Streamlining Specimen/Label Shipment Process

Christina Carty and Elizabeth Spence VA Cooperative Studies Program Coordinating Center, Perry Point, Maryland

ABSTRACT A primary challenge of the Perry Point data management staff is to provide a system for tracking the collection and transfer of samples between clinical sites and the specimen repository. The tracking system allows us to validate the case report forms (CRFs) that contain the label information, determine eligibility for shipment, provide notification to the clinical sites regarding specimens cleared for shipment, and produce reports for auditing.

Base SAS® was used to design the four step tracking system and encompasses a variety of programming techniques including macros, Output Delivery System (ODS), PROC REPORT, and email capabilities. The validation process includes a check for duplicate labels, and verification of the label numbers reported on the CRFs. Eligibility is determined when all CRFs have passed standard edit checks and all four periods are accounted for. The third step is an automated report creation and email notification process that informs clinical sites about specimens cleared for shipment. Finally, a series of audit tracking programs were developed to produce reports for use by the clinical sites and the study chairman’s office.

Collectively, the various programs yield a progressive and streamlined mechanism for accomplishing a myriad of tasks. OVERVIEW The Department of Veterans Affairs Cooperative Studies Program Coordinating Center (CSPCC) at the Perry Point, Maryland VA Medical Center is an administrative, data management, and statistical coordinating center for both VA and non-VA medical research clinical trials (studies). Faced with the challenge of tracking and auditing the collection and transfer of specimens in an ongoing clinical trial, the Perry Point data management staff designed and developed a system utilizing SAS version 8.2 for both Microsoft Windows and ALPHA OpenVMS. We created and maintain a master label database consisting of four randomly assigned label numbers (observations) for each patient identifier (PID). The pre-assigned labels are distributed to sites for shipping specimens to the repository and reporting on CRFs. Each patient is assigned four sets of five labels, one set of five for each sample drawn. Two of the labels are used for cryovials, one label contains the PID which is affixed to the CRF, one label contains the pre-assigned specimen label number and is affixed to the CRF, and the fifth label is a spare which can be used if necessary to label the cryovial or CRF. Upon electronic retrieval of the CRF at the coordinating center we perform a number of checks to validate the PID and label information. The CRF is then subject to our standard internal editing process. Eligibility for clearance to ship is dependent upon resolution of these queries. Once all CRFs have passed the edit checks and all other issues have been resolved, a subject’s periods are counted and the specimens are cleared for shipment. A macro is used to scan the master dataset and create a work dataset for each site that contains specimens (observations) cleared for shipment. Based on positive dataset attributes the macro then automatically generates and emails a report to each site. In addition, a report is generated that includes all sites’ specimens (observations) cleared for shipment that is emailed to the chairman’s office for review. PROC REPORT is used again in the audit tracking process. Reports include listings of specimens shipped to the laboratory that were not cleared for shipment by Perry Point, and listings of specimens cleared to ship which have not been received at the laboratory. STEP 1 - VALIDATION Fortnightly the data is downloaded to the coordinating center and validation checks are performed to determine if duplicate labels or invalid label numbers were reported on the CRF. If inconsistencies are found in-house procedures are followed to rectify these discrepancies prior to the quarterly update of the master label database. These checks provide a mechanism to closely monitor the collection of specimens to assure validity.

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On a quarterly basis we perform these same checks and update the CRF database by flagging each observation to ascertain eligibility for shipment. In addition, the PID from the CRF is used to update the master label database with the PID assigned (PID_ASSGN). Below is an example of the code generated to accomplish validity checks on a quarterly basis:

/* Check for duplicate label numbers */; DATA TMPSTUDY.LABXX FORMXX; SET STUDY.FORMXX; BY BLDLABE2; if BLDLABE2 > ' ' AND (not first. LDLABE2 or not last.BLDLABE2) then do; B IF eligship = . THEN eligship=5; put ///// 'Duplicate label, label =' BLDLABE2 /////; END; IF reeddate = . and eligship = . THEN OUTPUT FORMXX; *obs on edit and ineligible to ship*; ELSE OUTPUT TMPSTUDY.LABXX; *obs to perform validity checks*; /* Check for invalid label numbers */; DATA FMXX (DROP=PID LETCODE MATCH); SET FORMXX; /* Temporarily rename some variables */; PID_ASSGN=PID; LETCODE_ASSGN=LETCODE; LABEL=BLDLABE2; ORIG_MATCH=MATCH; RUN;

PROC SORT DATA = FMXX; BY LABEL; RUN; DATA REPORT (KEEP=PID LETCODE LABEL PID_ASSGN LETCODE_ASSGN PERIOD BLDDRAW DRAW_DT MATCH ELIGSHIP) ORIG.LABELS (KEEP=CENTER PID LETCODE LABEL PID_ASSGN MATCH) NEWFMXX (DROP=PID LABEL LETCODE); MERGE ORIG.LABELS(IN=A) /*master label database*/ FMXX(IN=B); BY LABEL; IF B AND BLDDRAW = 0 AND BLDLABE2 = ' ' THEN DO; ELIGSHIP=1; MATCH=0; END; IF B THEN DO; IF (BLDDRAW=1 AND BLDLABE2 > ' ') THEN DO; IF PID NE PID_ASSGN THEN MATCH =9; /*Non-matched label*/ ELSE DO; MATCH=1; ELIGSHIP=1; /*Matched label*/ END; END; END; ELSE IF eligship = 1 THEN MATCH=ORIG_MATCH; IF B THEN OUTPUT NEWFMXX; if A and last.label then output ORIG.LABELS; if b and ^ a and bldlabe2 > ' ' then do; put ///// 'FORM XX LABEL NOT IN LABEL DATABASE ' PID_ASSGN= LABEL= /////; output report; RUN;

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DATA FORMXX (RENAME=(PID_ASSGN=PID LETCODE_ASSGN=LETCODE)); SET NEWFMXX; RUN; DATA FORMXX; SET FORMXX TMPSTUDY.LABXX; RUN; proc sort data = formXX OUT=STUDY.FORMXX; by center id; run;

STEP 2 – ELIGIBILITY The data coordinating center has developed an in-house data management system using SAS, which includes cleaning and editing raw data. The cleaning process includes cross checking data points and verifying that data values are within specified valid range. In the event the data is not valid, a standard procedure is followed to mark observations (a re-edit date is set) to alert the data source as well as the end users the status of the observation. These processes will be performed under the current standard operating procedures developed within the coordinating center. Those observations containing invalid data will not be included in the dataset referred for further testing for shipment eligibility. According to study procedures all four periods of data collection must be reported on the CRF’s (for the entire PID) to be eligible for shipment. Shown below is the code to accomplish this:

DATA period (KEEP=PID no_rec tot_elig); SET STUDY.FORMXX (WHERE=(SHIP_DATE = . AND ELIGSHIP=1)); BY PID period; retain count date1 date2 date3 date4 ELIG; format date1 date2 date3 date4 mmddyy10.; ** count = accumulator of periods for patient **; ** tot_elig = sum of ELIGSHIP for patient **; ** no_rec = sum of count **; if first.pid then do; count=0; elig=0 ; date1=.; date2=.; date3=.; date4=.; end; if ELIGSHIP = . then ELIGSHIP = 0; if period = 1 then do; date1=datecomp; count + 1; elig+ELIGSHIP; end; if period = 2 then do; date2=datecomp; count + 1; elig+ELIGSHIP; end; if period = 3 then do; date3=datecomp; count + 1; elig+ELIGSHIP; end; if period = 4 then do; date4=datecomp; count + 1; elig+ELIGSHIP; end; if last.pid then do; no_rec=count; TOT_ELIG = ELIG; output; end; run;

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data STUDY.FORMXX (drop= n_rec t_elig) ; merge STUDY.FORMXX(in=a) period(rename=(tot_elig=t_elig no_rec=n_rec)in=b); by pid; if a then do; if t_elig GE 0 then tot_elig = t_elig; if n_rec GE 0 then no_rec = n_rec; if BLDDRAW=1 AND BLDLABE2 > ' ' and ship_date = . and tot_elig=4 and no_rec=4 then ship_date=today(); if eligship = 1 and match = . then status = 1; *No specimen drawn*; if eligship = 1 and match = 0 then status = 1; if eligship = 5 and match = . then status = 2; *Duplicate label*; if eligship = 1 and match = 1 then status = 3; *Matched label*; if eligship = 1 and match = 9 then status = 4; *Non-match label okay to ship*; if eligship = . and match = 9 then status = 5; *Non-match label pending verification*; if eligship = . and match = . then status = 6; *Record failed edit*; if eligship = . and match = 0 then status = 6; output; end; run;

STEP 3 – COMMUNICATION Once validation is attained and eligibility is established it is necessary to communicate to sites the results of these processes. SAS allows us to simplify this step by using macro programming, PROC Report, and ODS. Automated communication is achieved via SAS’s email capabilities. Individual site names and email addresses are maintained in a central administrative database. The database is used to created formats for labeling reports and emailing. Macro programming is used to cycle through the site numbers to create work datasets for each site, %sysfunc is used to determine if observations exist and if so the macro continues by generating emails containing the individual sites standard report. Within the macro, PROC Report and ODS create the PDF files that are emailed to the individual sites as an attachment. These reports have been customized and will be used by the sites as a manifest when shipping specimens to the central repository. Also within the same macro, PROC Report and ODS generate a rich text file (RTF) containing a combined report that is emailed to several core administrative staff. The code below demonstrates this step of the process:

%macro byctr(ctr=); data newform&ctr; set STUDY.FORMXX; newvar = center; serum1 = .; serum2 = .; where center = &ctr and (ship_date = TODAY()) and date_received = . ; email = put(center,email.); call symput('addy',email); run; %let dsid=%sysfunc(open(newform&ctr)); %let num=%sysfunc(attrn(&dsid,nobs)); %let rc=%sysfunc(close(&dsid)); %if &num > 0 %then %do; ods pdf(id=&ctr) file="X:\study\program\label_&ctr..pdf " style=sasweb; proc report data = newform&ctr headline headskip split='/' nowd; by center newvar;

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format center center.; format newvar z3.; title 'STUDY NAME'; title2 'Clinical Site #BYVAL(center) - #BYVAL(NEWVAR)'; title3 'Cryo Vial cleared to ship the following label numbers to the '; title4 'ABC Repository, Inc.'; TITLE5 "Report date - &SYSDATE"; column PID LETCODE PERIOD DRAW_DT BLDLABE2 SERPLA SERUM1 SERUM2; define pid / group id 'Patient/ID Number'; define letcode / group id width=7 'Letter/Code'; define period / width=40 'Sample Period' left f=period.; define draw_dt / width=12 'Date/Specimen/Drawn'; define serpla / width=8 ' Specimen /Processed As' center f=serpla.; define serum1 / width=6 'Serum 1'; define serum2 / width=6 'Serum 2'; define bldlabe2 / width=6 'Form/Label' style(column)={font_weight=bold}; footnote1 'DATE SENT TO ABC REPOSITORY: _____________________________________'; run; ods pdf(id=&ctr) close; filename STUDYF email "&addy" subject="STUDY Center &ctr: Blood specimens cleared for shipment" attach=("x:\study\program\label_&ctr..pdf"); data _null_; file STUDYF; put '!EM_FROM!' 'your.email@xx.gov'; put '!EM_SENDER!' 'jane.doe1@xx.gov'; put '!EM_reply!' 'jane.doe1@xx.gov , jane.doe2@xx.gov'; put "Good day, Attached is a listing for your center of blood specimens cleared for shipment."; put 'If you have any questions or problems, please feel free to contact Jane Doe at 123-456-7890, ext. 4321'; put //; put 'Have a wonderful day!'; put ///////////////; put '______________________________________'; put 'CONFIDENTIALITY NOTICE'; put /; put 'This email message, including any attachments, is for the sole use of the intended recipient(s) and'; put 'may contain confidential or proprietary information which is legally privileged. Any unauthorized'; put 'review, use, disclosure, or distribution is prohibited. If you are not the intended recipient, please'; put 'promptly contact the sender by reply email and destroy all copies of the original message.'; run; %end; %mend byctr;

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ods listing close; ods rtf file= x:\study\program\all_sites.doc ' style=sasweb; ***** Add new sites (if any) to BYCTR macro *****; %byctr(ctr=001); %byctr(ctr=002); . . . . %byctr(ctr=199); %byctr(ctr=200); run; ods rtf close; title; footnote; run; filename STUDYFS email ("john.smith@xxx.edu" "jane.doe@xxx.com" "john.smith1@xxx.gov" "jane.doe2@xxx.gov") subject="STUDY: All Sites blood specimens cleared for shipment" attach=("x:\study\program\all_sites.doc"); data _null_; file STUDYFS; put '!EM_FROM!' 'your.email@xx.gov'; put '!EM_SENDER!' 'jane.doe1@xx.gov'; put '!EM_reply!' 'jane.doe1@xx.gov , jane.doe2@xx.gov'; put "Good day, Attached is a listing by center of blood specimens cleared for shipment."; put 'If you have any questions or problems, please feel free to contact Jane Doe at 123-456-7890, ext. 1234'; put //; put 'Have a wonderful day!'; put ///////////////; put '______________________________________'; put 'CONFIDENTIALITY NOTICE'; put /; put 'This email message, including any attachments, is for the sole use of the intended recipient(s) and'; put 'may contain confidential or proprietary information which is legally privileged. Any unauthorized'; put 'review, use, disclosure, or distribution is prohibited. If you are not the intended recipient, please'; put 'promptly contact the sender by reply email and destroy all copies of the original message.'; run;

STEP 4 – AUDITING In all clinical research a means of quality control must be implemented to validate the integrity of the data collected. Tracking reports are the method of choice to perform the auditing functions required for this project. When data is received fortnightly, internal checks are performed to produce reports for in-house auditing. The reports consist of listings of duplicate label numbers received, listings of label numbers received that do not exist in the master label database, and listings of label numbers that do not match the pre-assigned PID. Quarterly a specimen database is downloaded from the central repository. The specimen database is used to update the master data with the date specimens were committed into the central repository database. Several reports are generated from this transaction including a report to the study chairman’s office listing specimens shipped by the clinical sites that were not eligible to be shipped. In the event a label number is received in the specimen database that does not have a corresponding CRF or when duplicate CRFs exist in the master database the data is separated

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into a temporary database. That database is then used during the next quarterly update by appending it to the specimen database. In addition, reports are produced for the clinical sites which track shipments that were cleared and not received at the central repository. The clinical trial that these processes apply to is currently on-going and the auditing process continues to evolve. Future development will involve other types of automated tracking such as monitoring the receipt of specimens at the central repository, and tracking the specimen shipments from the central repository to the specimen lab. We will also provide the core lab with analysis results received from the specimen lab. CONCLUSION Perry Point has been successful in implementing a system that allows us to monitor the collection and transfer of specimens between the clinical sites and the laboratory. Quality control is a priority in this endeavor and this system provides the mechanism for achieving that goal. ACKNOWLEDGEMENT The author’s would like to express their appreciation to the following people for their assistance in this paper: Cynthia Zender, SAS Institute Inc. R. Anne Horney, Department of Veterans Affairs, Perry Point Cooperative Studies Coordinating Center This work was subcontract by a cooperative agreement between the National Heart Lung, and Blood Institute (NHLBI) award number UO1HL074825 and the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) data coordinating center. CONTACT INFORMATION Your comments and questions are valued and encouraged. Contact the authors at:

Christina Carty CSPCC (151E) VA Medical Center, P.O. Box 1010 Perry Point, MD 21902 Phone: 410-642-2411, ext. 5354 Fax: 410-642-1156 Email: Tina.Carty@va.gov

Elizabeth Spence CSPCC (151E) VA Medical Center, P.O. Box 1010 Perry Point, MD 21902 Phone: 410-642-2411, ext. 5308 Fax: 410-642-1156 Email: Elizabeth.Spence@va.gov SAS and all other SAS Institute Inc. product or service names are registered trademarks or trademarks of SAS Institute Inc. in the USA and other countries. ® indicates USA registration. Other brand and product names are trademarks of their respective companies.

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