EPI 218 Database Management for Clinical Research Michael A. Kohn, MD, MPP January 10, 2010

Clinical Research* Choose the study design, and define the study population, predictor variables, and outcome variables; measure these variables and anticipate problems with measurement; analyze the results In this course, we discuss the “nitty gritty” of collecting, storing, updating, and monitoring the study measurements. *Private companies that make data management systems for clinical research understand “clinical research” to include only RCTs preparatory to FDA drug or device approval, not observational studies.

Assumptions about Students Actively involved in a clinical research study Some experience with entering and maintaining data in single-table spreadsheet or statistical software

Outline Housekeeping Data Tables –Rows = Records; Columns = Fields Normalization of Data Tables Queries Front End or Interface/On Screen Forms

Housekeeping Epi 218

Course website: Labs will be in China Basin Landing 6704 with overflow into 6702, 8:45 – 10:15 (For log-on: Citrix Metaframe Presentation Server  MS Office Desktop “Learn MS Access 2000” video Username: ucsfdbclass Password: access2000 (We can also loan you the video on CD.)

Lab Instructors Maurice Garcia Others to be named later.

Course Objectives Learn how to develop a multi-table, relational database for a research study. We will be using Microsoft Access*, but we are familiar with other database software. Learn how to query a database for monitoring and analyzing data in a research study. Example: Infant Jaundice Study *SQL-based, widely available, desktop DBMS

Requirements Turn in all 4 assignments on time Fill out course evaluation.

Assignment 4/Final Project Due 2/16/2010 Send in a copy of your research study database* with a data management plan. We prefer a database that you are currently using or will use for a research study. However, a demonstration or pilot database is acceptable. *If you are unable to package your database in a file to , you can send us a link or work out another way to review your database.

Assignment 4/Final Project Due 2/16/2010 If you are doing secondary analysis of data collected by someone else, obtain the data collection forms* used in the original data collection, set up a new database that you would use for a follow-up study. *Often easily obtained by doing a Google search or ing the author of the original study.

Assignment 4/Final Project Due 2/16/2010 Start thinking about this now. Build up your own study database as you work through the labs. Use extra time in lab to work on your study database. Set up appointments with course faculty early.

TICR Professional Conduct Statement Clarifications for this class I will maintain the highest standards of academic honesty I will neither give nor receive aid in examinations or assignments unless such cooperation is expressly permitted by the instructor I will conduct research in an unbiased manner, reports results truthfully, and credit ideas developed and work done by others I will not use answer keys from prior years I will write answers in my own words, and, when collaboration is permitted, acknowledge collaborators when answers are jointly formulated For Epi 218 – Just don’t turn in somebody else’s work as your own.

Rows = Records = Entities Columns = Fields = Attributes Data Tables

DCR Chapter 16 Exercise 2 The PHTSE (Pre-Hospital Treatment of Status Epilepticus) Study was a randomized blinded trial of lorazepam, diazepam, or placebo in the treatment of pre-hospital status epilepticus. The primary endpoint was termination of convulsions by hospital arrival. To enroll patients, paramedics contacted base hospital physicians by radio. The following are base-hospital physician data collection forms for 2 enrolled patients: Lowenstein DH, Alldredge BK, Allen F, Neuhaus J, Corry M, Gottwald M, et al. The prehospital treatment of status epilepticus (PHTSE) study: design and methodology. Control Clin Trials 2001;22(3): Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 2001;345(9):631-7.

Display the data from these 2 data collection forms in a 2-row data table. Subjec tID KitNum ber AdminDat e Admin Time SzStopPre Hosp SzStopPreHos pTime HospArrT ime HospArrS zAct HospArrG CSV 189A3223/12/199417:39FALSE 17:48TRUE 410B53612/1/199801:35TRUE01:3901:53FALSE4

Create a 9-field data dictionary for the data table Field Name Data TypeDescriptionValidation Rule SubjectIDIntegerUnique Subject Identifier KitNumberText(5)5-character Investigational Pharmacy Code AdminDateDateDate Study Drug Administered AdminTimeTimeTime Study Drug Administered SzStopPreHospYes/NoDid seizure stop during pre- hospital course? SzStopPreHosp Time TimeTime seizures stopped during pre-hosp course (blank if seizure did not stop) HospArrTimeTimeHospital Arrival Time HospArrSzActYes/NoWas there continued Seizure Activity on Hospital Arrival? Check against SzStopPreHosp HospArrGCSVIntegerVerbal GCS on Hospital Arrival (blank if seizure continued) Between 1 and 5

Methods: Design-Nested double cohort study. Setting-Kaiser Subjects-Infants with neonatal jaundice and randomly selected non-jaundiced infants Predictor Variable-Presence or absence of jaundice Outcome Variable- Neuropsychological score (ranging from 55 to 145) at age 5 Analysis- ? JIFee Jaundice and Infant Feeding Study Newman, T. B., P. Liljestrand, et al. (2006). "Outcomes among newborns with total serum bilirubin levels of 25 mg per deciliter or more." N Engl J Med 354(18):

Infant Jaundice Study Data 1.Approximately 400 children 2.5 examiners (doctors) 3.Approximately 700 neuropsychological examinations, measuring weight, height, and “NPScore” (IQ) 4.Some children to be examined more than once 5.No examiner to see the same child twice 6.If child died before age 5, store age and circumstances of death

Infant Jaundice Study Table of Subjects Row = Individual Infant Columns = ID#, Name, DOB, Sex, Jaundice. If one set of measurements per subject, put measurements in subject table. This is a single-table database. Table of Study Subjects

Demonstration: Creating a Data Table Label columns and enter rows of data in datasheet view Where is predictor on data collection form?

Demonstration: Data Dictionary Table design view: field (=column) names, data types, definitions, validation rules (More on data types, free-text vs. coded responses, later)

Acceptable table showing one set of exam results per participant. (BabyExamForFigure3)

Demonstration Disallowed values Duplicate primary keys This automatic error checking and data validation IS why you need to enter your data into a computer; it is NOT why you need a relational DBMS. Many single- table products (Filemaker Pro, SAS FSP, even Excel) can do error checking and data validation.

Demonstration: Same Table in Excel, Stata Excel Stata Etc Rows = Records = Entities Columns = Fields = Attributes Access and Stata have a special row at the top for column headings (=field names); Excel just uses the first row.

Normalization

Table of Study Subjects Row = Individual Infant Columns = ID#, Name, DOB, Sex, Jaundice If some infants have more than one exam, what do you do? Table of Study Subjects

Undesirable table showing multiple exam results per study participant. (BabyExamForFigure4)

Demo Find highest IQ Score Find all exams done in April

Common Error If you find yourself creating multiple columns for the same measurement, e.g., Date1, Score1, Date2, Score2, Date3, Score3, … Or if your table is more than about 30 columns wide, –It is time to restructure your table.

Undesirable table with participant-specific data duplicated for each exam. (Note problem with Helen’s DOB.) (ExamBabyForFigure5)

Demo Find highest IQ Score Find all exams in a particular month What is Helen’s birth date? What happened to Alejandro, Ryan, Zachary, and Jackson?

If some infants have multiple exams, “normalize” the records into two tables, one for subjects and one for examinations. Normalization

Data normalized into two tables: one (“Baby”) with rows comprising subject- specific information; the other (“Exam”) with rows comprising exam-specific information. Note that Helen can only have one birth date. Subjects with no exams, e.g. Alejandro, still appear in the database. “SubjectID” functions as the primary key in the “Baby” table and as the foreign key in the “Exam” table.

Figure 7. Relationships diagram showing the one-to-many relationship between the table of subjects (“Baby”) and the table of measurements (“Exam”).

Demonstration Inability to create integrity violations with normalized tables. This IS why you need a multi-table relational DBMS.

Lab Results Occasionally, the subjects had blood tests. Robert had a CBC on 1/30/2010. Helen had a CBC on 1/30/2010, LFTs on 2/28/2010, and a CD-4 count on 3/31/2010.

LabResultQry

Undesirability of Storing Calculated Values Store raw data, not calculated fields, e.g., store dates and times; calculate intervals. Storing a patient’s birth date allows calculation of his or her exact age on the date of a particular measurement.

Figure 15. Storing calculated fields such as “AgeInMonths” is undesirable. What if the birth date for SubjectID 2322 (Helen) is corrected in the “Baby” table?

Queries

Select Queries Select queries (aka “Views”) organize, sort, filter, and display data. Queries use Standard Query Language (SQL), but you don’t have to learn it, because of graphical query design tools. A query can join data from two or more tables, display only selected fields, and filter for records that meet certain criteria.

Demonstration Age in months and BMI at exam of subjects who were examined in January and February of QueryDemo

Select Queries Produce “Table-Like” Results Note that the result of a select query that joins two tables, displays only certain fields, selects rows based on special criteria, and calculates age and BMI still looks like a table in datasheet view. But, remember that it is a dynamic “view” of data from the underlying tables.

“Action Queries” Change Data 1)Update Query -- changes the values of specific fields in existing records 2)Append Query -- adds new records (rows) to a table 3)Delete Query -- deletes records from a table

Front End or Interface On-screen forms

Advantages of On-Screen Forms Data keyed directly into the computer data tables without a transcription step Include validation checks and provide immediate feedback when a response is out of range Incorporate skip logic

Standard Data Entry Conventions Several conventions for data entry and display have developed over time. Most users of screen forms have come to expect them subconsciously. mutually exclusive, collectively exhaustive choices are displayed as an “option group” consisting of several different “radio buttons”. choices which are not mutually exclusive are displayed as check boxes. N.B. An “option group” of mutually exclusive choices is a single column or field. A group of N check boxes represents N yes/no fields.

Use check boxes when options are not mutually exclusive. (5 fields) Use radio buttons when options are mutually exclusive. (1 field) Computer chart abstraction form showing two common data entry conventions.

Demonstration Option group for examiner’s medical specialty MasterRaceAsFieldList, MasterRaceAsOptionGroup, MasterRaceAsAllThatApply

On-screen vs. paper forms Minimize the extent to which study measurements are recorded on paper forms. Enter data directly into the computer database or move data from paper forms into the computer database as close to the data collection time as possible. When you define a variable in a computer database, you specify both its format and its domain or range of allowed values. Using these format and domain specifications, computer data entry forms give immediate feedback about improper formats and values that are out of range. The best time to receive this feedback is when the study subject is still on site. Can only monitor data for outliers, systematic differences between data collectors or study sites, and study progress (I.e., query the data) once the data are in the computer. You can always print out a paper copy of the screen form or a report of the exam/interview results once the data are collected.

Outline Housekeeping Data Tables –Rows = Records; Columns = Fields Normalization of Data Tables Queries Front End or Interface/On Screen Forms

Don’t Forget Lab 1 next Tuesday 1/12/2010 View the Learn MS Access 2000 Video Username: ucsfdbclass Password: access2000 (We can also loan you the video on CD.) Start thinking about your study database and Assignment 4/Final Project.