Does the TransCelerate RbM Guidance Offer Standardization?

The concept of risk-based monitoring (RBM) is evolving, as nonprofit organizations continue to collaborate with the biopharmaceutical/medical device industry to investigate, pilot and implement RBM practices.  While the industry seems to be getting closer towards implementing RBM programs, the subject is still at its infancy, as the industry explores this paradigm. 

The biopharmaceutical/medical device industry is still trying to find ways to establish standardization in its business processes and technological infrastructures in order to seamlessly conduct RbM, however, current RbM practices lack standardization.  This, in essence, defeats the core purpose of RbM, which involves generating reproducible and consistent results in monitoring and study execution quality. 

In many industries, defining a process requires standardization in order to yield quality and reproducible results. Albeit clinical trials are far from a manufacturing process, clinical trial design is becoming a standardized and scalable operation.  For example, the FDA successfully executed the Master Lung Protocol, which achieved numerous study outcomes for several therapies.  Moreover, standardization is moving into different therapeutic areas, such as CNS.  “There are organizations that plan to conduct proof of concept and confirmatory Alzheimer’s studies by means of a shared protocol,” said Beat Widler, Partner at Widler & Schiemann Ltd.

In a biopharmaceutical/medical device environment that implements standardized operational and technological infrastructures, standardization is going to be an essential aspect of seamless clinical operations implementation.  This article will explore current practices and guidances on RBM, and then recommend other options for consideration.

TransCelerate Biopharma’s Position on RbM Standardization

TransCelerate is currently leading the way in evangelizing its RBM ideology.  TransCelereate has developed a process which advises study teams to evaluate risk from numerous and comprehensive standpoints.  While these tools can assist study teams with categorically interpreting risk factors during trial design, the process introduces a great level of subjectivity, which can impact RbM results from one trial to another.

To demonstrate, The Risk Assessment Categorization (RACT) Tool asks study teams to evaluate risk factors, such as the risk impact of compound interactions with other medications, and the severity of subject population conditions; subjective interpretation of these risks introduces inconsistency in standardizing risk assessments in clinical operations, which brings in variability during clinical trial risk assessment design and implementation.  Additionally, RACT offers considerations for study teams to think about as they design their risk plans, which adds another level of volatility in clinical trial risk assessments.

What is Consequently Happening in the Industry?

While TransCelerate’s methodology offers guidance regarding the process of developing RBM programs, the subsequent variability associated with the process introduces challenges with scaling up RBM in business operations and clinical technology functions. 

Individual study teams are defining their own risk assessments and methodologies, and based on the subjective focus of RACT’s categorical discussion questions, study teams are formulating unmeasurable and unquantifiable risk outcomes in clinical operations, which is seemingly adding to the confusion of operationalizing RbM on an enterprise level.  To elaborate, defining compound risk levels relative to Standard of Care applications is an unquantifiable factor from a clinical project management standpoint.  “If subjectivity were to be introduced in a manufacturing process, nobody would trust the final result and risk process,” said Peter Schiemann, Partner at Widler & Schiemann Ltd.  “When the study team changes, and risk assessments change, the risk interpretations and plans can be completely different,” added Schiemann. 

What Should RbM Standards Look Like in Clinical Trials?

The key towards establishing standards in clinical trial RbM is to not only understand quantifiable factors, but also factors that are applicable and standard towards clinical trials in general.  Medtronic, for example, implemented a toolkit of quantifiable and scalable risk assessments that were successful in evaluating site risk.  These analytical risk toolkits can be focused on a variety of risk objectives, such as enrollment performance, study endpoints, primary/secondary objectives, inclusion/exclusion criteria, protocol deviations, data quality and integrity, and even project management financial risks.  Building a general toolkit that can be applied towards all clinical trials in a variety of therapeutic areas can enhance standardization, consistency and quality outcomes during RBM execution.

What about differing therapeutic areas? It is important to emphasize that every therapeutic area will exhibit differentiating risk factors.  Correspondingly, risk assessments such as safety, and clinical trial failure prediction models will differ in varying therapeutic areas.  However, all trials share a large similarity, which can be exploited for standardization.  “Once standardizations are implemented, RBM should run like an engine,” indicated Schiemann.

History Repeating or a Shift in the RBM Paradigm?

Successfully deploying RBM across an organization is a challenge, as biopharmaceutical/medical device enterprises struggling to establish sufficient IT infrastructures for data streamlining, and are redefining roles and responsibilities.  Introducing subjectivity rather than standardization in RbM will only add to the confusion of RbM deployment.  Shouldn’t the industry start thinking in an objective and standardized manner?  “Clinical personnel are afraid to introduce standards because if standards are introduced, they’re no longer the ones calling the shots... everyone thinks that their trial is unique and therefore need to reinvent the wheel, and it’s counterproductive,” suggested Schiemann.