination of biomarkers and the method(s) available for their analysis. My personal appraisal of the current situation is that clinical investigations of many interesting new biomarkers are performed with assays that are not really analytically mature for diagnostic purposes. Moreover, integral parts of the analytical procedure e.g. the pre-analytics is often not well evaluated. Under these conditions, benefits may fade simply due to low analytical performance. Therefore, efforts should be made to ensure the quality of analytical results as well as the turn-around-time they can be reported to the clinicians is appropriate for the clinical needs. Appropriate analytical validation, harmonization, and if possible, standardization are some key words in this context. Fortunately, a trend to pay more attention to this aspect is on the horizon. This is one of the tasks which the Biomarker Working Group of the Immunosuppressive Drugs Scientific Committee of IATDMCT, of which I am a member, has set itself.

In a more general perspective, I am enthusiastic that the research in the fields of proteomics and metabolomics but also the knowledge being continuously generated by the use of the NGS-technique has the potential to considerably influence clinical practice in the future.

What do you consider is the future for TDM and CT? What are you excited about? What are the challenges we face?

My vision is more readily, broadly and timely available services in the fields of TDM and CT. I think that if this can be achieved, the general recognition of these fields and more importantly their rigorous implementation into the clinic to improve patient care will rise in significance. This can be achieved by optimization, simplification, and standardization of all essential components building the analytical/diagnostic process in full. Alongside assay automation and commercialization key words in this connection are electronic patient records, patient near diagnostic solutions, web/software based resources to support result interpretation and therapeutic decisions, new sampling strategies, use of alternative matrices, etc.

Importantly, advancing in this way the challenge is not to lose sight of the needs of the individual patient. The improved access to services and information will not replace an experienced specialist for consultation. More readily available TDM / CT tools only make sense in the context of a well-developed network of qualified scientists and medical doctors who actively collaborate. And thus we return to my example of a multidisciplinary cooperation for TDM for antibiotics, mentioned above.

Finally, more sophisticated instruments and cutting edge technology will further require lab specialists with a high level of specific training to be introduced to TDM and CT services and therefore the field of new analytical developments will still remain a domain of highly specialized laboratory units.