TMF Regulatory Requirements

Because of The Avoca Group’s extensive experience consulting for inspections/audits and the Avoca Quality Consortium® (AQC) Member companies’ input regarding their experiences with inspections/audits, The Avoca Group is able to provide unprecedented insight into the expectations of regulatory agencies. Based on these experiences and case studies, we’ve determined that inspectors often check that the TMF is complete, can be accessed directly, has audit trails to ensure record/data integrity, and contains original/certified copies of the documents.

Before addressing some of the questions for each of these inspection points that were asked during the webinar, it’s worthwhile revisiting some of the key principles from regulatory agencies.

EMA’s Good Clinical Practice Inspectors Working Group (GCP IWG) DRAFT Guideline on GCP compliance states “A TMF is the collection of essential documents that facilitates the conduct and management of the clinical trial and allows that the integrity of the trial data and the compliance of the trial with GCP can be evaluated.” According to Article 57 of the regulation, the essential documents are “those pertaining to the trial which allow verification of the conduct of the trial and the quality of the data generated.” Therefore, documents that are generated from following the systems and procedures that assure the quality of every aspect of the trial are considered essential documents.¹

The FDA’s Draft Guidance to Industry Data Integrity Compliance with cGMP states that “data integrity refers to the completeness, consistency, and accuracy of data. Complete, consistent, and accurate data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate (ALCOA).”²

According to the WHO’s Guidance on Good Data and Record Management Practices, “The audit trail is a form of metadata that contains information associated with actions that relate to the creation, modification or deletion of GXP records … creation, additions, deletions or alterations of information in a record, either paper or electronic, without obscuring or overwriting the original record. An audit trail facilitates the reconstruction of the history of such events relating to the record regardless of its medium, including the “who, what, when and why” of the action.”³

Therefore, the inspections around the TMF stem from the need to ensure that good practice is being followed to ensure the integrity of the data from which decisions regarding new drugs/devices are being made.

Completeness – Hybrid TMFs

According to the regulatory agencies, the TMF needs to provide all essential documents relevant to the clinical trial.

When the eTMF is a hybrid model (paper/electronic), the MHRA and EMA specifically have a strong preference to directly access eTMFs for inspection purposes. If a sponsor TMF is paper and the CRO TMF is electronic, then the sponsor is accountable for the entirety of all documents that support the conduct of the clinical trial, patient safety, and data integrity. The sponsor’s quality management system (QMS) should clearly articulate how the paper-based TMF and eTMF operate together to complete the TMF. Additionally, the contract or other document or procedure agreed between all parties should outline the arrangements for the TMF (which should include how the TMF would be made available if either party were to be inspected).

The TMF should include emails that contain relevant and important information about the clinical trial conduct; decisions that affect patient safety, data integrity, or key risks for the trial; and any documentation of actions taken for these items. However, having said this, best practice is not to document these items within emails, but rather to document them in actual team or study documents such as meeting minutes, trip reports, monitoring reports, or analysis reports.

One attendee reported experience with two MHRA inspections with different companies, during which the MHRA had a focus on data flows, data integrity, and awareness of the MHRA data integrity guidance. In our experience, although data flows are highly recommended, they vary widely among sponsors, studies, etc. It is important that the diagram include all data from the source (including sites, external vendors) to the generation of the tables/listings and any other format that goes into the CSR.

Accessibility

The MHRA and EMA expect that the eTMF will be straightforward in terms of use – not requiring extensive training for the inspector. They request direct access to it with minimal orientation.

Regarding access to data records, guided access is acceptable for certain data records within an esystem in addition to direct access to the TMF system. For example, we were asked during the webinar specifically about safety data – it is acceptable to reference in your TMF index the location of source safety data and direct an inspector to the Safety Database as the central repository for safety data. Other examples include audit trails and eCRF and CTMS. This is due to the technical nature of some of these systems, which might contain data rather than documents.

Audit Trails for Record/Data Integrity

How inspectors want to view the TMF’s audit trail differs by regulatory agency – whether it be the system’s back-end or an export of the audit trail. Certainly, the MHRA is known to request access to the TMF metadata, including the audit trail. If/where there is a particular reason why access to system back-end is not available, provision of exported audit trail can be negotiated, provided it is reliable (i.e., from a validated system).

The Avoca Group has many industry-leading oversight tools, and audits have been performed of these tools in practice, which have been found acceptable. A case study was presented by Alexion during the 2015 Avoca Quality Consortium Fall Members’ meeting regarding an agency inspection of their pharmacovigilance QMS. They had used Avoca leading practices. Upon completion of the inspection, the inspector indicated that it was the most effective management system he had seen. This case study is available to all AQC Members in the AQC online Knowledge Center. Other examples are available upon request.

Original/Certified Copies of Documents

Finally, we received multiple questions about document certification. Per EMA/15975/2016 definition (aligned with ICH), a certified copy is a paper or electronic copy of the original record that has been manually verified (e.g., by a dated signature) or has been generated through a validated process to produce a copy with the exact content and meaning of the original.

The best practice for certifying a document in an eTMF is to have a well-defined process in place that includes qualified individuals who are assigned to generate a copy, verifying (certifying) that it is identical to the original and signing for accuracy or have a procedure that documents the validated electronic process for generating the copy. There must also be internal organizational audit verification that copies are consistent with originals.

Regarding which TMF content requires a certified copy, the general principle is that original documents that are required for the TMF (e.g., ICH essential documents and/or other documents that are pertinent to the study) need to be transferred to an electronic format for eTMF filing. The transfer process should be validated and undergo regular quality control checks to ensure that the information will not be lost or altered. Whether the original hard-copy documents are kept by the CRO once they are uploaded into the eTMF depends on the risk level acceptable to the CRO and sponsor. In concept, once a document has been certified via a validated and documented approach, paper copies may be destroyed. Section 5.2 “Destruction of original paper after digitization” of the Draft EMA Guideline outlines several relevant points for consideration when making this risk-based decision.²

In the common scenario where the site process is to retain original (wet ink-signed) essential docs and they do not have a process to send in certified copies for filing in the eTMF, sites either send copies to the monitoring organization, post a scanned copy of the original in the eTMF, or have them collected by site monitors for filing in the TMF/eTMF. Since the site will have the original documents in the Investigator Site File that are verified by the site monitor, it is not typically expected that a certified copy process is implemented [since the original record remains available in the ISF (TMF)].

View and download the Webinar on which this blog is based. >>

Because this post was guided by the questions asked during our webinar, it touches only on a segment of all the considerations for the TMF. For additional information about any of these topics, the guidance documents issued by the regulatory agencies^1-4 provide their expectations for the majority of scenarios. Of course, we at The Avoca Group are available to provide our perspectives based on our experience and those of the AQC Member companies. For more information about our Consulting services, click here.

1. EMA: EMA/15975/2016, Good Clinical Practice Inspectors Working Group (GCP IWG), DRAFT Guideline on GCP compliance in relation to trial master file (paper and/or electronic) for content, management, archiving, audit and inspection of clinical trials, March 31, 2017: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2017/04/WC500225871.pdf
2. FDA: DRAFT Guidance for Industry Data Integrity Compliance with cGMP, April 2016: https://www.fda.gov/downloads/drugs/guidances/ucm495891.pdf
3. WHO: Guidance on Good data and Record Management Practices, Annex 5, September 2015: http://apps.who.int/medicinedocs/documents/s22402en/s22402en.pdf
4. MHRA: GxP Data Integrity Guide, March 2018: https://www.gov.uk/government/publications/guidance-on-gxp-data-integrity

The post Inspection Preparation With a Risk-Based Approach Consistent with ICH E6 (R2) Requirements appeared first on Avoca, a WCG company.

Is your company prepared?

The story begins with the simple question, “Is your company prepared to address changes to oversight resulting from ICH E6 (R2)?”

Almost three-quarters of providers (74%) agree or strongly agree that their company is prepared for these changes. That is understandable, since contract research organizations (CROs) have always had the responsibility to oversee any subcontractors they bring on. Plus, it should be noted that three-quarters of the provider survey respondents were CROs.

Sponsors, however, are not as confident, with only 58% indicating agreement/strong agreement. Sponsors are likely feeling pressure as they are now faced not only with overseeing the CRO they hire, but also any subcontractors the CRO utilizes.

There is a definite risk associated with having ultimate responsibility for a process while being one or two steps removed from it, if sufficient quality oversight is not present.

How are oversight practices working out?

Oversight practices can be a point of contention between sponsors and providers. Avoca asked sponsors to assess themselves in the areas of documentation and roles, and then asked providers to assess sponsors in the same areas.

As the chart below shows, the majority of sponsors feel fairly positive about their approach to documentation and roles/responsibilities. Most providers, however, don’t think sponsors are doing a great job.

What is the basis of this discrepancy in perspective? First, consider documentation. Providers rely upon documentation to do their job and fulfill sponsor expectations; they have a vested interest in that documentation being detailed and precise. Sponsors, on the other hand, may view documentation from a “defensive” position. That is, sponsors may prefer a high-level approach to documentation that allows greater interpretive freedom. This approach gives sponsors greater confidence in their ability to demonstrate compliance, but it can be at the expense of the specificity providers’ desire.

The next point of discrepancy involves defining roles to minimize duplication of effort. As with documentation, there appear to be divergent views between sponsors and providers. The third question shown in the chart, which asks about efficient use of resources, points to a likely reason for this discrepancy: namely, relatively low levels of agreement from both sponsor and provider perspectives with respect to the efficient use of resources suggests that, even if roles are clearly defined, work is still being duplicated on the job. Because sponsors have been given oversight responsibility, they may feel it incumbent upon them to duplicate work to verify outcomes. Providers, of course, view this as unnecessary and indicative of a lack of trust on the part of the sponsor.

How is risk-based provider oversight working out?

All that being said, what do sponsors and providers think about the impact of using risk-based provider oversight in terms of increasing quality, timeliness, and resource efficiency? The answer from both parties: not much.

How do we make this work – together?

For sponsors and providers to realize sustainable changes oversight practices as allowed by ICH E6 (R2), risk-based approaches must deliver quantitative benefits for quality, timeliness, and resource efficiency – far more so than it is currently doing. The data shown above from the 2017 Avoca Industry Report highlights three areas where sponsors and providers can improve to gain those benefits:

• Providers can share best practices with sponsors to help sponsors become more comfortable with their new oversight role.
• Sponsors and providers must define expectations for documentation and come to mutual agreement regarding its purpose, scope, and level of detail.
• Sponsors must establish a level of trust with providers to eliminate duplication of effort.

Risk-based provider oversight is an area of tremendous opportunity for sponsor and provider alike. To gain the value that it promises, however, sponsors and providers will need to work in closer collaboration and partnership than ever before.

Download Avoca’s 2017 Provider Oversight Industry Report.

Author:

Dennis Salotti Vice President, Operations, The Avoca Group

The post TEST RELATED Sponsor and Provider… appeared first on Avoca, a WCG company.

In Avoca’s survey, sponsors and providers were asked how familiar they were with risk-based approaches to inspection preparedness. But – this is key – responses were categorized based on whether the respondent was a member of the Quality department or was in Clinical Operations. Across sponsors and providers, Quality personnel indicated a significantly higher level of knowledge about risk-based inspection preparedness relative to those in Clinical Operations.

In other words, Quality is feeling really good about the new approaches to inspection preparation, but Clinical Operations is less confident and fluent. There are several contributing factors to this remarkable gap in self-assessed familiarity.

First, there is departmental friction: an ugly truth, but one that must be faced. Historically, Quality and Clinical Operations have not always had the best working relationship. Clinical Operations has often perceived Quality as a “policing” organization – the equivalent of someone coming in after you have cleaned the house from top to bottom and saying, “You missed a spot.” The result? Clinical Operations may not be particularly inclined to proactively collaborate with Quality, so may not be receiving the full benefit of Quality’s knowledge about risk-based inspection procedures.

Second, the two departments may have contrasting perspectives on who is responsible for the success of an inspection. Clinical Operations may view managing inspections as “Quality’s job.” However, while Quality is responsible for preparing for and hosting the inspection, the work under review has all been done by Clinical Operations. Both departments, therefore, are jointly responsible for a successful inspection.

Third, there may be an unconscious bias on the part of Clinical Operations that they don’t need to know best practices about risk-based approaches to inspection preparedness because Quality will tell them what they need to do when an inspection is foreseen. This sets the organization up for increased risk, because Clinical Operations may not proactively maintain a constant state of inspection readiness throughout the clinical trial’s process.

The gap in inspection preparedness can be closed – bringing both Quality and Clinical Operations up into the 90% range and higher – once both departments acknowledge that maintaining a constant state of inspection preparedness is everyone’s job. But to do this job, these departments need to partner together much more closely than ever before. Quality needs to systematically and conscientiously share its knowledge of best practices and inspection procedures with Clinical Operations. Clinical Operations should confer with Quality on a regular basis to optimize processes in line with ICH E6 (R2).

Success will be readily evident. When Quality and Clinical Operations partner together effectively, Clinical Operations as well as Quality will express confidence toward inspection preparedness – and the inspection itself will be passed with flying colors.

Is your organization inspection ready? The Avoca Group specializes in supporting sponsors and CROs to comply with ICH E6 (R2) through the use of risk-based approaches to quality and oversight. The Avoca Group’s consulting services are grounded in the leading practices and tools from the Avoca Quality Consortium® and customized to drive measurable improvements to quality and execution of clinical trials. To learn more, or to speak with a representative, contact us.

Download The 2017 Avoca Industry Report: Using Risk-Based Approaches to Inspection Preparedness

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Author:

Dennis Salotti Vice President, Operations, The Avoca Group

The post Is Your Organization Prepared for Risk-Based Inspections? Depends on Who You Ask. appeared first on Avoca, a WCG company.

The Avoca Group’s research, documented in the 2017 Avoca Industry Report, provides key insights into the complex dance between technology and risk.

Who is adopting technology for risk-based approaches?

To begin, there is a notable difference in technology adoption rates between sponsors and providers, with providers showing a higher adoption rate across the range of technologies evaluated (Figure 1). This is understandable, since providers are higher utilizers of technology in the course of their work. It is in their best interest to leverage any tool with the potential to speed up efficiency and improve decision making.

Figure 1

Exactly what is being adopted?

Figure 1 shows that, among Sponsors, there is a slightly higher utilization of less advanced technologies, such as statistical monitoring and data visualization, than there is of more advanced technologies, particularly decision analytics. This is important to note, as machine learning (ML) and other forms of artificial intelligence (AI) involved in decision analytics are what will identify patterns of potential risk over the course of multiple clinical trials and help Sponsors align with ICH E6 (R2) guidelines.

How is technology working out in managing risk?

The answer to this question is both good and bad. Approximately half of providers say the approaches are having a “very positive” impact (Figure 2). Sponsors were somewhat weaker in their response, which may be due to the fact that they are in earlier stages of adoption of the technologies (Figures 1 & 2). That being said, a significant proportion of both sponsors and providers do not see technology as having a “very positive” impact on managing risk.

Figure 2

Why isn’t there a greater positive impact?

The technologies that are available to support risk-based approaches to clinical trials are not yet mature. This is still a nascent technology environment with a great deal of room for improvement. Technology providers have a tremendous opportunity here to create or refine solutions to deliver a compelling user experience and outstanding return on investment.

Where is the “sweet spot” for technology in a risk-based environment today?

While, overall, technology has room for improvement to support risk-based management, there is a sweet spot that sponsors and providers can – and are – taking advantage of right now. That is in the area of site monitoring (Figure 3). Quality management is also being leveraged, to a slightly lesser degree.

Figure 3

Where could technology become transformative for risk-based management?

Looking at Figure 3, technology providers could transform clinical trial management by developing ways to improve provider oversight and inspection preparedness. These will be challenging, since the objectives and direct measures of success are arguably less discrete than for tasks such as site monitoring and quality management.

How happy are sponsors and providers with the technology they are using?

Both sponsors and providers are employing technology in risk-based approaches (Figure 1). But how happy are they about it? Here, we see a huge gap. Almost three-quarters of providers are satisfied with how technology is supporting risk-based approaches to clinical trial management, whereas only 36 percent of sponsors report a similar level of satisfaction (Figure 4). Considering the degree of perceived impact reported in Figure 2, it is understandable that sponsors have a low satisfaction level. Providers appear to be more generous with their assessment.

Figure 4

Where do we go from here?

Innovation demands change, and change is always uncomfortable. However, in the case of ICH E6 (R2), such change is demanded from both sponsors and providers. Technology is making headway into the risk-based environment, but technology providers have further work to do to prove the value of their tools and to help sponsors and providers become confident using the tools. The technology providers who do so will become key partners in transforming the risk-based landscape.

Are you struggling to determine how to identify, qualify, and select the right technology to support risk-based approaches at your company? The Avoca Group specializes in creating and improving ICH E6 (R2)-compliant Quality Management Systems and provides guidance in assessing, selecting, and implementing technology to support risk-based approaches to quality and oversight. The Avoca Group’s consulting services are grounded in the leading practices and tools from the Avoca Quality Consortium® and customized to drive measurable improvements to quality and execution of clinical trials. To learn more, or to speak with a representative, contact us.

Download The 2017 Avoca Industry Report: Using Technology in a Risk-Based Environment

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Author:

Dennis Salotti Vice President, Operations, The Avoca Group

The post Technology and Risk: How Systems and Software Are Impacting ICH E6 (R2) appeared first on Avoca, a WCG company.

Passive vs. Active

The Avoca Group’s research, documented in the 2017 Avoca Industry Report, shines a light on what’s happening with risk assessment and management across the board. First, the type of refinements sponsors and providers are willing to make tend to be more passive than active in nature.

Changes to the review plan for performance data or to the monitoring strategy are the most prevalent actions taken in response to risk assessments. In contrast, more aggressive actions, such as changes to trial operations – including changing the number or disposition of specific sites – are far less common.

Basically, sponsors and providers are willing to make “safe bets” – things that don’t have a huge impact on clinical trial operations or results. For example, a sponsor might increase the frequency of monitoring or the number of training sessions required. Such actions may or may not benefit the clinical trial, but they certainly won’t hurt it in any way.

However, when it comes to matters such as potentially changing the number of sites involved in a clinical trial – a decision that could seriously impact the logistics, cost, and outcomes of a trial – the willingness to take the plunge decreases substantially.

Severity vs. Detectability

A second point of consideration involves the components of risk assessment. ICH E6 (R2) lays out three areas of risk assessment: severity, probability, and detectability. Sponsors and providers are doing a good job assessing the severity or level of harm that a risk carries. Assessing the probability of a risk event lags behind that a bit but is still respectable. Nonetheless, the numbers definitely take a dive when looking at how often detectability is being assessed.

This brings up an important point: if sponsors and providers cannot see a looming risk, how can they address it? If sponsors and providers cannot detect where a risk lies, they are completely exposed to that risk.

Qualitative vs. Quantitative

Third, it should be noted that one of the goals of risk-based assessments is to give sponsors and providers hard facts to consider in decision-making processes. But, while approximately half of each group are using a hybrid approach of both qualitative and quantitative methods to assess risk, a significant minority still use a primarily qualitative approach to risk assessment.

This shows that there is work to be done for sponsors and providers overall to move to the place where they can say, “This is the data we used in our risk assessment. This is how we analyzed it. This is how we applied our expert judgment to that analysis in making our decision.” That mix of qualitative and quantitative approaches is where the highest level of benefit will be realized.

What’s the Impact?

One of the biggest red flags raised by the 2017 Avoca Industry Report is that both sponsors and providers view the new risk assessment and management approaches as having only a moderate impact on increasing quality.

Considering that the whole focus of ICH E6 (R2) is to improve quality in clinical trials, this is not good. It would be easy to blame the lack of impact on the nature of the ICH E6 (R2) guidelines. But the previous points beg the question: Might this lack of impact be attributable to…

• A tendency to prefer passive refinements to active ones.
• An uncertainty about how to assess detectability, as compared to severity, of risks.
• The exclusive use of qualitative methods for assessing risk, rather than a hybrid qualitative/quantitative approach.

In other words, are we not seeing a bigger impact because we have not been willing to make bigger bets? As long as sponsors and providers “play it safe,” it is reasonable to anticipate only mediocre results. What impact would ICH E6 (R2) have if sponsors and providers made aggressive refinements to their clinical trials based on their risk assessments? What would happen if risks could be detected with a high degree of precision? What if assessments were based on the perfect blend of the subjective and the objective?

I suspect that the impact which would result would, once and for all, answer in the affirmative the ultimate question: “Is this sustainable?”

Is your company moving toward greater use of risk-based approaches for quality and oversight? The Avoca Group specializes in supporting sponsors and CROs to comply with ICH E6 (R2) through the use of risk-based approaches to quality and oversight. The Avoca Group’s consulting services are grounded in the leading practices and tools from the Avoca Quality Consortium® and customized to drive measurable improvements to quality and execution of clinical trials. To learn more, or to speak with a representative, contact us.

Download Avoca’s 2017 Industry Survey Report

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Author:

Dennis Salotti Vice President, Operations, The Avoca Group

The post Are Risk-based Approaches to Assessing and Managing Clinical Trials Sustainable? appeared first on Avoca, a WCG company.

To begin, it is important to establish how familiar sponsors and providers are with risk-based approaches to quality management. Avoca’s research reveals that nearly 70% of sponsor respondents indicate having a “good” or “very good” understanding of best practices in risk-based quality management. While this is encouraging, it is significantly lower than the nearly 90% of providers who indicate this level of knowledge.

Breaking this down further, among providers, understanding of risk-based quality management was consistent by function across Quality and Clinical Operations. However, among sponsors, those in Clinical Operations expressed a substantially lower level of familiarity than did those representing the Quality function.

We can view this gap as an opportunity for Quality and Clinical Operations to increase collaboration and knowledge sharing. It may also indicate the need for a mindset shift in sponsor organizations from viewing quality management as “Quality’s job” to seeing it as “everyone’s responsibility.”

Familiarity with risk-based quality management protocols will also undoubtedly improve as the frequency of use increases. Currently, approximately 50% – 60% of sponsors and providers reported that risk-based quality management is being utilized in at least half of the trials they run. That is a positive sign but leaves significant room for growth.

Utilization is one thing – results are another. The Avoca report notes that approximately half of respondents indicate that risk-based quality management has been “very” or “extremely” impactful on increasing quality in trials; far fewer, however, feel this is resulting in improvements to efficiency in terms of time or resources.

When we put all these statistics together, what do we see with regard to risk-based quality management?

• Familiarity is good overall … but it could improve.
• Utilization is reasonably good … but it could improve.
• Impact is trending in a good direction … but it could improve.

This assessment might leave you feeling ambivalent about the long-term effectiveness and sustainability of risk-based quality management. But numbers aren’t the only considerations. The 2017 Avoca Industry Report also gathered verbatim commentary from respondents on the use of risk-based quality management. That commentary suggests that the use of risk-based quality management can positively influence awareness, communication, and strategy within and between sponsor and provider organizations. For example, respondents noted:

• “Planning has opened communication amongst team.”
• “Increased awareness of threats to quality of study.”
• “Our teams are constantly meeting and reassessing to make sure that the potential risks and actual risks are being pointed out and dealt with.”

Certainly, challenges were also reported, such as gaining alignment on rationale, process, and measurement. But even these challenges have their positive aspect if they drive greater collaboration between Quality and Clinical Operations, and among sponsors and providers.

Taken all in all, if risk-based quality management is bringing people together in new ways, that can only be viewed as valuable to the future of clinical trials and to the patients who are ultimately being served.

Are you concerned about compliance and effectiveness of your QMS or risk-based oversight practices? Avoca can help. We specialize in installing or remodeling Quality Management Frameworks that comply with ICH E6 (R2) and utilize risk-based approaches to quality and oversight. Avoca’s consulting services are grounded in the leading practices and tools from the Avoca Quality Consortium® and customized to drive measurable improvements to quality and execution of clinical trials. To receive information or to speak with a representative, contact us.

Download The 2017 Avoca Industry Report: Using Risk-Based Approaches to Quality Management

.

Author:

Dennis Salotti Vice President, Operations, The Avoca Group

The post Risk-Based Quality Management: Working It Out in the Trenches appeared first on Avoca, a WCG company.

Written and submitted by AQC Member, Craig Morgan, Head of Marketing, goBalto

If you fail to plan, you are planning to fail. These words ring true when it comes to study startup, a notorious bottleneck in clinical trials. With research showing a continually stagnating timeframe for conducting clinical trials and a trend toward improving study performance, quality improvement is moving to center stage. With the availability of workflow-based study startup tools (Figure 1), proactive planning, process optimization and quality improvements with study startup—as measured by inspection-readiness and the likelihood of passing regulatory audits—are within reach.

Proactive planning requires sponsors and contract research organizations (CROs) to identify the risks up front, as well as the study requirements, prior to study activation. Failure to do so results in problems not being identified until much later, often in advance of an inspection and well after completed documents, artifacts and metadata have already been released to the trial master file (TMF). A better strategy is to employ processes that take an upfront approach to preventing or mitigating problems associated with study startup document completion.

Fig 1: A country-specific workflow

Using a workflow-based approach to study startup, critical indicators of quality can be assessed on an ongoing basis so that corrective actions can be made earlier (e.g., inaccurate study indexing, missing documents (e.g., missing medical license if you have CV for an investigator), missing document completion date, etc.) This approach can break down silos that have long performed in isolation with little understanding of what the next department needs to fulfill its regulatory obligations and achieve targets measured by performance metrics. Overall, the study improves by greater adherence to timelines, and ultimately by the percentage of artifacts flowing into the TMF that meet quality standards (site activation generates an estimated 40% of all TMF artifacts.)

As the industry turns its attention to better planning, regulatory bodies are drafting regulations to ensure study quality, most notably ICH E6 (R2), which states that the sponsor should implement a system to manage quality throughout all stages of the trial process, including the beginning.

Through workflows, it is possible to launch the planning process by structuring artifacts specific to study activation, while facilitating the exchange of data among eClinical systems. With this capability, any and all needed documents can be defined. Importantly, artifacts and documents can be created 17 weeks before site activation, making it possible to ensure the downstream quality and facilitate inspection readiness at the site level. Making this process change can yield significant improvements to study execution.

Specifically, the regulatory quality assurance process [to ensure inspection readiness] should occur no later than four weeks after site activation, according to the Metrics Champion Consortium quality and methodology definitions*. With the use of upfront workflows, which provide stakeholders with insight months earlier quality can be moved 21-weeks upstream in the process.

Such initiatives to improve quality in early stages of transformational process changes can finally begin to happen as the availability of solutions become available. Research suggests that organizational issues become strategic and of interest to upper management once they have proven relevance to performance.

Learn more about leading practices for proactive study startup planning. View the recording and slides from a webinar, co-presented by The Avoca Group and goBalto on Thursday, May 3, 2018. Topics include how to effectively deliver on improved overall study quality while supporting regulatory compliance for provider oversight. Access the recording and slides here >>

*MCC TMF Implementation Scenario, Page 9.

The post Proactive Planning is Key to Process and Quality Improvements in Clinical Trials appeared first on Avoca, a WCG company.

Is your company prepared?

The story begins with the simple question, “Is your company prepared to address changes to oversight resulting from ICH E6 (R2)?”

Almost three-quarters of providers (74%) agree or strongly agree that their company is prepared for these changes. That is understandable, since contract research organizations (CROs) have always had the responsibility to oversee any subcontractors they bring on. Plus, it should be noted that three-quarters of the provider survey respondents were CROs.

Sponsors, however, are not as confident, with only 58% indicating agreement/strong agreement. Sponsors are likely feeling pressure as they are now faced not only with overseeing the CRO they hire, but also any subcontractors the CRO utilizes.

There is a definite risk associated with having ultimate responsibility for a process while being one or two steps removed from it, if sufficient quality oversight is not present.

How are oversight practices working out?

Oversight practices can be a point of contention between sponsors and providers. Avoca asked sponsors to assess themselves in the areas of documentation and roles, and then asked providers to assess sponsors in the same areas.

As the chart below shows, the majority of sponsors feel fairly positive about their approach to documentation and roles/responsibilities. Most providers, however, don’t think sponsors are doing a great job.

What is the basis of this discrepancy in perspective? First, consider documentation. Providers rely upon documentation to do their job and fulfill sponsor expectations; they have a vested interest in that documentation being detailed and precise. Sponsors, on the other hand, may view documentation from a “defensive” position. That is, sponsors may prefer a high-level approach to documentation that allows greater interpretive freedom. This approach gives sponsors greater confidence in their ability to demonstrate compliance, but it can be at the expense of the specificity providers’ desire.

The next point of discrepancy involves defining roles to minimize duplication of effort. As with documentation, there appear to be divergent views between sponsors and providers. The third question shown in the chart, which asks about efficient use of resources, points to a likely reason for this discrepancy: namely, relatively low levels of agreement from both sponsor and provider perspectives with respect to the efficient use of resources suggests that, even if roles are clearly defined, work is still being duplicated on the job. Because sponsors have been given oversight responsibility, they may feel it incumbent upon them to duplicate work to verify outcomes. Providers, of course, view this as unnecessary and indicative of a lack of trust on the part of the sponsor.

How is risk-based provider oversight working out?

All that being said, what do sponsors and providers think about the impact of using risk-based provider oversight in terms of increasing quality, timeliness, and resource efficiency? The answer from both parties: not much.

How do we make this work – together?

For sponsors and providers to realize sustainable changes oversight practices as allowed by ICH E6 (R2), risk-based approaches must deliver quantitative benefits for quality, timeliness, and resource efficiency – far more so than it is currently doing. The data shown above from the 2017 Avoca Industry Report highlights three areas where sponsors and providers can improve to gain those benefits:

• Providers can share best practices with sponsors to help sponsors become more comfortable with their new oversight role.
• Sponsors and providers must define expectations for documentation and come to mutual agreement regarding its purpose, scope, and level of detail.
• Sponsors must establish a level of trust with providers to eliminate duplication of effort.

Risk-based provider oversight is an area of tremendous opportunity for sponsor and provider alike. To gain the value that it promises, however, sponsors and providers will need to work in closer collaboration and partnership than ever before.

Download Avoca’s 2017 Provider Oversight Industry Report.

Author:

Dennis Salotti Vice President, Operations, The Avoca Group

The post TEST Sponsor and Provider: Two Very Different Perspectives on Risk-based Provider Oversight appeared first on Avoca, a WCG company.

Is your company prepared?

The story begins with the simple question, “Is your company prepared to address changes to oversight resulting from ICH E6 (R2)?”

Almost three-quarters of providers (74%) agree or strongly agree that their company is prepared for these changes. That is understandable, since contract research organizations (CROs) have always had the responsibility to oversee any subcontractors they bring on. Plus, it should be noted that three-quarters of the provider survey respondents were CROs.

Sponsors, however, are not as confident, with only 58% indicating agreement/strong agreement. Sponsors are likely feeling pressure as they are now faced not only with overseeing the CRO they hire, but also any subcontractors the CRO utilizes.

There is a definite risk associated with having ultimate responsibility for a process while being one or two steps removed from it, if sufficient quality oversight is not present.

How are oversight practices working out?

Oversight practices can be a point of contention between sponsors and providers. Avoca asked sponsors to assess themselves in the areas of documentation and roles, and then asked providers to assess sponsors in the same areas.

As the chart below shows, the majority of sponsors feel fairly positive about their approach to documentation and roles/responsibilities. Most providers, however, don’t think sponsors are doing a great job.

What is the basis of this discrepancy in perspective? First, consider documentation. Providers rely upon documentation to do their job and fulfill sponsor expectations; they have a vested interest in that documentation being detailed and precise. Sponsors, on the other hand, may view documentation from a “defensive” position. That is, sponsors may prefer a high-level approach to documentation that allows greater interpretive freedom. This approach gives sponsors greater confidence in their ability to demonstrate compliance, but it can be at the expense of the specificity providers’ desire.

The next point of discrepancy involves defining roles to minimize duplication of effort. As with documentation, there appear to be divergent views between sponsors and providers. The third question shown in the chart, which asks about efficient use of resources, points to a likely reason for this discrepancy: namely, relatively low levels of agreement from both sponsor and provider perspectives with respect to the efficient use of resources suggests that, even if roles are clearly defined, work is still being duplicated on the job. Because sponsors have been given oversight responsibility, they may feel it incumbent upon them to duplicate work to verify outcomes. Providers, of course, view this as unnecessary and indicative of a lack of trust on the part of the sponsor.

How is risk-based provider oversight working out?

All that being said, what do sponsors and providers think about the impact of using risk-based provider oversight in terms of increasing quality, timeliness, and resource efficiency? The answer from both parties: not much.

How do we make this work – together?

For sponsors and providers to realize sustainable changes oversight practices as allowed by ICH E6 (R2), risk-based approaches must deliver quantitative benefits for quality, timeliness, and resource efficiency – far more so than it is currently doing. The data shown above from the 2017 Avoca Industry Report highlights three areas where sponsors and providers can improve to gain those benefits:

• Providers can share best practices with sponsors to help sponsors become more comfortable with their new oversight role.
• Sponsors and providers must define expectations for documentation and come to mutual agreement regarding its purpose, scope, and level of detail.
• Sponsors must establish a level of trust with providers to eliminate duplication of effort.

Risk-based provider oversight is an area of tremendous opportunity for sponsor and provider alike. To gain the value that it promises, however, sponsors and providers will need to work in closer collaboration and partnership than ever before.

Avoca offers consulting support to design or improve industry-leading systems for vendor quality oversight and compliance with ICH E6 (R2). Unique to Avoca, our consultants customize and implement industry leading tools and practices for Provider Oversight developed by the Avoca Quality Consortium®. To receive information or to speak with a representative, contact us.

Download The 2017 Avoca Industry Report: Using Risk-Based Approaches to Provider Oversight

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Author:

Dennis Salotti Vice President, Operations, The Avoca Group

The post Sponsor and Provider: Two Very Different Perspectives on Risk-based Provider Oversight appeared first on Avoca, a WCG company.

The striking change is the spirit in which the new set of guidelines is encouraging a shift in mind set in managing quality in clinical trials. ICH E6 (R2) is calling upon legions of drug development professionals to recognize that all risks are not of equal importance from a compliance and quality perspective and the key to effectively achieving quality is through making key decisions based on a careful assessment of risk.

Risk, a term that usually tends to invoke shudders because it is all about the “possibility that something can go wrong” is now omnipresent in quality management.  Risk based approaches to oversight, monitoring, inspections and more are the new normal.

There is a lot of frenzy around understanding the guidelines.  There are a lot of processes being put in place to make sure that ICH E6 (R2) is kept at the forefront of the way clinical trial processes evolve.  My question is this.  How are organizations getting their teams to change their mindset?  As far as I can remember, the words quality and compliance were at the heart of decisions.  How does one get employees to talk about and manage risk?

Since the launch of our Avoca Quality Consortium (AQC) five years ago, we have been working with our Members to prepare for this changing environment through the raising of awareness, cross-industry dialogue and the development of proactive, tool based approaches to managing quality.  Our Members believe that the best way to approach this change is to get the conversations flowing, not just within companies, but across the clinical trial ecosystem.

At our recent AQC Member meeting with executives, we heard loud and clear that the industry is mobilizing resources to understand and respond to the new guidelines.  This is now on top of our initiatives for 2017 where we will help our Member companies to understand the implications of ICH E6 (R2), guide them with leading practices and develop tools to respond and stay ahead.

We’d love to hear your thoughts on where you are in your journey in this risk based world of quality management.

Until next time………

Lakshmi

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Lakshmi Sundar has spent two decades in the pharmaceutical industry, leading teams across sponsors and CROs in multiple functional areas to spark innovation, manage risk, and lead change with a sense of purpose and fun. At Avoca, Lakshmi partners with members of the Avoca Quality Consortium and industry innovators to deepen the dialogue on building a quality culture within and across organizations to mitigate risk, advance drug development, and bring treatments to patients in a more effective manner. 

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