Fernando Geijo and Xavier Ruiz, manager of QA for R&D and QRD auditor, respectively, at Azbil Telstar discuss the importance of adopting good practices in clinical research.
Research
In 25 years of professional life in the field of quality in clinical research, the changes in this area have occurred mainly due to two factors: Regulatory changes and scientific advances; but a concern for costs always underlies these changes, increased in recent years by economic crises arising from international situations.
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.1
On the other hand, ISO 9001 is the internationally recognised quality standard which includes process improvement as one of its objectives. ISO 9001 requirements also include the need for the organisation to demonstrate compliance with statutory and regulatory requirements.2
These two approaches to quality systems show us that compliance with legal and regulatory requirements and process improvement are not incompatible; on the contrary, ensuring GCP compliance requires us to generate and have available an important volume of documentation and data, which, properly analysed, provide us with valuable information on the effectiveness and efficiency of our processes, that can be used to improve thereof. This consideration makes them complementary; furthermore, the effort and resources required for that analysis are small compared to the cost of a clinical trial and that small additional investment will be more than compensated as a result of process improvement.
Fernando Geijo
Telstar Formula
In our experience, this compliance/improvement approach has been used successfully generating improvements in compliance along with a decrease in costs.
Tools for the improvement
Analysis of monitoring results
Sometimes not explicit is that monitoring is also a quality control tool and sometimes the quality control steps associated with monitoring activities are poorly described.3
The link between the monitoring process and quality control must be sufficiently explained in the corresponding sponsor's SOPs and be a part of the essence of the monitoring plans.
There are two important aspects to consider:
The communication of the results of the monitoring activities and the mechanisms for scaling this information in the organization, ensuring that, depending on the result, it reaches the appropriate decision levels on each case.
The management of non-compliances should be managed in a similar way to the deviations in an audit.
Processes should be in place to ensure that root cause analyses are conducted where important deviations are discovered and that appropriate corrective and preventive actions are implemented to address issues identified by monitoring.4
Analysing the frequencies of the different types of monitoring findings and analysing their root causes, it can be inferred if the breaches are attributable to the site/investigator or to deficiencies/errors in the processes.3
Design of an appropriate quality system: Process mapping
According to GCP principles, the sponsor is responsible for implementing and maintaining quality assurance and quality control systems with written SOPs.1
This requirement is sometimes misinterpreted, especially by small organisations, such as start-ups, which subcontract almost 100% of the clinical research activity, which extrapolate the hiring to the fact that their quality system is not necessary, since they consider that they are not going to perform direct tasks within the clinical trial.
The first step to know the activity of an organisation is to identify and understand its processes in order to document them.
Process mapping will allow to define exactly how the organisation acts on each of the activities of a clinical trial, who is responsible for them, how a process should be completed and how conformity or nonconformity with the result is determined.
These tools, widely used in other sectors, are increasingly applied to the analysis of clinical research processes and serve as support for risk analysis activities as defined by regulatory authorities.3,4
Quantifying the Quality: Key Performance Indicators (KPIs)
Organisations are as effective and efficient as their processes and quality quantification is a tool for analysing them.
The quantitative measurement of the performance of the processes provides information about various aspects related to quality, such as:
- Evaluate the productivity of the people who performs them.
- Evaluate the benefits in terms of productivity and quality, from the use of new methods and tools.
- Detect improvement opportunities and define a baseline for estimating this improvement.
- To help identify training needs.
Key Performance Indicators are used in many areas to measure the processes of an organisation and as an instrument for quality improvement.5
Processes to be measured are selected analysing:
- Risks associated with each process related to included subjects in the trial, GCP non-compliances and business.
- Monitoring reports.
- Audit reports (if exist).
The metrics are defined considering:
- Criticality Analysis
- Type and frequency of discoveries have led to the selection of the process.
The scores for each factor of the metric are established considering the impact of each factor on the overall process.
It is worthy indicating that, along with a global quantitative measure of a process, probably the most interesting is the comparison between the results of:
- Different clinical trials,
- The clinical sites within the same trial,
- Different people running the same process.
Conclusions
The changing environment in which clinical research is involved invites new approaches to quality management.
Legal and regulatory requirements lead to the gathering of valuable information to improve efficiency and effectiveness beyond regulatory compliance.
The most current approaches to quality management systems are based on process evaluation. Process performance assessment and risk assessment are being introduced into daily monitoring and are taking on an important role in quality management systems in clinical research.
References
- ICH Harmonized Guideline Integrated Addendum to ICH E6(R1).
- ISO 9001:2015. Quality management systems – Requirements.
- Reflection Paper on Risk Based Quality Management in Clinical Trials. EMA/INS/GCP/394194/2011.
- FDA Guidance for Industry. Oversight of Clinical Investigations — A Risk-Based Approach to Monitoring (2013).
- 5. D. Parmenter, “Key Performance Indicators - Developing, Implementing, and Using Winning KPIs”. John Wiley & Sons (4th edition, 2020).