Quality by Design: Risk-Based Approach to Clinical Trials

Internet gamblingLast week, ARITHMOS attended the GIQAR conference in Italy which focused on managing changes to GxP guidelines. ARITHMOS’ Stefano Piccoli presented at the conference on the topic of Quality by Design and how to prevent failure in monitoring by anticipating and mitigating risk when it comes to technology solutions.

The overall problem is that current practices in clinical research are not proportionate to risk or well-adapted to achieving the desired goals. Some origins of this problem include:

  • The costs of clinical development
  • Globalization of clinical trials which complicates the regulatory and business environments
  • Risk Aversion
  • Poor study design and processes
  • Failing to identify the individual implementation needs of quality control activities

The goal of Quality by Design is to build in quality prospectively rather than “test it in” retrospectively. This means identifying in advance the risks to quality and planning how to avoid them.

In terms of Quality Risk Management, the FDA is expecting a shift from data-heavy NDA/BLA submissions to “knowledge-rich” submissions with insight from QRM practices. Likewise, the EU expects risks to be identified prospectively and concepts to be applied at the early program design stage before individual trials are running.

How can Quality by Design help in clinical drug development?

  • Designing optimal infrastructure
  • Optimizing processes and systems
  • Mitigating risks associated with clinical programs and individual studies
  • “Fit-for-purpose” monitoring
  • “Fit-for-purpose” training and communication
  • Enhancing GCP compliance and reducing audit/inspection findings
  • Meeting health authority expectations
  • Reducing the likelihood of costly errors
  • Getting it right the first time and avoiding the need to “fix” it down the road

Risk Based Approach to CSV

Computerized systems that support GxP processes must be validated in proportion to the level of risk they present to patient safety, product quality and the integrity of regulated records. The validation effort should be concentrated on the areas with the most risk.

There are 5 steps to a Quality Risk Management process which is designed to scaled according to the level of risk, complexity and characteristics of individual systems.

  • Step 1: Perform Initial Risk Assessment and Determine System Impact
  • Step 2: Identify Functions with Impact on Patient Safety, Product Quality, and Data Integrity
  • Step 3: Perform Functional Risk Assessments and Identify Controls
  • Step 4: Implement and Verify Appropriate Controls
  • Step 5: Review Risks and Monitor Controls

ARITHMOS’ team of expert CSV and Life Sciences Application consultants, certified in COBIT 5 and ITIL, provide two approaches to Computer System Validation. The strategic approach involves appropriate expert planning, risk assessment, business process analysis and defining user requirements. In the maintenance approach, on-going project management and periodic compliance reviews ensure technologies are safe and accurate for end users through a continuously documented process. 

To schedule a pre-assessment meeting with one of our experts, contact us at info@arithmostech.com.



Guide to Selecting an EDC System: Cost vs Functionality Matrix

When it comes to selecting an EDC vendor, it seems that most vendors fall into one of two categories: advanced technology and competitive pricing or moderate to baseline technology at a low cost. While budget is a major concern for most Sponsors, how can they be sure they are choosing the right technology to produce the best study results? ARITHMOS has put together a cost vs functionality matrix followed by a list of considerations for selecting an EDC system for your next study.


Click to enlarge


1. Cloud-based Technology

An EDC solution provided in Software as a Service (SaaS) cloud computing mode can improve the drug/device development process in terms of greater efficiency, a better decision-making process and cost-cutting measures. Sponsors can resolve discrepancies faster and reduce time and costs with immediate feedback from patients. A cloud solution can organize multi-language, global study data into a single database, improving the quality of data through automated edit and discrepancy checks and faster data cleaning.

2. Support Level

What is your ideal level of support for an EDC system? The more advanced systems provide excellent initial training programs and top level support through HelpDesk and study guidance. The baseline technology systems allow the Sponsors to work more autonomously with regards to study build and management. However, in this case the user interface needs to be intuitive and easy to navigate.

3. Hosting and Licenses

Consider how you will manage the EDC license and hosting options. Some systems include this in an inclusive package and others will provide various “à la carte” options.

4. Integrated Platforms

Some EDC systems are part of a larger integrated platform for seamless data integration among ePRO, CTMS, IRT and other clinical research systems. Falling into the advanced technology, competitive pricing category, an integrated system may be worth the investment for your program of studies.

clinical-trial-deviceLastly, don’t forget your functionality checklist while evaluating EDC systems:

  • Can you build your own study?
  • Are there data entry, coding and randomization features?
  • Are there Project Management tools?
  • Are there customized reporting features?
  • Are there re-usable templates and forms?
  • Is the system compatible with GCP and/or regulatory guidelines? Is there an audit trail?
  • Can the system handle multicentre, global studies?

Enhancing Risk-Based Monitoring with Data Visualization & Analytics

In anticipation of German ePharma Day on the 26th of June which is focused on “Risk-Based Monitoring in Clinical Trials”, ARITHMOS is looking at how to implement data visualization and analytics tools and strategics to enhance risk-based monitoring.

StatisticsRBM combines on-site monitoring with centralized remote monitoring supported by the study biometrics team (e.g. Data Managers, Statisticians, etc.). The RBM strategy should be considered in the protocol design stage, and therefore Data Managers can include RBM in the Data Management Plan and Statisticians can plan accordingly for their analyses.

The key factors in RBM are:

  • Patient Safety
  • Data quality/integrity
  • Protocol adherence/deviations
  • Monitoring time/cost efficiency

Therefore, monitoring is not only the responsibility of the Monitor, it becomes a cross-functional activity shared among different functions who handle data. Successfully managing a Risk-Based Monitoring approach requires metrics and reports tailored according to risk indicators as well as reporting, analysis and visualization technology solutions.

Executing RBM

Centralized/off-site monitoring can be supported by data taken from:

  • EDC systems
  • CTMS
  • Safety databases
  • Study documentation

RBM diagram

In a typical scenario, data and reports are taken individually from various systems. It makes it difficult to analyze the data for critical key factors and protocol adherence and to then make timely decisions according to the risk mitigation plan.

A solution allows those involved in RBM to create the information they need, share that information and analyze it in order to make crucial decisions such as when to trigger a monitoring visit when data comes in above or below thresholds or highlighting non-performing sites at the earliest time.

Business Intelligence tools are the best technology option for Risk-Based Monitoring. They allow for data retrieval, report development from different data sources, report delivery and cloud-based technology. Web-based applications can be accessed from various devices including PC/laptops, smartphones and tablets. It is important to note that these tools are also visualization and analytics tools which have additional features to support RBM. Some distinct features for RBM include:

  • Birthdays and Initials: match subjects based on birthdates or initials to identify subjects that enroll in study more than once
  • Perfect Schedule Attendance: Perfect scheduling based on expected study visits may be too good to be true.
  • Duplicate Records: identifying a set of test values that are repeated within or across subjects can indicate a problem.

In cases of IMP studies, data are available from previous studies, and often times this data is not used. Business Intelligence tools can pull data from the data warehouse in order to complete risk assessments and define critical data and processes.

Data, reports and analysis are key factors in an efficient application or RBM. A Business Intelligence solution can support ongoing monitoring through ad-hoc reporting, analysis capabilities, visualization, real-time data availability and information sharing. These tools can also support new studies by accessing historical data, better identifying risk factors and thresholds and better designing study protocols.

If you are interested in technology solutions such as Electronic Data Capture and Data Visualization tools for your Risk-Based Monitoring strategy, please contact us at info@arithmostech.com.

A Strategic vs Maintenance Approach to Computer System Validation

keyboard-with-security-buttonAs mentioned in our last blog post on IT quality, the costs associated with poor quality outweigh the costs of investing in validated, quality systems. IT quality and validation deliver systems which are fit for their purpose and comply with pharmaceutical regulation requirements. This week, ARITHMOS outlines a strategic vs. maintenance approach to Computer System Validation best practices. 

First of all, Sponsors should know that computer system validation in the pharmaceutical industry is applied from discovery through to manufacturing and supply. The GxP standards – including Good Laboratory Practice (GLP), Good Clinical Practice (GCP), Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP) – are applicable throughout the drug life cycle, and Sponsors should be asking themselves:

  • Do we have documentary evidence to prove our systems work as expected?
  • Are our systems developed, used and supported in a controlled manner?
  • Are we in compliance with 21 CFR Part 11 and/or EU Annex 11 and do we know how they differ for our drug development in Europe vs. US?
  • Have we assessed our systems in accordance with GAMP 5?
  • Are our systems validated according to industry and international standards?

Sponsors can take a strategic or maintenance approach to Computer System Validation – or even a hybrid model of strategic implementation and and continuous follow up.

The strategic approach to CSV means appropriate and expert planning, risk assessment and defining user requirements to guarantee the best approach. This includes business analysis by an expert consultant to include a gap and risk assessment, validation and mitigation plans, strategic planning and initial training.

Once a computer system is validated, it is important to maintain the system’s IT quality to avoid malfunctioning systems and to keep up-to-date on changing regulatory requirements. Risks associated with not maintaining IT quality include:

  • New vulnerabilities will no longer be collected, reported or analyzed
  • High risk of cyber attack on data integrity and data confidentiality (especially is working on a cloud-based environment)
  • Potential violation of data security laws
  • Non-compliance with industry standards

A maintenance approach to CSV would ensure technologies are safe and accurate for end users through a documented process for ensuring the system continuously does what it is designed to do. In a maintenance approach, services would include on-going project management, periodic review, change control, internal audit support and continuous training.


ARITHMOS has a team of expert consultants who provide strategic advice on the right validation plan for your computerized system in the pharma industry. We also provide on-going project support for maintenance activities including offering a flexible pricing model: either on a case-by-case basis or a fixed fee monthly rate.

Contact ARITHMOS’ CSV experts for a pre-assessment meeting to see which approach works best for your company. Contact us at info@arithmostech.com.