The Value and Complexity of Infection Studies or Why we Bug the Data Managers.

Transcription

1 The Value and Complexity of Infection Studies or Why we Bug the Data Managers. Marcie Tomblyn, MD, MS, Scientific Director Manisha Kukreja, MBBS, MPH, Biostatistician Infection and Immune Reconstitution Working Committee Overview Indication for infection studies in transplant patients Definitions Study data needed Supplemental data requests 1

2 Why do we need to study infections? Significant cause of morbidity and mortality after transplant Patients may have chronic infections and receive transplant Newer drugs may change outcomes of infections after transplant Causes of Death after Transplants AUTO Relapse (75%) Organ toxicity (8%) IPn (2%) Infection (6%) GVHD (14%) HLA-ID SIB Other (9%) Other (13%) Relapse (38%) GVHD (14%) UNRELATED Relapse (32%) Infection (17%) IPn (5%) Organ toxicity (13%) Other (17%) IPn (7%) Organ toxicity 11%) Infection (19%) SUM05_20.ppt 2

3 Definitions Clinically significant infection Repeated infection Prophylaxis vs Treatment Clinically Significant Infection Identified infections that result in a change of therapy Suspected infections with supporting clinical or imaging findings (i.e. pulmonary infiltrate on chest CT) 3

4 So What s NOT an Infection? Culture-negative neutropenic fever without clear source Upper respiratory infections that are presumed viral but no virus identified Stool Candida Reporting Infections 4

5 Sites of Infection **Disseminated infections must have the organism identified at 3 or more non-contiguous sites 5

6 What is the same infection? (i.e. don t t report again) Bacteria 7 days All bacteria (except Clostridium Difficile) 30 days Clostridium Difficile 365 days Helicobacter pylori Virus 14 days VZV HZV Adenovirus Enterovirus Influenza virus Parainfluenza Rhinovirus 60 days CMV HSV Polyomavirus Fungal 14 days Yeasts Candida Cryptococcus 90 days Molds Aspergillus Fusarium Mucor Prophylaxis vs Treatment Prophylaxis: started about the time of conditioning to PREVENT infections Usually includes: Antibiotics Quinolones Bactrim (TMP/SMX) Antifungals Antivirals Treatment: drugs used for MANAGEMENT of the infection Example: d/c of Acyclovir and start Ganciclovir at time of CMV infection/reactivation 6

7 Infection Prophylaxis Where are the answers? What if you can t t find them? Dates of infection Microbiology records Dates of therapy Medication Administration Record (MAR) Still can t find it????? Estimate dates Please mark unknown 7

8 Specific Infection Data Viral loads (i.e. Hepatitis, HIV) Likely checked multiple times List all values available during the reporting period Be careful of the units of measurement! From the statisticians perspective 8

9 Supplemental Data Data that is not collected on the Comprehensive Report Form Often required in Infection Studies Treatment of infection Testing for diagnosis of infection Dates Prophylaxis Treatment Diagnostic test results Creation of Supplemental Forms Confirm that the data is not already collected on CIBMTR forms Create flow chart (hopefully similar to how the data is recorded in the medical chart!) Data requests are grouped Lab data Diagnostic tests Therapy 9

10 Creation of Supplemental Forms Medications include generic and trade names on forms Explanation of codes and definitions used on the forms can be found either: On the supplemental form directly In an accompanying manual In the Data Managers manual Why are we asking you a question you ve already answered??? To confirm data that may be confusing Ex. Hepatitis B surface antigen vs surface antibody To confirm that a patient actually should be included in the study in rare situations Ex. HIV positive **We will try and pre-populate the form with your previous response** 10

11 Example: Viral Hepatitis Data Manager Torture (I mean requirements!) Minimize use of Other, specify fields Unknown Contact the study CRC if There are potential recipients who fit study criteria but data were not requested You have ANY questions! 11

12 Reporting Dates Guidelines for estimation (since MDs are notorious for being inexact or illegible!) If month and year available but no day, use 15 If season available, report best guess of month and day You must tick the ESTIMATE box Reporting Duration of Therapy Date started Date stopped If therapy held for 7 days and then restarted, DO NOT list as stopped If on treatment until death, mark therapy stopped NO 12

13 Example: Duration of Therapy Reporting Doses Form will attempt to use a standard unit Convert dose into the unit requested (i.e. mg) Consult with pharmacist if needed Report the first dose as the starting dose Report maximum dose (if asked) What if the dose changes???? Use the starting dose 13

14 Example: Hepatitis Treatment What I do with the data you send Reasons for specific dates Calculate Time to infection Survival after infection and after transplant Study effect of prophylaxis or treatment on outcomes after infections Reasons for specific drugs Identify impact of certain medications on development or outcome of infections 14

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