The advantages of outsourcing clinical trials are numerous – from speed and efficiency to the ability to harness specialist skills and resources. A 2015 study by Research and Markets predicted that, by 2020, 72% of clinical trials would be outsourced to contract research organisations (CROs) – a leap from the 23% that were outsourced in 2012. With the overall responsibility for the quality of data remaining with the trial sponsor, however, the question of how to maintain best practice in collaboration with an outside organisation has to be a top priority.

This becomes ever more challenging as increasingly diverse data – drawn from social media, smartphones and medical devices, as well as traditional case report forms – make the task of managing clinical trial data more complex than ever before.

“Companies are now collecting quite a diverse, heterogenous set of data elements in a study,” commented Ken Getz, research associate professor and director at the Tufts Center for the Study of Drug Development, reflecting on a recent study on data management in the pharmaceutical industry conducted by the Tufts CSDD and Veeva Systems. “There’s data coming from so many different places that has to be integrated – often it’s coming from incompatible sources.”

Furthermore, the increased complexity and scope of contemporary clinical trials, combined with demands for greater speed and reduced costs, means that ensuring best practice in data management is at the same time challenging and absolutely vital to success. This is even more critical when a trial is outsourced to a CRO, and data must be shared between the sponsor and CRO.

Overall, the most important aspects of a smooth cooperation between a sponsor and a CRO are trust and communication.
 – Dr Johann Proeve, formerly of Bayer Healthcare

With these challenges in mind, consideration of how to optimise data management when outsourcing begins with the selection of the CRO to conduct the research: it must have the capabilities to deliver clean, reliable data. An existing relationship between the sponsor and CRO would mean that an understanding of expectations and practices already exists, making the generation of dependable data more likely. Beyond this, the sponsor would look for good clinical laboratory practice throughout the CRO testing process, assess whether further training is required, and judge if the CRO has the resources and logistical proficiency required to run the trial.

Effective collaboration between sponsor and CRO is at the heart of maintaining best practice in data management, and yet Contract Pharma’s 2018 Annual Outsourcing Survey found that only 25% of participants considered their relationship with a contract service provider to be a ‘partnership’.

The first stage in ensuring a smooth collective effort is communication. “Overall, the most important aspects of a smooth cooperation between a sponsor and a CRO are trust and communication,” said consultant Dr Johann Proeve, formerly head of global data management at Bayer Healthcare. “Trust is something that may take some time to grow. However, communication is something all involved parties should be able to apply to a cooperation without any specific training.”

Nevertheless, it is important to have steps in place to facilitate easy communication practices. This can comprise of meetings between the teams, including the sponsor’s data management team, from the very beginning of the process to establish common goals. These meetings also allow responsibilities and processes, the data-transfer agreement and key performance indicators (KPIs) to be defined and agreed upon upfront and at the contract stage.

The establishment of a formal communication plan that sets out when and how data-quality issues, milestones and information that should be shared allows transparency to be built into the project, with the level of oversight required by the sponsor understood and designed into the process. The use of schematics – such as Gantt charts – means that both involved organisations understand the trial targets and their corresponding time frames.

This upfront planning should also include a joint risk assessment, with contingency and risk-mitigation planning built in. A risk-based monitoring approach allows areas of high risk to be identified and subjected to higher levels of scrutiny. Training in good laboratory practice according to the standards required by the sponsor also contributes to the collection of clean and useable data.

Ideally, the data management strategy should be formulated with input from the sponsor and CRO, reducing the need for adjustments during the trial and creating cohesion that leads to personnel from the sponsor and the CRO feeling like one team – a true partnership. “An effective sponsor-CRO relationship is one in which the CRO team is seen as an extension of the sponsor team and the sponsor can capitalise on the respective abilities of internal and CRO personnel,” said Blake Jensen, speaking in his capacity as VP at Precision BioSciences (he became VP for quality and compliance at G1 Therapeutics in June). “Sponsors and CROs must work together and trust each other to maximise the efficiencies gained by outsourcing to clinical trial experts, while ensuring the sponsor maintains adequate oversight and is comfortable with the study’s progress.”

Collaboration between sponsor and CRO in the realm of data management can be greatly ameliorated through the use of technology. An electronic clinical data management system (CDMS) such as Oracle Clinical or Clintrial provides centralised communications, allowing easier oversight and reducing the risk of emails or letters going astray. A CDMS can generate reports for the sponsor and allow real-time access to trial data, while also creating a record of data management activities – essential for the audits required by regulatory standards. Best practice in this area, however, requires that the sponsor and CRO are familiar with the same software and that its users receive up-to-date training and technological support.

Good data management

The opportunity to facilitate good data management practice when outsourcing is enormous, but the industry has some way to go in this area. An endeavour to streamline the collaboration process is under way with the recent formation of Align Clinical CRO, an industry standards group made up of CROs, which intends to establish shared industry standards in technology.

“There is tremendous potential to enhance clinical trial execution with common technology standards that benefit the entire industry,” explained Henry Levy, the body’s president. “The assembly of Align Clinical CRO represents an important industry collaboration to improve the trial process and how the industry works in unison to accelerate development.”

Align Clinical CRO intends to publish an operational data exchange standard that would outline the components that technology companies can provide to facilitate the easy exchange of data between CROs and sponsors, with the intention of making clinical trials more time and cost-effective.

Time is of the essence when a trial’s data management can affect projected or subsequent milestones further along the process – something abundantly clear in the results of the Tufts CSDD and Veeva Systems clinical data management survey.

“One of the biggest surprises was our insight into some of the downstream effects of data management challenges, and how those actually affect the amount of time that it takes – for example, for the site personnel to enter patient data or even to the time frame from last patient last visit to the ability to lock the database,” Getz said.

Survey results

The survey showed database design causing hold-ups, with database release occurring after first patient first visit in 85% of cases. “Changes to the database design itself has an impact on that cycle time at the end of the study,” Getz explained. Best practice, therefore, requires database design to be flexible enough to accommodate variations in trials: validation testing must be carried out to make sure the database is fit for purpose.

The delays caused seem to be reduced when a sponsor also outsources the data management to the CRO. “CRO companies tend to actually be offering a speed advantage across most of the data management timeline: everything from the time to build and release of study data; for example, the study database, the time from the patient’s last visit to the database lock – the CRO tends to be faster,” Getz said.

The sense given by the Tufts CSDD and Veeva Systems survey is that the management of clinical data is currently at an important turning point, as the types of data included in a trial and the methods used to measure and manage it continue to rapidly develop. “We’re really just at the very start of the diversification of eclinical data that companies are going to have to manage,” Getz said. “We feel we’re right at the beginning of an evolutionary period here.”

Regulatory affairs outsourcing

The trend towards outsourcing in the pharmaceutical industry is not limited to the conduct of clinical trials or data management. A recent report by Future Market Insights (FMI) has projected an ongoing rise in the outsourcing of regulatory affairs.

The reasons for this development are numerous: an emphasis on research and development, the growing watchfulness of regulatory agencies and the increased documentation required in the conduct of activities such as clinical trials have all led to organisations to turn to external experts for their management of regulatory affairs. The services required include the writing of regulatory documents, the formulation of documents for clinical research and regulatory consulting, and legal representation.

The report – which covers the period 2017–25 – predicts regulatory writing and publishing to be the most popularly outsourced service, with a market share of over $800 million expected by the end of 2025. However, it also foresees the service with the fastest growth, at a compound annual growth rate (CAGR) of 14.3%, to be legal representation and regulatory consulting.

In total, the report expects the global healthcare regulatory affairs outsourcing market to grow at a CAGR of 12.2% and achieve market revenue of over $2 billion by the end of 2025. Of the expected end users, mid-size pharmaceutical companies take the largest share, with a market value rising from $270.8 million in 2017 to over $700 million by the end of the forecast period and a CAGR of 13.8%. Biotechnology companies are not far behind in projected growth, with an expected CAGR of 13.2%.

Source: FMI and GlobeNewswire