Patient profile is a listing of all (or selected, sometime) data for individual subject in clinical study organized by time. Subject can be patient or healthy volunteer, though it is referred as Patient Profiles. Patient profiles are optional in submission to FDA.
However, patient profiles were recommended to submit in pdf file in CRT (Case Report Tabulation) to FDA previously (as per guideline for Providing Regulatory Submissions in Electronic Format, 1999). Patient profiles are not expected in submission if data are CDISC-SDTM compliant; since FDA has powerful tool (like PPD Patient Profiles software) to create patient profiles from SDTM data (unless specifically requested). Still this listings (patient profiles) have different users in the company with different purpose. For example, patient profiles can be generated for-
• Data Cleaning: Used by statistician, data manager, SAS programmer, CRA, medical team to review data before database lock.
• Internal Review: Data Safety Monitoring Board (DMSB)/Physician: Used to review the data and safety of subject during clinical trial.
• Narratives: Used by medical writers to generate patient safety narratives.
Patient Safety Narratives (or just narratives):
ICH-E3 guideline for Clinical Study Report calls for patient narratives in section 12.3.2. These narratives can be part of CSR or can be submitted separate document(s) depending on number of narratives in the study (or submission). Narrative is an account of all events in plain English (i.e. narration, written by medical writer) encountered in subject's course of clinical trial in chronological order. This is organized and written in such a way that it conveys information to reviewer about various clinical events (informally, we can say whole story of subject). Patient narratives are part of safety data submitted to regulatory authority for all phases of clinical trial.
As a SAS programmer, you may come across various roles; one of them can be to provide data to create patient narratives. This data is generally provided in form of SAS dataset or it can be in form of listing output report. Types and structure of datasets/listing for patient narratives varies from company to company.
Eligible subjects for narrative:
Generally, it is written for following subjects (as per ICH E3).
• Each subject whose death was reported in study
• In addition, subjects who experienced serious adverse event(s)
Those subjects who encountered other significant adverse events (or laboratory abnormal finding) of special interest because of clinical importance for particular study
The content of a narrative:
ICH E3 guideline in section 12.3.2 on page 24 says, a patient narrative should include following information-
’’the nature and intensity of event, the clinical course leading up to event, with an indication of timing relevant to test drug/investigational product administration; relevant laboratory measurements, whether the drug was stopped, and when; countermeasures; postmortem findings; investigator's opinion on causality, and sponsor's opinion on causality, if appropriate’’ (from ICH E3 guideline, Page 24).
To extract meaningful information from narrative, the following data should be also included as per ICH E3 guideline.
• Age and sex of patient; general clinical condition of patient, if appropriate
• Disease being treated (if the same for all patients this is not required) with duration (of current episode) of illness
• Relevant concomitant/previous illnesses with details of occurrence/duration
• Relevant concomitant/previous medication with details of dosage
• Test drug/investigational product administered, drug dose, if this varied among patients, and length of time administered
What is expected from SAS Programmer?
SAS Programmer has significant contribution in creation of patient narratives by providing key data information to the medical writer. This can be in form of dataset or listings depending on company and their requirements. Generally, big data sets specifications are provided. However, thorough understanding of requirement is very essential. Once the datasets are created, this datasets are feed into standard tool of narrative to create narrative (text part) with data. Thus, the role of the programmer in narrative writing process is to provide all the data medical writer needs.
When creating such datasets or listings, briefly, programmer might come across following challenges—
• Decide no. of subjects for narratives: It can be based on companies’ criteria for narratives (may be similar to ICH E3 guideline) for study.
•Get the specifications of datasets/listing to create: You may need to know what expected structure of final narrative datasets/listings is. Sometime you may be given previous study’s narratives as reference.
•Specification of narrative datasets and information may vary based on investigational drug, therapeutic area etc.
•During your programming, you need to bring different data from different domains like AE, LB, DM, MH, CM, EX, VS, EG etc. for each subject/narratives (per subject).
•It should be arranging in order of chronological order for the listing.
•There should be standard macro for bringing data at one place in company. Please use those for convenience. If needed, please create new macro for repetitive work.
Process of narrative creation:
The process of creating narratives can be started before database lock or after database lock. In pre-database lock, once draft narrative is created, you have to update final data after database lock. Hence, it consumes more time to create it. However, this approach helps when there are many narratives to be created in a project. In post-database lock, narratives are created from final data. So, narratives can be created in short time.
Medical writer can use various data source like CRF pages, SDTM, ADaM, pharmacovigilance database, data clarification form (DCF) etc. Hence, it is imperative to do reconciliation of all databases to avoid any discrepancy in the narrative and submitted data.
It is a little different task from regular work, however, base SAS, Macro and Proc SQL skills would be enough to generate narratives as per requirements.
Guidance for Industry - Providing Regulatory Submissions in Electronic Format — NDAs, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), IT 3, January, 1999.
Peterson, Terek, and Sanjiv, Ramalingam. "Operational Uses of Patient Profiles ... Even in an ECTD and SDTM World." PharmaSUG AD21 (2010): n. pag. Web. 7 Dec. 2015.
Hantsch, J J, and Janet Stuelpner. "One at a Time; Producing Patient Profiles and Narratives." SAS Global Forum 211 (2012): n. pag. Web. 7 Dec. 2015.
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