Roundtables

Roundtable R2301: Statistical Models Included In Software For Immunosuppressive Drugs And Antibiotics Bayesian-Based Therapeutic Drug Monitoring: Experiences Sharing And Standards Definition

Leader: Flora Musuamba Tshinanu, Louvain Centre for Toxicology and Applied Pharmacology, Université Catholique de Louvain, Belgium

Objectives:

At the end of the session, the participants will be able to:

Have an overview of the softwares available for TDM of immunosuppressive drugs.
Objectively assess the variability in the dosage regimen recommended by various software/centers.
Provide consensual guidelines recommending the use of particular mathematical models, statistical approaches, and covariates to be integrated in the software.

Description:

Safe and effective immunosuppressive therapy constitutes an important determinant of the outcome of solid organ transplantation. Even though dose individualization is agreed to be necessary, approaches used for therapeutic drug monitoring are very variable across clinical centers worldwide. The roundtable will focus on conducting a deep discussion around the consistencies and discrepancies between different models included in currently available software for immunosuppressive drugs TDM.

Roundtable R2303: Biologics And Beyond: A New Frontier In TDM?

Leader: Michael Milone, Assistant Professor, Pathology and Lab Med and Associate Director, Toxicology Lab, University of Pennsylvania Health System, USA

Objectives:

This roundtable presentation aims to provide a high-level overview of biologic therapies currently approved or in clinical trials for cancer with a focus on complexities of these therapies compared with traditional small molecule drugs. A review of some of the challenges associated with biologic therapies and the opportunities for monitoring of biologic therapy for both efficacy and toxicity will be discussed. At the end of the session, the participants will be able to:

Understand the breadth of biologic agents currently in use or development for cancer treatment.
Describe some of the challenges associated with biologics.
Describe potential opportunities for the laboratory monitoring of some biologic therapies.

Description:

Biologic therapies (so called biologics) represent a rapidly growing area of new therapeutic options for patients with cancer. These new therapeutics come in a variety of forms from small peptide and proteins to complex cellular therapeutics. This roundtable presentation aims to provide a high-level overview of biologic therapies currently approved or in clinical trials for cancer with a focus on complexities of these therapies compared with traditional small molecule drugs. A review of some of the challenges associated with biologic therapies and the opportunities for monitoring of biologic therapy for both efficacy and toxicity will be discussed.

Roundtable R2304: Urine Drug Testing And Its Role In Pain Management

Leader: Kamisha Johnson-Davis, Assistant Professor, University of Utah, ARUP Laboratories, USA

Objectives:

Address the importance of urine drug testing to monitor patient adherence/compliance for pain management.
Review the pros/cons of drug testing via point-of-care, immunoassay, mass spectrometry.
Discuss the basics of result interpretation.

Description:

This session will discuss the role of urine drug testing to monitor patient adherence for pain management. Urine drug testing is often utilized assess risk for opioid therapy. This session will review the pros/cons of drug testing via point-of-care testing, immunoassay, and mass spectrometry, specimen validity testing to detect adulteration/substitution, and result interpretation.

Roundtable R2305: Monitoring Biological Therapies (Interferon-Therapies Or Anti-Tumor Necrosis Factor Therapies)

Leader: Manuela Neuman, In Vitro Drug Safety & Biotechnology, University of Toronto, Canada

Objectives:

Understand the role of biological therapies directed towards diseases in dermatology, gastroenterology and hepatology
Understand how the use of the therapies impact the immune system.
Monitoring biological therapies in clinical laboratory.

Description:

This round table is an integrative presentation that bridges preclinical and clinical research looking at different aspects of monitoring biological therapies in clinical laboratory. Moreover the round table will focus on molecular mechanisms of biological therapies directed towards diseases and how the use of the therapies impact the immune system. We strongly encourage the participants with different interests in therapeutic drug monitoring an clinical toxicology to interact. We intend to provide the opportunity for society members that have main concern monitoring biomarkers in clinical trials to learn new research avenues.
The round table will provide an unique and therefore, very exciting opportunity for clinical chemists and toxicologist as well as physicians and industry representatives working in the area of molecular pathology, immunology, pharmacology, dermatology, gastroenterology and hepatology to be updated and to discuss their clinical and basic research ideas with international experts. This round table will be an ideal platform for promoting interactions between translational and clinical laboratory in all aspects of biological therapies. Young members and students are welcome to come, and discuss their experiences in this field.

Roundtable R2306: Use Of Proficiency Testing To Improve Analytical Results

Leader: Daan Touw, Clinical Pharmacological and Toxicological Lab., Aptheek Haagse Ziekenhuizen, Netherlands

Objectives:

At the end of the session, the participants will be able to:

Understand what proficiency testing is.
Understand the importance of proficiency testing for laboratory accreditation.
Understand what commutable samples are.

Description:

Proficiency testing is mandatory for Laboratories to be accredited in their field. Proficiency samples are distributed to test the analytical accuracy and are sometimes accompanied with a case together with questions. Besides the analytical accuracy, the answers to the questions are judged.
For a correct judgement of analytical accuracy, samples do have to behave like real patient samples. This means that samples need to be commutable. For samples containing drugs, usually blank serum or plasma is used that is spiked with the drug and samples are sometimes freeze-dried for stability.

In the session it will be demonstrated how analytical improvement can be achieved by participating in proficiency testing.

WEDNESDAY, SEPTEMBER 25

Roundtable R2501: Anti-Retroviral Assessment In Blood For Support Of HIV-Prevention Clinical Trials

Leader: Mark Marzinke, Johns Hopkins Medical Institutions, USA

Objectives:

At the end of the session, the participants will be able to:

Have an understanding of the small molecules developed and implemented as antiretroviral therapies (ARTs).
Describe the utility of qualitative and quantitative monitoring of antiretroviral agents in clinical trials.
Describe opportunities for antiretroviral drug testing in the laboratory for monitoring therapeutic regimen compliance and adherence.

Description:

Antiretroviral drugs are approved for HIV treatment in both single- and multi-drug formulations; further, antiretroviral therapies have been successful for HIV prevention in a variety of clinical settings. Quantitative monitoring of antiretroviral drug levels can be used in the assessment of pharmacokinetic-pharmacodynamic relationships, as well as in the determination of safety and efficacy parameters. Qualitative screening for antiretroviral drugs may be used to assess compliance and adherence, as well as detect off-study use. This roundtable will include a review of the use of qualitative and quantitative liquid chromatographic-mass spectrometric methods for screening and targeted analyses, respectively.

Roundtable R2502: An Introduction To Peptide Quantification By HPLC-MS/MS

Leader: Paul Taylor, Dept. of Clinical Pharmacology, Princess Alexandra Hospital, Australia

Objectives:

At the end of the session, the participants will be able to:

Understand the general approach to develop an HPLC-MS/MS method for peptide quantification.
Identify the specific challenges to measuring peptides.
Troubleshoot and understand the potential pitfalls of measuring peptides by HPLC-MS/MS.

Description:

The use of peptides as therapeutic agents and biomarkers is increasing. Thus the measurement of peptides may become a progressively more important part of the clinical laboratory’s analytical requirements. Typically, peptides have been measured by immunoassays. These methods can suffer from lack of selectivity or availability of suitable antibodies. The opportunity to use HPLC-MS/MS for such measurements has tremendous potential. This Roundtable will provide an overview on establishing an HPLC-MS/MS method for peptide quantification. There will be particular focus on the specific challenges and pitfalls of measuring peptides (e.g. analyte stability, adsorption, internal standard selection, etc.).

Roundtable R2503: How To Utilize The UGT1A1 Genotype Testing For Individualized Irinotecan Dosage

Leader: Yuichi Ando, Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Japan

Objectives:

At the end of the session, the participants will be able to:

Explain the reason patients who are homozygous for UGT1A1*28 have an increased risk of irinotecan-induced toxicity.
Correctly identify and describe which patients should be tested for UGT1A1 polymorphism.
Develop a plan to integrate UGT1A1 testing into clinical practice of irinotecan chemotherapy.

Description:

Irinotecan often causes severe neutropenia and diarrhea in cancer patients who have decreased drug metabolism of UGT1A1. By determining the UGT1A1 genetic polymorphism, we can identify which patients are likely to experience severe toxicity and which are not. This session will discuss how we can integrate this pharmacogenetic biomarker into clinical practice of irinotecan chemotherapy.

Roundtable R2504: Setting Up A Pain Management Testing Reference Laboratory: Experience In Our Journey

Leader: Ping Wang, Pathology and Genomic Medicine, The Methodist Hospital, USA

Objectives:

At the end of the session, the participants will be able to:

Describe the overall process of setting up a pain management testing reference lab.
Describe the typical test menu of a pain management testing lab.
Describe several potential pitfalls in the process.

Description:

In this roundtable presentation, I will discuss the experience gained during our process of setting up a pain management testing reference laboratory. This is currently a process in progress. Our discussion may include the following aspects: motivation, a simple market analysis, client visit, assay development and clinical testing.

Roundtable R2505: Azole Antifungal TDM

Leader: Deborah Marriott, Microbiology and Infectious Diseases, St. Vincent’s Hospital, Australia

Objectives:

At the end of the session, the participants will be able to:

To understand the pharmacokinetic and pharmacokinetic parameters of the azole anti-fungal agents.
To recognize the importance of TDM in a variety of clinical settings to optimize safety and efficacy.

Description:

The azole anti-fungal agents fluconazole, itraconazole, voriconazole and posaconazole, have transformed the prophylaxis and treatment of invasive fungal infections. Fluconazole has been perceived to be a very safe agent and TDM has not been widely performed. However data from our unit suggests that under-dosing is common, particularly in patients undergoing renal replacement therapy, and that TDM is essential to optimise patient outcome. Itraconazole, voriconazole and posaconazole have wide inter- and intra-patient variation and significant drug-drug interactions. In addition recommended serum levels for efficacy and toxicity are now well described, suggesting an important role for TDM.

Roundtable R2506: Models Of Decision Support

Leader: Franck Saint-Marcoux, Pharmacist – Researcher, Department of Pharmacology and Toxicology, University Hospital of Limoges, France

Objectives:

At the end of the session, the participants will be able to:

Understand how to combine multiple modeling approaches (parametric and non parametric) to increase confidence in dose proposals performed in a routine clinical setting.
Understand value of TDM in aminoglycosides in current clinical practice.
Understand how to implement PK tools in an expert system accessible through a secured website.

Description:

When pragmatically used, Pharmacokinetic (PK) and Pharmacokinetic-Pharmacodynamic (PK-PD) models can be efficient, powerful and informative tools in clinical settings, when adverse events or hazardous efficacy render individual dose adjustments necessary. During the roundtable, the participants will find practical information about different population PK approaches, Bayesian data analysis and examples of effective applications on an expert system accessible through a secured website.

Together with the speaker, the participants will be invited to use the system themselves to perform dose adjustments of antibiotics (aminoglycosides and glycopeptides), anticancer drugs (methotrexate) and immunosuppressive drugs (cyclosporine, tacrolimus…). The participants are therefore kindly requested to bring their own laptops in order to directly access the website.

Roundtable R2507: What’s New In Aminoglycoside TDM?

Leader: Erik Van Maarseveen, Lead Pharmacist of the TDM & Toxicology Laboratory, University Medical Center Utrecht, Netherlands

Objectives:

At the end of the session, the participants will be able to:

Understand the mechanism of aminoglycoside toxicity.
Understand value of TDM in aminoglycosides in current clinical practice.
Understand the proposed strategies of optimizing the efficacy/toxicity balance of aminoglycocides in various populations.

Description:

This session will primarily cover recently explored Dosing & TDM strategies to optimize the efficacy/toxicity balance of aminoglycosides. Prior to addressing the clinical potential of newly developed strategies, a brief introduction of the mechanism of aminoglycoside toxicity and current clinical practices will be discussed. Unpublished data from a number of recently performed studies will be presented.

THURSDAY, SEPTEMBER 26

Roundtable R2601: 2D And 3D Predictions Of Immunoassay Cross-Reactivity

Leader: Matthew Krasowski, University of Iowa, USA

Objectives:

At the end of the session, the participants will be able to:

Define how immunoassay cross-reactivity may cause false positive and false negative test results in drug of abuse screening assays.
Describe how immunoassay cross-reactivity is related to molecular similarity of compounds to the target molecules of the assay.
Identify how two-dimensional and three-dimensional similarity analysis may be able to predict and prioritize compounds for cross-reactivity testing, including for emerging drugs such as the “designer” amphetamine-like (e.g., “bath salts”) and cannabinoid drugs.

Description:

Immunoassays are widely used for detection of drugs or drug metabolites. A common clinical application is drug of abuse/toxicology screening performed on urine or other body fluids. One limitation of immunoassays is interference caused by compounds with structural similarity to the target molecule(s) of the assay (i.e., typically the hapten or haptens against which the assay antibodies were generated). Such cross-reactive molecules can be structurally related drugs, drug metabolites, or endogenous compounds. This session will describe the use of computational methods to predict cross-reactivity of compounds with drug of abuse immunoassays. Two-dimensional (2D) and three-dimensional (3D) computational modeling methods have been used to predict the cross-reactivity of a wide variety of drug of abuse and therapeutic drug monitoring immunoassays. 2D similarity methods are computationally fast and can be used to screen large numbers of compounds. The application of these methods to immunoassays for designer amphetamines (e.g., “bath salts”) and synthetic cannabinoids will be described.

Roundtable R2602: Using Liquid Chromatography Time-Of-Flight Mass Spectrometry (LC-TOF-MS) For Compliance Monitoring In Pain Management

Leader: Stephanie Marin, R&D Investigator, ARUP Laboratories, USA

Objectives:

At the end of the session, the participants will be able to:

Realize the advantages of LC-TOF-MS for detection of drugs in pain management compliance monitoring.
Appreciate the difference between using LC-TOF-MS for detection of drugs vs immunoassay with reflex to confirmation.
Understand the difference between LC-TOF-MS and other mass spectrometric techniques.

Description:

Most pain management patients must submit to compliance monitoring to ensure proper use of drugs prescribed and demonstrate absence of non-prescribed medications. Short time-to-result is important to maintain therapy. This testing is usually done with point-of-care (POC) devices or some type of drug screen, followed by confirmation by GC-MS or LC-MS/MS. LC-TOF-MS can provide more sensitive and specific detection than these screening methods, and since specific drugs and metabolites are identified, subsequent confirmation and quantitation may not be necessary. Applications of LC-TOF-MS for pain management testing using urine and plasma will be presented and discussed.

Roundtable R2603: Drug Transporters: Update 2013

Leader: Tomohiro Terada, Department of Pharmacy, Shiga University of Medical Science Hospital, Japan

Objectives:

At the end of the session, the participants will be able to:

Know the recent topics of drug transporters.
Discuss the clinical implication of drug transporters.
Share the information about clinical application of drug transporters.

Description:

Drug transporters have been recognized as a key determinant for drug absorption, distribution and excretion. To date, a variety of human drug transporters have been cloned, and a large number of biochemical, genetic and clinical evidences have been accumulated. This session will discuss the possibilities about clinical application of drug transporters to individual pharmacotherapy.

Roundtable R2604: Alcohol And Drug Use; A Deadly Combination

Leader: Manuela Neuman, In Vitro Drug Safety & Biotechnology, University of Toronto, Canada

Objectives:

At the end of the session, the participants will be able to:

Understand the different aspects of alcohol-induced organ damage.
Understand the specific measurements of alcohol-induced liver disease.
Understand therapies and alcohol use are deadly.

Description:

This round table is will focus on molecular mechanisms of biological therapies in the presence of alcohol consumption. We encourage the participants with interests in drug of abuse monitoring an clinical toxicology to connect with our continue interest in this area.
The round table will provide a stimulating prospect for clinical and laboratory toxicologist working in the area of pharmacology to be updated and to discuss their experiences. This round table will be a platform for promoting interactions between clinical and laboratory aspects of drug-interactions.

Roundtable R2605:Monitoring Of Biomarkers In Alzheimer Disease

Leader: Magda Korecka, Dept. of Pathology & Laboratory Medicine, University of Pennsylvania, USA

Objectives:

At the end of the session, the participants will be able to:

Understand sample preparation on mixed mode cation exchange µelution SPE columns
Get important information about the challenges involved in establishing a validated method for Aß peptides .
understand the need for an extended method validation protocol.

Description:

Alzheimer’s disease (AD) is the most common form of dementia, a neurologic disease characterized by loss of mental ability that interfere with normal activities of daily living. Other the past two decades, clinical studies have provided evidence that cerebrospinal fluid (CSF) amyloid beta (Aß) 1-42, total tau and tau phosphorylated at Thr181 are reliable biochemical markers of AD neuropathology. The single-plex ELISA kit and multiplex kit for xMAP are the most widely used immunoassay platforms for measurement of CSF AD biomarkers. However, the wide variability of AD CSF biomarker concentrations depending on the study is one of the main limitations for use of these biomarkers for research purposes at the present time. There is a critical need for a standard reference material and reference method/s. It has been proposed that liquid chromatography with mass spectrometric detection can be used as a reference method to determine the absolute Aß concentration in CSF. During this Roundtable our newly developed and extensively validated 2D-LC-MS-MS method for determination of three different species of Aßpeptide in CSF will be discussed.

Roundtable R2606: TDM Of The ICU Patient – A Review Of The Literature

Leader: Daan Touw, Clinical Pharmacological and Toxicological Lab., Aptheek Haagse Ziekenhuizen, Netherlands

Objectives:

At the end of the session, the participants will be able to:

Understand the typical pharmacokinetic differences in ICU patients.
Understand the effect of continuous dialysis on pharmacokinetics of drugs.
Understand the effect of low serum albumin on pharmacokinetics of drugs.

Description:

ICU patients are pharmacokinetically a challenge for therapeutic drug monitoring. ICU patients are treated with various vasopressive drugs that have effects on renal and/or hepatic blood flow which will have effect on renal and/or hepatic clearance.

ICU patients often have severe renal dysfunction, for which continuous renal replacement therapy is given. The effect of continuous renal replacement therapy on drug behavior is discussed.
Another condition that may have effect on drug behavior is hypoalbuminemia. The effect of hypoalbuminemia on pharmacokinetics will be discussed.

Roundtable R2607: Ion Suppression And Validation Of HPLC-MS/MS Assays – A Review Of The Literature

Leader: Ross Norris, Australian centre for Paediatric Pharmacokinetics, Mater Pharmacy Services, Australia

Objectives:

At the end of the session, the participants will be able to:

Understand ion suppression.
Understand ways to remove/minimize the impact of ion suppression on assay validity.
Learn the current approaches to assessing ion suppression impact.

Description:

This session will look at the history of ion suppression in HPLC-MS/MS and its importance, followed by literature reports indicating ways to minimize ion suppression and also ways to assess the presence and/or impact of ion suppression during assay validation.