96 sites with local laboratories using site specific normal ranges? Nine different types of external data required in the study? Could you cope? Cmed did. Read how...

Cancer is second only to cardiovascular disease as the most common cause of death in the developed world. In fact, one in three people in the world will be diagnosed with cancer at some stage in their life, a statistic that puts the disease into perspective. As a result, every year billions of dollars are invested into oncology clinical studies across the world trying to tackle this growing global problem.

The last five years have seen a significant shift from the traditional endpoint oncology study designs
which saw patients either discontinue due to disease progression and/or in many cases death, to studies that evaluate secondary endpoints and introduce much more complex designs. Cmed have conducted over 70 oncology studies to date, and as a result, have become regarded as specialists in this challenging therapeutic area by their clients.

This case study presents a phase III randomised open-label study of dose level 1 versus dose level
2 of [Study drug] in newly diagnosed, untreated patients with chronic myeloid leukaemia in chronic
phase (CML-CP) using molecular endpoints as the key benchmark to evaluate efficacy in CML. Cmed commenced work on this study in March 2005.

Background of the Study

In chronic phase CML, cytogenetic response is usually considered as a critical goal. Historical
trials have shown this to be a meaningful endpoint for long term survival and critically progression-free survival. Despite very encouraging cytogenetic responses being achieved with some of the leading compounds currently being researched, the majority of patients still have minimal residual disease (MRD) detectable. In this context, “molecular response” is emerging as a very important benchmark for evaluating efficacy in CML.

Cmed were approached by the sponsor to perform the clinical data management of the study based on previous successful experiences working on a similar study in the development of the compound. The study presented some very clear challenges from the outset:

• The study would be truly global and incorporate 96 sites over 21 countries
• Each site would be performing local laboratory examinations using site specific normal ranges
• The study included numerous external data sources that would be processed by third party vendors that were even more critical to the success of the study than the data collected on the CRF

Cmed would use their own proprietary data management system (Timaeus) to manage all of the clinical data from this study, including all third party data.

Implementation

A key decision that Cmed had to make was resourcing the study in order to take advantage of existing therapeutic experience in-house. Cmed identified study leads with previous exposure to the studies indication and provided the whole DM team with specific disease training by external experts. This ensured the team had existing experience to refer to, but also a basic knowledge of the disease from the outset.

Cmed worked in conjunction with third party vendors to produce data specifications for all nine different types of external data required in the study. Cmed created the database within six weeks of final protocol available and started receiving paper CRFs and external electronic data in Aug 2005.

The Challenges of non-CRF data

Processing external data is a challenge to any organisation, especially performing reconciliation
between data sources in different locations. Often listings are created and manual reconciliation takes
place between visits, dates and times across CRF data and the data stored in third party datasets. There are many dangers that exist in this process, not only is it more difficult to spot erroneous
and missing data across datasets, identifying duplicate records can be very difficult and if left
undetected, will have serious consequences on the safety outputs. When oncology studies rely so heavily on this biomarker data, mistakes in the non-CRF data can be disastrous to the study, not to mention putting patient safety at risk.

The addition of numerous biochemistry and hematology ranges that need to be managed and updated throughout the lifetime of the study can be another challenge. If not managed smartly, normal ranges can be associated with the wrong results and for a CML study, erroneous ranges associated with hematology results can be the difference between a protocol violation and safety concern of the drug and an acceptable result.

Non-CRF data the Cmed way

Due to Cmed’s intelligent Data Acquisition and Management (iDAM) system Timaeus, the DM team were able to benefit from managing all of the clinical data in a single data repository, offering total data visibility across all datasets. Timaeus incorporates electronic data loaders which not only ensure that the right data is loaded into the database and presents it exactly where the assessment took place in relation to the CRF, but also performs automated reconciliations between the current CRF data and the electronic data, producing reports of reconciliation errors without loading erroneous data into the clinical database. This represented not only a much safer technique to perform the reconciliation, but also showed huge time and cost savings in relation to FTE requirements for reconciliation within the DM team.

Timaeus uses reference points that allowed the DM team to enter the blood chemistry and hematology
normal ranges within the database and compare the results with the normal ranges at point of entry. The reference points are fully customisable according to date, time, sex and even weight so processing and updating normal ranges was a painless exercise. Timaeus recognises which reference to apply to each individual laboratory results page automatically and provides users instant feedback on data quality by comparing the result to the normal range, thus reducing the potential for data entry error and point of entry.

Cmed also provides as standard, access to the clinical database in read-only format to the
client study team so not only could the data management team view all of the clinical data, the clinical team could view, run status reports and monitor metrics across the study inclusive of every single data aspect of the study, a term Cmed call “total clinical data visibility”.

Summary

The Cmed DM team profited from a robust user friendly single system to manage all of the clinical
data in a single repository which, through the efficiencies and smart operating methods Timaeus incorporates during the data management process, resulted in a clean and well organised process of dealing with the non-CRF data in the study.

The automated reconciliation checks ensured that the potential for duplication was eradicated and
provided both the DM team and the client immediate feedback on the quality of data being loaded. Because the electronic data was presented within the corresponding CRF visit, cross checking between
the electronic file and the CRF, including validation checking was a simple and painless process.

All of the efficiencies that Timaeus provided, coupled with the experience and professional
approach of the Cmed data management team, ensured the clinical database locked on schedule and avoided any of the potential obstacles that are often presented when working with non-CRF data.

Cmed clinical research services

Today, Cmed has performed over 300 studies, and currently employs over 250 people across Europe and North America.

Cmed has from the onset, established itself with two divisions; CRO Services and Technology.

The CRO Services division is able to deliver global projects and continues to go from strength to
strength. The technology division has developed the world’s first intelligent Data Acquisition and
Management (iDAM) system – capable of facilitating the collection, management and reporting of all data, from any source in a single database; seamlessly supporting site staff, clinical research
associates, data managers, project managers amongst others, in running clinical trials.

Cmed and Timaeus have developed an industry leading reputation for performing trials in these key business areas, to name just a few:

• A daptive Trial Design (ATD)
• E merging Markets – remote geographical areas, often in neglected diseases
• Early phase
• Oncology
• eSource Strategies

In December 2008, Cmed and GSK won “Best Technological Development in Clinical Trials Software Solutions” at GCPj annual awards ceremony, for their work in sub-Saharan Africa (Burkina Faso, Mali, Tanzania and Kenya).