Drug safety evidence aggregation platforms are becoming a vital tool for pharmacovigilance departments at pharmaceutical manufacturers.

Throughout this guide, specific use cases for will be provided for a drug safety data aggregation platform designed for all functions within a pharmacovigilance department, including signal detection, safety science, and epidemiology.

Chapters in this guide include:

What is a Drug Safety Evidence Aggregation Platform?

How is an Evidence Aggregation Platform Different from Traditional Signal Detection Software?

Case Study- Signal Detection Utilizing FAERS Data

Case Study- Analyzing the Safety Landscape of Oral vs. Injectable Drugs

Case Study - Establishing Drug Safety Benchmarks for a Clinical Stage Product

Why choose Advera Health’s Evidex™ as Your Drug Safety Evidence Aggregation Platform

Want the PDF version? Download it here.

Drug safety data to support the entire lifecycleAn evidence aggregation platform is a web based software-as-a-service (SaaS) application that takes disparate sources of data, or evidence, and combines those data together using analytics to create new insight.

A drug safety evidence aggregation platform can read adverse event data points from multiple clinical trial results and perform on-demand meta-analyses to better understand side effect rates for drugs. The platform can then compare side effect rates from clinical trial results to side effect rates found in real world data such as the FDA Adverse Event Reporting System (FAERS) database, an organization’s internal safety data, and/or multi-payer claims data.

This combination of data sources helps to support pharmacovigilance and safety science teams by providing clean, standardized, and linkable clinical and real world data on both approved and pipeline products. The insight gained from an evidence aggregation platform aides in signal detection, epidemiological research, and evidence generation and supports organization wide decisions.

The best drug safety evidence aggregation platforms provide unique datasets that a user would not be able to gather themselves, as well as offer the benefit of customization. An example would be one that presents vendor curated data, such as annotated data from curated clinical trial results, FDA Adverse Event Reporting System (FAERS) data, and then also incorporates internal safety data from a database such as ARGUS® or client licensed claims data.

chapter2.pngThe key difference between traditional signal detection software and a drug safety evidence aggregation platform comes down to the types of data they each support, the flexibility in which those data are supported, and the much broader use cases available through an evidence aggregation platform.

Drug safety data from various sources are needed throughout a drug’s lifecycle to support a wide range of regulatory requirements, clinical decisions and planning, as well as commercial positioning and evidence generation. These data can be categorized into three buckets: company owned, vendor curated, and licensed data.

Company owned data include those captured in a clinical safety database or the data that are received post-marketing from spontaneous reporting that are stored in databases such as ARGUS. Overlaying a front-end on these databases has been at the heart of traditional signal detection software. The process with legacy software providers is long and complicated, with a significant investment needed in terms of both budget and time. The largest organizations have the resources needed to make this investment, however the configuration is not flexible and the software itself is typically used by only a handful of experts. Smaller organizations who have a need for signaling on their own data are often forced to rely on 3rd party consultants to either administer the software or to run the necessary analytics on behalf of the organization.

By contrast, a drug safety evidence aggregation platform is agile and flexible, while still maintaining analytical rigor. If the platform has an easy to use front end, then users do not have to be “experts” or even technically trained. During implementation of the evidence aggregation platform, users are on-boarded using the curated data preloaded in the platform.

Vendor curated data includes FDA Adverse Event Reporting System (FAERS), WHO’s Vigibase, and the various, unstructured data that exist such as clinical study results that are published in government registries like clinicaltrials.gov or found in publications, abstracts, and poster presentations. FAERS data have long been included in traditional signal detection software, but it’s use has been limited to certain power users or dedicated informatics teams. An evidence aggregation platform makes these data and the related analytics easy and provides for a robust source of insight.

Curated study results data have long been restricted to time consuming literature reviews and manual collection processes. Safety science and epidemiology teams have historically mined these data by hand, but manually scaling and updating these data is nearly impossible.

Databases of study results now exist that can be pre-loaded into an evidence aggregation platform. Analytics included in the platform can provide for on-demand pooled meta-analyses at the AE level, and then mapped and matched back to both company owned and curated FAERS data.

Licensed data are those data assets that an organization licenses from different vendors. Examples of these data include multi-payer claims, social listening, search query logs, and provider transcripts. These sources vary widely in structure and use case and can often sit in different areas of the organization. For example, multi-payer claims data, while having a clear benefit for drug safety teams, are often held by outcomes groups, and the data are not easily accessed or shared outside of the group.

Evidence aggregation platforms can corral these licensed data into one interface by matching and standardizing outputs to map back to both company licensed and public data. This allows for investigation into the data across disparate data sources and 360° view into safety issues.

Drug safety evidence aggregation platforms are becoming a vital tool for pharmacovigilance departments at pharmaceutical manufacturers. Throughout the next chapters in this eBook, specific use cases for will be provided for a drug safety evidence aggregation platform designed for all functions within a drug safety department, including signal detection, safety science, and epidemiology.

Next gen technology allows non-technical users to build on disparate data sources and allows organizations to access what they need, when they need itOne of the key benefits of a drug safety evidence aggregation platform is the data source flexibility it provides. Historically, smaller organizations have put off automating aggregate signal detection to avoid the cost and time commitment needed to implement traditional signal detection software. And those organizations that do have traditional software installed, have typically limited use to specific functional areas within drug safety and “expert” users, making access to FAERS data and analytics hard to access.

However, with an easy-to-use evidence aggregation platform, smaller organizations no longer need to put off automating aggregate signal detection. The resources needed to get up and running are minimal, and the platform allows for easy scalability when the team is ready to increase its efforts. In larger organizations with established workflows, a drug safety physician would not have to request an analysis of FAERS data to use as a benchmark. Rather, she would be able to access the data herself on-demand.

A drug safety evidence aggregation platform is a great solution for these two scenarios as it can provide an easy-to-use interface to access both qualitative data such as labeling information, seriousness, and disease related classifications, as well as sophisticated data mining analytics such as reporting odds ratios (ROR), proportional reporting ratios (PRR), and other safety specific statistical calculations. The flexibility of the platform allows for on-demand add-ons of other datasets such as curated clinical study outcomes data, their own internal data from safety systems, or other real world data like claims and social listening.

scalable, flexible, and agile platofrm exists to bring together the data and analytics that you needOnce approved, an oral drug in development will compete with currently marketed injectable drugs. There was a need by the oral drug’s manufacturer to understand safety differences between currently marketed oral vs. injectable products to fully understand the potential safety concerns, identify points of differentiation between products, and pinpoint specific future evidence generation opportunities.

The evidence aggregation platform was used to identify products on market with the same active ingredient that had both oral and injectable delivery, and then to probe adverse event reporting differences between active ingredients that are administered both orally and by injection.

The platform was able to quickly show all of the spontaneously reported adverse events, as well as calculated disproportional reporting rates, and reporting rates, it was simple to select specific MedDRA preferred terms (PT) and broader Standardized MedDRA Query (SMQ) topics that were seen to show the largest differences between formulations of the same drug.

Thrombocytopenia and thrombocytopenia-related disorders were reported to FAERS disproportionately higher with injectable products on the market compared to oral formulations. Since the evidence aggregation platform being used for this example had embedded MedDRAà ICD-9/10 mapping, validation of the differences in these types of events could be seen using active surveillance with claims data.

The result of this data collection was deep understanding of how the oral product’s adverse event could be characterized. With this insight in hand, the manufacturer could more effectively develop strategy to take advantage of the safety differentiation.

A pipeline product has been put on clinical hold by FDA due to an unexpected serious adverse event in a trial. The trial’s sponsor needed to act fast to lessen the impact of the delay. Is this something that should be expected? Do competitor drugs have similar profiles? Will the adverse event impact market potential?

These types of questions can only be answered when various stakeholders come together to provide insight.  The first order of business is to ensure the proper data are available. The sponsor needs to establish a benchmark rate of adverse event occurrence across all drugs for the same indication in past clinical trials as well as in real world data. This is where a drug safety evidence aggregation platform is extremely beneficial.

First, a curated clinical study outcomes database allows the sponsor to quickly identify all trials, for all drugs in the indication that presented the same or similar adverse event. With an evidence aggregation platform, data reporting delays, non-standardization of results data, and other incongruities are corrected, providing for easy search and retrieval of data points.

Second, given that results data are captured as metadata from each trial, pooled rates for the adverse events for each drug were calculated to identify incidence rates drug-by-drug, rather than trial-by-trial. An evidence aggregation platform can then combine drug-by-drug rates to a combined pooled analysis to establish an indication-wide baseline adverse event rate, as seen in clinical trials.

Next, these clinical trial results data can be matched to spontaneous reporting in FAERS, combined with patient utilization numbers, to establish a real world adverse event reporting rate. Using customized analytics on claims data, also loaded into the evidence aggregation platform, allows for an additional “version of the truth,” giving the sponsor a 360⁰ view, and a true baseline rate for the adverse event. 

The result of the use of an evidence aggregation platform allows for the key questions to be answered quickly, helps to accelerate the lifting of the clinical hold, and provides a better understanding of how the adverse event impacts potential market share.

safety data standardization with Advera Health's RxFilterAdvera Health’s Evidex™ is a drug safety evidence aggregation platform that makes disparate drug safety data actionable though a simple to use yet powerful web-based application. Evidex provides proprietary curated data and analytics while allowing for custom data integrations.

Quick searches and an intuitive user interface empower use of Evidex at all organizational levels without the need for data scientists. The platform enables quick comparisons of drugs across data sources by indication, class, or mechanism of action, providing easy identification of differences in safety that previously could not be known.

 

Proprietary Data Assets included in Evidex™

Curated FDA Adverse Event Reporting System (FAERS)

Advera Health provides the gold standard for cleaned, standardized, and curated FAERS data, using proprietary RxFilter® technology. With roughly ten million case reports, covering roughly 2,300 FDA approved drugs, everything is covered including in-patient, out-patient, and specialty therapies.

All FAERS data in Evidex is fully mapped to clinical trial results data.

FAERS data in Evidex spans 690 indications and 389 mechanisms of action matched via VA-NDFRT and is segmented by age, gender, and condition. The database is searchable by every FAERS field available, including over 100,000 literature reference adverse events.

Data mining analytics are provided out-of-the-box for signal detection and proprietary safety signaling is included with the peer-reviewed and published RxSignal® analytic.

As with all datasets included in Evidex, MedDRA, ICD-9, RXNORM, and OHDSI CDM mappings allow for use with client provided drug databases and real world data such as claims.

Proven algorithm plus human intelligence for 100% clean and standardized FDA Adverse Event Reporting System (FAERS) database

Clinical Trial Safety Outcomes

Advera Health provides an annotated dataset from curated clinical trial results extracted from government registries such as Clinicaltrials.gov, published research, abstracts, and poster presentations. The distinct data fields are extracted into data tables including basic trial information, study arms, interventions, baseline characteristics, participant flow, reported adverse events, outcome measures.

Those data are matched and standardized using proprietary RxFilter® technology plus trained analyst work.  New data are updated within one week of being released. As with all datasets included in Evidex, MedDRA, ICD-9, RXNORM, and OHDSI CDM mappings allow for use with client provided drug databases and real world data such as claims.

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Custom Data Integrations

Evidex’s custom data integrations allows clients to BYOD… Bring Your Own Data.  With flexible back-end methodologies supporting any data set and experience with both standardized and unstructured data, the possibilities of what can be aggregated and linked are virtually endless.

With all FAERS-reported adverse events in MedDRA mapped to ICD-9/10, there is no need to predetermine what to look for. Ongoing, active AE detection across multiple datasets provide for a hypothesis-generating format that supports multiple functions within the organization.

Standardized, yet flexible design allows for customized, pre-defined cohort development for standardized tracking along with the flexibility to adjust observation protocol based on new data.

As with all datasets included in Evidex, client provided databases and other real world data are mapped to both clinical trial results and FAERS data assets through MedDRA, ICD-9, RXNORM, and OHDSI CDM mappings.chapter8.png

How Pharmacovigilance Departments can Work Smarter, Act Bigger

Most pharmacovigilance departments are resource constrained. Whether its human capital, budget, or both, the drug safety specialists within pharmaceutical companies are being asked to do a whole lot with very little.

 

What Happens When a Safety Signal Contradicts Clinical Trial Data?

Last month, FDA released their quarterly watch list of ongoing drug safety concerns. My colleague Jim wrote a blog post on some of the major talking points around the update, not on the drugs or the risks themselves, but general pharmacovigilance themes. Our post this week focuses on one of the risks that was specifically discussed by FDA on the SGLT-2 class of diabetes drugs.

 

Dear FDA, There is no Single Standard of Truth

Looking for a single truth standard is appealing in today’s lax regulatory environment.  It sets a defined minimally acceptable bar. Give us this, show us that, and then round go and collect $2 billion. This type of binary thinking worked for Dr. Gottlieb when he was creating an investment thesis at his hedge fund.  But in the real world its not just capital, but patient lives at stake. 

 

Drug Safety Progressives - The Rise of the Pharmacovigilante

If the Pharmacovigilantes’ voice becomes the majority, 2017 will be the year of drug safety, as my colleague Brian suggested in this blog, earlier in the year. And after attending the conference, I’ve identified three main themes surrounding the use of data and technology that Drug Safety Progressives are using to make Brian’s predictions a reality.  

 

Increasing Pressure for Increased Pharmacovigilance Capabiliteis

On top of the ever-increasing case processing, safety teams are now expected to do more to support the entire enterprise. They are being asked to contribute expertise and data to go/no-go decisions for pipeline drugs, help generate evidence to get a new drug accepted by payers and health authorities, and of course meet business and regulatory requirements for post-marketing safety commitments.

 

Pharmacovigilance and Drug Safety are Now More Important Than Ever

Dr. Scott Gottlieb, the recently confirmed new head of FDA, is pushing for more accelerated drug approvals.  And, in short, more accelerated approvals = more safety issues in the real world. 

 

What is a Drug Safety Data Aggregation Platform? 

Evidence aggregation platforms are becoming a vital source of intelligence for various healthcare decision makers in both pharmaceutical companies and managed care organizations.

 

How is Evidex Different from Traditional Drug Safety Platforms?

When first talking with drug safety departments, we often get asked how our platform is different than systems that they already have in place. 

 

Monitoring Biosimilars with a Drug Safety Data Aggregation Platform

A drug safety data aggregation platform is the perfect tool to create dashboards to monitor multiple sources of data on both reference drug and biosimilar products and begin to make comparisons. There are three key data sources that should be used.

 

Uncover Hidden Data Points with a Drug Safety Data Aggregation Platform

One form of hidden data points are adverse events that are not listed as “serious” in clinical trials because they do not lead to death, hospitalization, or life-threatening situations. An evidence aggregation platform that uses clinical trial results linked to real world data can identify these types of hidden events.

 

Establish Adverse Event Benchmarks with a Drug Safety Data Aggregation Platform

A drug safety data aggregation platform should allow the sponsor to quickly identify all trials, for all drugs in the indication that presented the same or similar adverse event. With an evidence aggregation platform, data reporting delays, non-standardization of results data, and other incongruities are corrected, providing for easy search and retrieval of data points.

 

A Drug Safety Data Point Nobody Knows About

In the Q3 2014 FDA Adverse Event Reporting System (FAERS) data file, FDA quietly added a new field that links a patient and case report to a literature reference. Or in other words, there is additional information on the adverse event (AE) report that previously was not available. 

 

Using FAERS data and Clinical Evidence to Compare HER2+ Antagonists

A walk through demonstration with screen shots showing how to obtain the data on Kadcyla within our Evidex platform.