The PSDM group of the Biometrics Section (BMS) of the Netherlands Society for Statistics and Operations Research (VVS/OR) organised the event:

Risk-based Monitoring:
opportunities and challenges in clinical development

Monday September 2nd, 2013
hosted by Astellas, Leiden

Risk-based Monitoring: changing the position of Biometrics in clinical development


Current On-site Monitoring practices are frequency-based, conform to a prescribed monitoring visit schedule, and provide generalized quality control at investigational sites. Although this practice does provide a level of control, advances in risk-based approaches and technology provide an opportunity for a more holistic and proactive approach through Off-site and Central Monitoring and a targeted approach to On-site Monitoring (1). In 2011 both the FDA and EMA released guidance papers in which the Regulatory Agencies encourage implementation of modern, risk-based approaches for clinical study oversight activities, that focus on critical study parameters (2, 3). The almost concurrent release of the Agencies’ guidance documents has triggered numerous discussions among clinical research operatives and peers, including sponsors of drug and device clinical research, contract research organizations and academic clinical research organizations (4).

Technology, data integration, and analytics are all key enablers for successful implementation of risk-based monitoring strategies. Relevant analytics must be developed to enable rapid identification of outliers and trends in large volumes of data (1). Statistics and Data Management functions are therefore key to efficient risk-based monitoring approaches. This provides opportunities for our functions, but also requires a changing mindset towards the role of biometrics teams in the execution of a clinical study. Our speakers, experts and key opinion leaders in their field of work, will present their views on Risk-based monitoring approaches, current implementation practices and the role of biometrics therein. They will also discuss opportunities and challenges for our functions as well as for clinical development teams as a whole.

1) TransCelerate BioPharma Inc.; Position Paper: Risk-Based Monitoring Methodology; 30-May-2013
2) Food and Drug Administration; Guidance for Industry Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring; Draft Guidance 24-Aug-2011
3) European Medicines Agency; Reflection paper on risk based quality management in clinical trials; draft guidance 31-May-2011
4) eClinical Forum Risk Based Monitoring Taskforce; Risk-Based Approaches: best practice for ensuring clinical data quality; 15-Sep-2012


Final Program
(for abstracts and presentations see table)
12:30 Registration, coffee & tea
13:00 Case study: Risk-based Monitoring implementation – impact on Data Management and other functions & TransCelerate BioPharma initiative
Andy Lawton, Global Head of Data Management,Boehringer Ingelheim Ltd, United Kingdom

presentation PSDM – RBM event – 2 Sep 2013 – Andy Lawton

Andy Lawton
Global Head of Data Management,Boehringer Ingelheim Ltd, United KingdomCase study: Risk-based Monitoring implementation – impact on Data Management and other functions
TransCelerate BioPharma initiative




The first part of this presentation will examine an example of Risk Based Monitoring on a trial that has been conducted over the last 3 years, and the impact on all groups with particular emphasis on Data Management.
In the second part our speaker will cover the TransCelerate BioPharma ( initiative with particular focus on the Risk Based Monitoring stream and likely impact on industry.
Andy Lawton has a degree in Mathematics and Geology and over 42 years of experience working in computing, statistics and data management. Since 1984 he works at Boehringer Ingelheim, where he holds the position of Global Head of Clinical Data Management. Andy has utilized Risk Based Approaches in systems since mid ‘90s and in Clinical Trials since 2002.
Andy is very active in the Data Management and clinical development communities. He is one of the founding committee members of ACDM (Association for Clinical Data Management in the UK), as well as member of the TransCelerate RBA initiative. Andy has written numerous publications, including a paper with Dr Alistair Ross on GP Audit, which was the most quoted paper in the British Medical Journal throughout 80’s and 90’s.
14:00 Risk-Based Monitoring: from source data verification to source data review
Frederic Hlavac, Global Studies Manager,
F. Hoffmann-La Roche Ltd, Switzerland

presentation PSDM ndash RBM event – 2 Sep 2013 – Frederic Hlavac

Frederic HlavacGlobal Studies Manager, F. Hoffmann-La Roche Ltd, Switzerland

Risk-Based Monitoring: from source data verification to source data review
Risk-Based Monitoring (RBM) is not just about “monitoring” – it is a cross functional methodology for delivering quality data.
Even before the release of the FDA / EMEA draft guidance (2011), over the last several years, teams at Roche have been trying different, innovative, approaches locally and globally to re-think how monitoring activities are conducted.  The different initiatives led to a new RBM approach which was formally implemented 2 years ago at Roche. This new approach to fit for purpose monitoring is very much aligned with the recently issued TransCelerate BioPharma Inc position paper, reinforcing the need to build in “Quality by Design”. The key concepts are that cross functional teams will come together at the start of the study to assess the risk factors for a specific trial and will define the critical data and the underlying processes.  Coming to this understanding up-front allows operational teams to focus on what is important throughout the life of the trial. This new RBM approach tailors the monitoring activities to the study and site risk level, highlights the need for different approaches to centralised, remote and in-house monitoring activities and also reinforces the need for all functions involved in the end-to-end data collection and cleaning process to align and focus on high value activities around patient safety and study end points.
Frederic Hlavac has a PhD in Immunology and over 15 years of experience Clinical Trials in different Therapeutic Areas, including Oncology, Cardiovascular diseases and Metabolism. He has worked in both CRO and pharmaceutical companies as (Lead) CRA, Study Manager (on both country and global level) and Clinical Science Specialist. Currenty, Frederic is a Global Studies Manager within Roche’s headquarters in Basel.
Frederic is Subject Matter Expert for RBM within Roche, piloting the first phase of the risk-based monitoring initiative, which led to a new Monitoring SOP and Trial Monitoring Plan. He is fostering cross-functionality and go-simple approaches.
14:45 Coffee break
15:00 Detection of fraud and misconduct using statistical techniques
Hein Fennema, Director Late Development Statistics,
MSD, The Netherlands

Hein Fennema, Director Late Development Statistics, MSD, The Netherlands

Title: Detection of data irregularities
The development and approval for medicines is a complicated process involving a huge body of data. A key requirement for this process is that the quality of the data is impeccable. Over the years safeguards have been implemented on many levels, for example Good Clinical Practice, the introduction of standard operating procedures that are implemented to ensure quality, and audits performed by sponsors as well as well by regulators. In this presentation an actual case study of the discovery of data irregularities in a clinical trial will be presented, originating from the statistics department. This case is not only interesting in itself, but should also create an awareness of the importance of vigilance of all people involved in the development process, including statisticians.
Hein Fennema has a PhD in Social Sciences from the University of Nijmegen. He has 14 years of experience working in pharmaceutical statistics. Currently, he is Director Late Development Statistics at MSD.
Hein’s function includes leading a group of statisticians working in various indications, in particular the portfolio of legacy Organon products. Also he acts as statistical lead for late stage MSD products.
15:45 Plenary discussion: how will Risk-based monitoring change the field of biometrics and clinical development?
16.15 Annual PSDM Meeting
Egbert Biesheuvel, PSDM Chair
PSDM board members
17:00 Closure & Drinks

Hosted by Astellas, Leiden, the Netherlands.
Price: €50