Laboratory Investigations in Clinical Research

Transcription

1 Laboratory Investigations in Clinical Research Kari Pulkki, professor, UEF and ISLAB Introduction to Clinical Research, 22 nd of May 2017

2 Contents Clinical Laboratory today (ISLAB) How to perform a succesful study with laboratory tests? The value of laboratory tests Quality assurance of clinical laboratory Cooperation of investigator with ISLAB Collection of samples Research contracts Pricing and billing of Laboratory services Storage of samples To be stored (Talteen) samples Projects with external funding (etc. Drug companies) New biomarkers and methods Summary

3 Why blood sample Blood sample is the mirror of the body also DNA and RNA from the blood cells and tissues from stored samples You can analyse new markers, if the sample type and quality of the sample allows sample for Biobank

4 Laboratory Medicine laboratory tests of health care (blood, urine, feces, and other samples) With every test You should get additional information about the status or prognosis of the patient (evidence based medicine) % of physicians decisions are based partially or only on laboratory test results about 5 % of costs in health care are coming from Lab costs

5 Clinical laboratory process Interpretation patient history/ physical examination Lab request Test result Sampling Analysis

6

7 Accredited by FINAS acc EN and ISO 17025

8 The prerequisites for a succesful laboratory test result relevant clinical question (indication) often extra information regarding the patient are needed guidance for sampling correct sampling technique, preanalytical handling, transportation Good analytical quality QA, acceptance of the result fool-proof delivery of the test results Correct interpretation of the test result (for the individual patient) 8

9 The Quality of laboraty tests Accreditation, auditions, EQA (external quality assurance) Internal QA Correct level (EQA) Adequate reproducibility (IQA)

10 total error of the test result Preanalytical phase % Analytical phase 5-20 % Postanalytical phase %

11 centrifuged sample --> plasma/serum anticoagulant inside tube ---> plasma (clotting factors inhibited)) No anticoagulant (glass tube) --> serum (it does not include clotting factors)

12 How do You interprete the test result? Reference limit (ref value) decision limit (like with cholesterol) critical value (like P-K (Potassium) 6.5 mmol/l)

13 Calculation of reference values for a laboratory test reference population reference sample recruitment of reference persons sampling according to the current protocolls laboratory analysis Statistical analysis

14

15 Factors influencing individual laboratory results age sex nutrition pregnant? menstrual cycle time of the day time of the year weight /BMI posture

16 Test Value healthy Ideal state sick No false positives or negatives

17 Cut-off values healthy sick test result Adjusted Limit no false positive +2SD False postives

18 Biomarker publications in Medline metabolomics, proteomics, genomics, translational biology No biomarker has yet come to clinical practice although NIH has granted 2,5 Billion USD since 2000 into biomarker-research

19 19

20 The Pipe-line of biomarkers Biomarker discovery and qualification Assay optimization and performance requirments for biomarker evaluation and validation Biomarker implementation Biomarker introduction into clinical practice 20

21 Biomarker is a measure of disease processor, biological process, is related to disease activity, survival or response to treatment -

22

23

24 Examples for failure and success PAPP-A (pregnancy-associated plasma protein A) heparin-related sample problems, with-drawn MPO (myeloperoxidase) sample problems, wd scd-40l, sample problems, wd Copeptin (C-terminal part of arginin-vasopressin) in association with Tn H-FABP (heart-type fatty-acid binding protein) Acute kidney injury (AKI) markers pre-eclampsia (new markers are coming) breast cancer (her/neu) acute kidney injury markers (NGAL, IL-18?) stroke markers

25 Quality of the sample hemolysis lipemia (eg. staying at +4 C) bilirubin (icterus) creatinine and other markers of renal insufficiency various autoantibodies (anti-igg, anti-mouse Ab) hyperproteinemia = very high proteinn concentration = high viscosity

26 Esityksen nimi / Tekijä

27 Scope and view of specialist in emergency medicine and cardiology are different! Efficient rule-out Specific rule-in Diagnostic criteria for specific diagnosis and treatment fullfilled

28 The cooperation of the Investigator with ISLAB try to search the literature for what analyses do You need for the project (sample, and methods) ISLAB ohjekirja /manual contact through e mail/by phone research technician/co-ordinator of the lab a brief description of the project, schedule, laboratory tests, sample volume, sampling ISLAB will respond how/if it may be performed, Investigator will fill in the forms, ISLAB will fill in the rest, a copy is sent back to the Investigator If needed, there are several cycles of consultation, regarding, choice of analytes, sampling, choice of methods, storage, and interpretation with ISLAB experts 28

29 The prerequisites for new interesting biomarker research! Is the test already in the menu of ISLAB (about 2000 tests) Is the test in the menu of other laboratories (samples will be sent) Are there kits/methods available which could be used, validated and analysed (reference values?) Schedule of sampling Additional work needed for setting up the analysis, validation, calculation of reference values (additional costs?) 29

30 Collection of samples Who takes the samples (schedule, off-hours? 24/7?) sample: whole blood, serum, plasma (what kind of plasma?) urine, feces, transudate, exudate, CSF, bone marrow, tissue Do we need temperature-regulated centrifuge (cold?) special tubes? into how many tubes should the sample be divided into after centrifugation? Freezing into 20 C, 70 C? How many freeze/thaw cycles? How and were the samples are stored? Biobanks? For how long can we store? Costs for the sampling and storage 30

31 Contract on sampling and analyses in ISLAB KYS intra > scientific research > Islab For all research projects Principal investigator /Pharma company outside KYS KYS investigators (eg. VTR): a direct discussion/contract what to do and at what price Other (eg. university investigators): a direct discussion/contract what to do and at what price 31

32 External investigator (Pharma company etc.) Contract with KYS also includes laboratory tests from ISLAB includes also now the contract with ISLAB background of the project parties what is agreed on ALV or not Y tunnus ethical committee/other acceptance All the contracts will be into registry of projects of KYS 32

33 To be stored (Talteen) näytteet You want to collect all samples at the same time (also to be analysed in the future) new biomarkers, that we do not yet know of In a multicenter or co-operation study samples will be collected for a long time, and then sent all together In the contract ISLAB will give a code for the lab tests/request into Multilab. It also includes the sampling, and handling instructions ISLAB will store the samples for a year and then we need to know, what to do All sample types may be stored Prices; sampling 8,0 + handling and storage 1,8 6 depending on the protocolls and freezing temperature Pt Tutk.näytteet samples to be stored

34 Storage of samples because of limited space, the samples cannot be stored for ever Most of the clinical samples are destroyed the next morning Some samples are stored for eg. 2 weeks research samples are destroyed or handed over to investigators when the results have been obtained (it is all in the contract) To be stored-samples (Talteen näytteitä ) will be stored for a max one year with a special agreement ISLAB may store the samples for a longer time (annual fee etc.) 34

35 Pricing of Project samples The basic principle: the same price as listed for health care A special price for sampling (for visits, not for the amount of tubes, nor the amount of analyses) Eg. sampling with B PVK = 8,0 + 2,80 Eg. sampling with P Alat, P Amyl, P Afos, S CDT = 8,0 + 1,9 + 1,8 + 1, No animal / veterinary samples are analysed 35

36 Billing of research projects Through Multilab in KYS intra: How to make the request for research project samples and to give the information on payer/billing address Some tests are billed with conventional billing The research technician of ISLAB opens the possibility to make the requests and billing and closes it. She also follows the billing and number of samples taken. She sends the final bill 36

37 Contracts with Pharma projects includes contract of the sampling and analyses Permissions protocolls from CRA/PI/Investigator/research nurses Accreditation documents, certificate, CV:s of responsible lab officials and professionals Method information, reference values Exact information and follow-up of freezers. like temperature follow-up Strict documentation of the process, like problems in sampling, handling and follow-up. Pt Koord. cost 100 or multiple of 100 based on amount of work 37

38 38

39 39

40 Additional information obtained with laboratory tests patient characteristics are connected with genetic or biochemical information information instead of numbers The interpretation will be more accurate/individual (like PSA) new biomakers will improve the targeting of new (expensive) drugs/therapies

41 You can at any phase contact ISLAB 41