I know what you’re thinking. You can manage your bank account online, so why can’t you enter your study data online, right? Well, now you can, with iDataFax electronic data capture!
What is iDataFax Electronic Data Capture?
iDataFax is a software program that allows sites to enter case report form (CRF) data directly into SCHARP’s clinical data management system (CDMS) via electronic data capture, or EDC. Read more…
As the Statistical Data Management Center for the HVTN, the Statistical Center for HIV/AIDS Research and Prevention (SCHARP) manages data of many different types and from different sources. One way the Network accesses that data is via the Atlas web portal. It serves a broad range of user groups within the HVTN by hosting not only data but also reports and documents, as well as tools for uploading and interacting with the data.
The amount of content posted on the HVTN’s Atlas site has slowly grown since its inception, and had reached a point where a major reorganization and re-visioning of the site was required for it to remain effective. SCHARP Information Systems, in partnership with LabKey Software (the developer of the platform used by Atlas) recently completed a project to update the site. During the redesign process we sought input from various users and performed usability testing, incorporating the results into the final design. Read more…
You may have heard someone talking about it in a breakout session at the last HVTN Full Group Meeting. Or maybe you remember seeing something about it in a grant application…What was it called again…CDISC?
CDISC sounds like it could be one of those popular TV dramas, involving an international organization working with major corporations on a mysterious mission that no one seems to understand. But what’s CDISC really about?
What is CDISC?
CDISC, or the Clinical Data Interchange Standards Consortium, is an international organization, and yes, it does have a lot of big names involved. CDISC members and sponsors are volunteers who come from pharmaceutical companies, clinical research organizations, and academic institutions. They are joined together in a common mission — to develop and support harmonized standards for collection, exchange, submission, and archival of data from clinical studies. Sounds intriguing, right?
CDISC standards are designed with maximum accessibility in mind. To encourage organizations to adopt them, the standards are vendor-neutral, platform-independent, and freely available (on cdisc.org). CDISC has been developing a comprehensive set of models — a collection of concepts and rules used to structure and define data. (Models also serve to provide valuable context to aid in communication about the data between organizations.) Models have been developed to cover each stage in the lifecycle of a study, starting with the protocol, and going through data collection, data tabulation (for submission to regulatory authorities), analysis, and data exchange. Figure 1 shows an overview of the CDISC models for data standards at each study stage.
The CDISC Models
CDISC models (known by their acronyms, eg, CDASH, SDTM, ADaM) focus on different study stages and uses of the data. The most important CDISC model for SCHARP and our sponsors is the SDTM — Standard Data Tabulation Model. SDTM is used for regulatory submission. This model defines a standard structure where the data is put into tables organized within a set of categories (interventions, events, and findings). These tables are designed to maximize compatibility with common software tools used by regulatory authorities, such as the FDA, for reviewing the data.
The Clinical Data Acquisition Standards Harmonization (CDASH) model standardizes the way data is collected to facilitate the generation of SDTM tables. You can think of CDASH as building in the conventions for SDTM further upstream, during data collection, to make the creation of the SDTM tables more efficient. The Analysis Data Model (ADaM) is a set of guidelines and examples for analysis datasets used to generate statistical results for submission to FDA. ADaM specifies a standard for the data structure and associated metadata for analysis datasets, and defines the fundamental principles that apply to all analysis datasets.
Why Adopt CDISC at SCHARP?
Having managed the data for over 175 studies, SCHARP has developed its own set of standards for use across the NIAID networks’ (HVTN, HPTN, MTN, and IMPAACT) studies. Ultimately, adopting a more broadly accepted model, utilized by a larger community, is beneficial not only to SCHARP, but also to the networks and sponsors we support.
One of the main goals of getting organizations to adopt data standards is to facilitate cross-study comparisons by establishing and applying global standards for data elements and structures. As statistical and data management center, we also hope it will help make database development during set up of a new study more efficient.
CDISC has been one of a number of models for data standards which have gained recognition over the last several years. However, more recently, the FDA has indicated a preference for the CDISC model. Although not yet an official requirement, the FDA is currently requesting that data submissions be compliant with CDISC standards.
How is Data Converted to SDTM?
When a sponsor plans to submit a study to a regulatory authority, like the FDA, SCHARP converts the final study data into the SDTM format, mapping data elements to specified SDTM variables and reorganizing the data into specified categories, referred to as observation classes and domains. We’re essentially telling the story about that study, by providing details in a predefined way.
To begin the conversion to SDTM tables, the SCHARP conversion team goes through all the study data and determines the appropriate categories (observation classes and domains) for the data. Next, the required SDTM variables for those domains are identified and mapped to the study data from the original datasets (case report forms, assay data from the labs, and questionnaire data from online survey tools) and to additional study-related metadata from other sources (eg, normal ranges for lab values). Figure 2 shows an example of how the study data and metadata for local safety lab data are mapped onto the SDTM variables.
Once the mapping specifications are defined, automated mapping programs are generated that use those specifications to convert the original data sets into the SDTM data tables in SAS format. A final document, called a Define File, is generated in XML (with hyperlinks) to summarize which domains are included and to show how the data was mapped.
SCHARP’s CDISC Plan
To be CDISC compliant means to follow the rules and conventions defined by the CDISC models. Because there are different CDISC models (eg, CDASH, SDTM, ADaM) that focus on different aspects of the data, it’s possible to be compliant for one CDISC model, but not follow all the models.
SCHARP’s goal is to be SDTM and CDASH compliant for new studies opening December 2014 or later, after which data to be analyzed or submitted to the FDA could be requested in SDTM format at any point during or following the trial. In the meantime, the plan is to have processes in place by the end of this year, should a sponsor request an unplanned SDTM conversion for an existing study.
At the request of the MTN, SCHARP is taking the first step toward these goals by piloting the conversion process on an existing MTN study and creating mapping specifications for all our standard forms. This conversion exercise will provide valuable experience that will be applied to the HVTN and other NIAID networks. A new version of DataFax (the data capture / management system used by SCHARP) is expected this year that will provide additional support for SDTM and CDASH standards.
As SCHARP gains more experience with CDISC and the process for converting studies to SDTM, we are reminded that each study has its own interesting story to tell…and most of them are mysteries. Who knows, maybe they’ll make a miniseries about them!
Drienna Holman is SCHARP Program Manager – Special Projects.
The HIV Vaccine Trials Network presented its latest work throughout the AIDS Vaccine 2013 conference in Barcelona, Spain. This guide lists HVTNrelated content at the conference, with links to webcasts/ePosters if available.
Satellite Session: Thursday, October 10, 2013, 15h00-17h00
Meta-Analysis of HVTN Efficacy Studies with Adenovirus Vectors
The HVTN has conducted a series of efficacy trials involving recombinant adenovirus type 5 (Ad5)-containing vaccines. Despite high rates of immunogenicity, none of the trials found a reduction in the primary or secondary endpoints of reducing HIV acquisition or post-acquisition viral load. This session will present overviews and updates on the individual trials and a meta-analysis of the three trials, to prompt discussion regarding the findings and future directions of adenovirus-based vaccines for HIV and other diseases.
Introduction – Larry Corey
Immunogenicity of Ad5 Based Vaccines – Julie McElrath and Georgia Tomaras
Overview and Update of the Step Study (HVTN 502) – Susan Buchbinder
Overview and Update of Phambili (HVTN 503) – Glenda Gray
Overview and Update of HVTN 505 – Scott Hammer
Meta-Analysis of HVTN Experience with Adenovirus Vectors – Peter Gilbert
Invited Guests Presenting HVTN Data:
- Opening Session: Magda Sobieszczyk
- Roundtable Discussion, Clinical Trial Follow-up and Retention: Glenda Gray, Scott Hammer, and Susan Buchbinder
- Symposium 1, Innate Immunity: Dan Zak
- Symposium 4, Viral Vaccine Vectors: Harriet Robinson
Oral abstract Presentations:
- Hancock G, Yang H, McMichael AJ, et al. Effective antiviral CD8+ T cells responses are rare in HIV-positive Step & Phambili study participants but are targeted to low entropy viral epitopes.
- Williams WB, Jones K, Liu P, et al. Antibody repertoire induced by the multiclade (Env A,B,C) HIV-1 DNA prime, rAd5 boost VRC vaccine.
Poster Discussion Presentations:
- Deschamps MM, Zorrilla C, Morgan C, et al. Feasibility of enrolling female commercial sex workers at high risk of HIV infection for HIV vaccine trials in the Caribbean.
- Frank I, Grunenberg N, Hural J, et al. Enhanced HIV-specific CD8+ T cell responses following polytopic administration of VRC rAd5 gag-pol/env A/B/C in HIV-uninfected healthy adults.
- Huang Y, Duerr A, Moodie Z, et al. Immune-correlates analysis of the Step HIV vaccine efficacy trial – a post-hoc analysis of HIV-specific and non-specific cellular immune responses.
Adamson B, Fuchs J, Johnson P, et al. Development of an early stage investigator scholar program for preclinical researchers.
Adamson B, Hertz T, Duerr A, et al. Baseline predictors of immunogenicity in HVTN 204.
Adamson B, Wakefield S, Flood D, et al. HVTN mentored research program for black and Latino/a medical students increases intent to pursue a career in HIV/AIDS vaccine research.
Cerwensky K, Laher F, Otwombe K, et al. Predictors of HVTN 503 MRK AD5 HIV-1 gag/pol/nef vaccine-induced immune response.
Coombs A, McFarland W, Ick TO, et al. Long-chain peer referral to recruit black MSM and black transgender women for an HIV vaccine efficacy trial.
De Rosa SC, Frahm N, Diaz G, et al. No increase in activated T cells and limited increase in adenovirus-specific T cells in colon and rectal mucosa following HIV-1 DNA/rAd5 immunization.
Poster Presentations (cont.):
Deschamps MM, Joseph P, Severe K, et al. Strategy to conduct vaccine trials: The GHESKIO experience.
Ducar C, Smith D, Stirewalt M, et al. Benefits of a comprehensive, semi-automated quality program for cryopreserved PBMC covering 29 globally distributed clinical trials sites.
Flood D, Wallace M, Racow K, et al. Attracting, equipping and retaining young investigators in HIV vaccine research in South Africa.
Fuchs JD, Frank I, Kochar N, et al. A recombinant vesicular stomatitis virus (rVSV) HIV-1 gag vaccine is safe and immunogenic in healthy, HIV-1 uninfected phase I trial participants.
Hammer S, Sobieszczk M, Janes H, et al. HVTN 505: Efficacy of a multi-gene DNA prime/recombinant adeno 5 vector boost vaccine in men & transgender women who have sex with men.
Hancock G, Yang H, Frahm N, et al. The antiviral efficacy of CD8+ T cells in early HIV-1 infection is dependent on targeting of low entropy regions of the viral proteome.
Heit A, Schmitz F, Moore M, et al. HVTN-tested candidate HIV vaccines induce early, antigen-specific plasmablast- and Tfh-like responses in peripheral blood.
Hural J, Walsh S, Moodie Z, et al. Vaccination with heterologous HIV envelope sequences and heterologous adenovirus vectors increases T cell responses to conserved regions: HVTN 083.
Karuna S, Andrasik M. Transgender participants in phase 1-2a trials of the HIV Vaccine Trials Network (HVTN): A descriptive analysis.
Lemos MP, Lama JR, Karuna ST, et al. In men at risk of HIV infection, antibodies can reach the human foreskin epidermis at ratios similar to those in blood.
Lemos MP, Karuna ST, Lama JR, et al. The inner foreskin of healthy men resembles inflamed epithelium and has features of a compromised skin barrier.
Morris L, Mkhize NN, Hermanus T, et al. Boosting antibody responses with gp140 protein two years after DNA/MVA priming: Results from the HVTN 073E Phase I vaccine trial.
Seaton KE, Yates NL, Williams WT, et al. Human HIV-1 vaccine induced antibody durability and Env IgG3 responses.
Launched on August 19, the HVTN’s newly designed members’ site (https://members.hvtn.org) is now available to the Network. The main reason for updating the site was compliance driven. Since the old HTML-based site was not up to current standards for user and site security, moving the site to a new platform (SharePoint) was an efficient way to bring it up to date, while making it easier for HVTN staff to update content on their own. Moreover, SharePoint affords other advantages, such as more efficient workflow and document versioning, making the decision to move to this platform easier. Since the existing site was approximately 10 years old, other considerations for the site’s redesign included: Read more…
Earlier this year, data for 2 HVTN efficacy studies — HVTN 503 (final efficacy analysis) and HVTN 505 (results from an interim data safety and monitoring board [DSMB] unblinded review) –were released. Both analyses were planned – the HVTN 503 final efficacy analysis occurred at the end of 3.5 years of followup of the participants. The HVTN 505 interim unblinded analysis of efficacy was triggered, as specified in the protocol, “when the 30th Week 28+ infected individual had 20 weeks of follow-up post-diagnosis.” Both analyses offer important lessons and raise interesting questions in the challenging HIV vaccine trials field. Read more…