Information Exchange

In recent years, biopharmaceutical companies have been facing stiff challenges as they conduct clinical trials – namely the concurrent needs of accelerating global studies, boosting operational efficiency and retaining strong relationships with stakeholders. Along with this, the complexities of clinical studies are increasing, as well as regulatory scrutiny. To manage these burdens, sponsors are reaching out to contract research organisations (CROs) using various strategic business models to share accountability and risk. As part of this effort, they are looking beyond traditional non-secure communication channels, such as fax, email and overnight mail, towards technology that can improve how the massive volume of information they generate is exchanged (1).

Fortunately, technology has advanced to the point where it can embrace electronic methods of collaborating confidential and critical information among partners. One approach is a hosted software-as-a-service (SaaS) solution that is intuitive and can exchange timely information related to start-up, study conduct and safety reporting in a secure, auditable manner. Forward-thinking companies are adopting this approach in an effort to fuel efficiency by reducing costs and time while improving quality.

This article takes a look at the complex environment in which clinical trials are conducted and the value in transitioning away from paper-clogged, manual processes in favour of SaaS-based solutions that better organise the exchange of information. There is also discussion on how SaaS-based solutions are key to the foundation needed to both strengthen the relationship with the investigator and build various strategic partnership models between sponsors and CROs. 


CURRENT LANDSCAPE

Conducting clinical trials is an intense process that is defined by tasks related to start-up, study conduct, safety reporting and study close out. From the beginning and throughout the trial, stakeholders – namely sponsors, CROs, investigative sites and institutional review boards (IRBs) or ethics committees (ECs) – need to complete and exchange an array of documents (see Table 1). Historically, this process has been paper-based, using fax or overnight delivery, or more recently, email, which is nonsecure and does not generate reliable audit trails. Information exchange becomes more complicated when paper documents must be sent globally as there are constant revisions, possibly creating confusion as to which version is the latest.

Recently, a survey of 252 investigative sites showed that 67 per cent of respondents report using unsecured email as the primary method of document exchange during clinical trials (2). The survey also found that 25 per cent of investigative sites state that they waste in excess of three hours each week hunting for study-related documents. Moreover, when asked how online tools might help with clinical trial document management, 27 per cent of survey participants indicated it would be easier to keep track of information.

Exchanging information via inefficient methods is costly and time-consuming, and as the clinical trial environment becomes more complicated, continuing with the status quo is increasingly unsustainable. To document the changing environment, the Tufts Center for the Study of Drug Development evaluated 10,038 protocols and found that they are becoming more complex (3,4). In the period from 2000 to 2003, there were, on average, 105.9 procedures per protocol. This number rose 49 per cent to 158.1 procedures in the period from 2004 to 2007. These changes mean that time-pressed investigators will need even more time to start, conduct and complete clinical studies. As a result, streamlining the exchange of study-related documents in a secure, auditable fashion becomes more essential.

Regulatory reporting requirements are on the rise too, creating more urgency for stakeholders to exchange regulatory documents in a timely manner. Specifically, on 28 March 2011, a new rule from the Food and Drug Administration (FDA) came into effect on drug safety reporting, whereby certain safety information that previously had not been required to be reported to the FDA must now be reported within 15 days of an occurrence (5). The intent of the new rule is to improve the quality of safety reports submitted to FDA through the use of internationally harmonised definitions and standards so that critical safety information about investigational drugs will be accurately and quickly reported to the agency. The new rule applies to all trials conducted under an investigational new drug (IND) application or as part of a generic drug application (6). 

In Europe, there are expedited reporting requirements for suspected unexpected serious adverse reactions (SUSARs) (7). They are to be reported to the central authority within seven days for fatal and life threatening SUSARs. All other SUSARS are to be reported within 15 days. The Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK has developed a website for SUSAR reporting and continues to update submission requirements (8). For example, from 1 September 2010, SUSAR submissions had to be made electronically, as non-electronic methods of SUSAR reporting were no longer accepted.

TECHNOLOGY – A LOOK AT THE CLOUD

By embracing secure web-based technologies, it is possible to improve communication among stakeholders while complying with the constantly tightening regulatory scene. The technology that makes this possible is rooted in cloud computing, a term that refers to the delivering of hosted services over the internet (9). Shared resources and software are available on-demand in the same way information is available to consumers on their smartphones through various applications or ‘apps’. This capability enables the rapid scaling up or down of computing resources in accordance with workload. A significant feature of cloud computing is that neither the sponsor nor the end user require local software installation. Only a device with a web browser and an internet connection are needed, allowing applications to be accessed from practically anywhere.

SaaS is one of the cloud computing models. In the SaaS model, the cloud is hosted centrally by an outsourced provider whosupplies the infrastructure and provides support 24/7/365. The user accesses the solution through a portal or dashboard. This approach frees companies from investing time, labour and financial resources in procuring, installing, maintaining and updating the technology.

Regarding clinical trials conduct specifically, SaaS-based solutions allow study team members to engage in document exchange in a way that is not possible with paper. The documents are stored online centrally and securely with the correct versions immediately available on a permissioned basis to the study team. In addition, they are searchable and provide a comprehensive audit trail. This is a dramatically different approach than exchanging paper documents as tracking is simplified, problems with versioning are eliminated, and it is possible to identify which documents are yet to be completed. These features enable study teams to accelerate study start-up and meet regulatory timelines for submission of safety information. They are also an important part of the strategic partnership infrastructure as stakeholders can engage in guided business process collaboration as they work toward common goals of accountability and results (see Table 2).

TECHNOLOGY FACILITATES STRATEGIC PARTNERSHIPS

Reaping the benefits of a SaaS-based platform is about more than improving the way documents are exchanged. It is mostly about strengthening the relationship with the investigator and enhancing communications and business process automation among stakeholders looking to create a new level of partnership. In the past few years, the clinical trials industry has been buzzing with conversation about re-thinking and re-evaluating outsourcing relationships into more effective partnerships, and technology has a significant role to play in this transition (10). But before describing how technology contributes to the partnership, it is important to explain how outsourcing has been changing and why. A detailed discussion of all aspects of this shift is beyond the scope of this article, but the following brief overview provides context.

Traditionally, in the life science sector, outsourcing to CROs has been tactical, meaning that a specific activity, such as clinical trial monitoring or clinical data management, has been performed by a provider. In large companies, these functions have typically been outsourced for study after study, meaning that each time a study launches, companies must engage in time-consuming requests for proposal in order to evaluate providers. As providers are selected and as studies unfold, each provider generally uses its own method of reporting to the sponsor, creating difficulties in consolidating and evaluating information from these disparate systems in a timely manner.

To reshape this fragmented picture and to gain competitive edge by accessing a provider’s resources, regulatory know-how and global reach, sponsors have been reconsidering the traditional model in favour of a more strategic approach (11,12). In the case of CROs, several business models for partnering have emerged and they are gaining traction as outsourcing continues to expand (13).

One of the approaches is known as the functional service provider (FSP) model. This method refers to the outsourcing of an entire portion of a clinical development process, such as a global Phase 3 programme or the managing of clinical research associates (CRAs) for a series of clinical trials, using the sponsor’s standard operating procedures (SOPs) (11). This approach differs from traditional tactical outsourcing as the scope of the FSP model extends beyond a single project. The intent is to decrease duplicative effort and fixed costs as resources are shared across multiple studies. As this model takes hold, the critical relationship between the sponsor and the investigator is typically maintained by the sponsor, and not outsourced.

The growing acceptance of the FSP model was recently discussed at the Clinical Outsourcing World Europe 2011 conference. Various presenters discussed how transitioning to an FSP model is completely transforming how they conduct clinical trials (14). They provided metrics documenting how reducing the number of outsourced providers across the globe has lowered costs, led to more on-time delivery of service, and decreased the number of non-enrolling sites. Importantly, when surveyed, investigators reported a positive view of these changes.

A second model – a full-service provider – may entail outsourcing a complete trial or programme to a CRO. In this scenario, the sponsor and CRO collaborate as strategic partners, with both having responsibility and accountability for deliverables. Typically, the sponsor is looking to the CRO for expanded operational capability, for scientific expertise, possibly in a therapeutic area that is new to the sponsor, or for management of specialty CROs or other providers. To be successful, the cultures between the two entities must be compatible, plus there has to be open communication and trust, and a mechanism for issue resolution. In addition, there needs to be in-depth discussion about the governance structure to carefully define the responsibilities of each partner.

This last factor – governance structure – is gaining attention as the industry faces increased regulatory scrutiny. As reported last year, the FDA is more aggressively enforcing regulations as evidenced by an increase in warning letters from the agency’s Division of Scientific Investigation, mostly to principal investigators (15). But recently, one was also issued to a CRO that was conducting clinical trials on behalf of a sponsor. This was a startling development and raises serious questions as to how sponsors should delegate clinical trial responsibilities to CROs when they form strategic partnerships and how those responsibilities should be outlined in the governance agreement.

As sponsors and CROs continue to define partnership agreements, technology has a key role to play in two of the factors linked to successful strategic partnerships:

• Communication among partners
• A harmonised and standardised set of technology and eClinical solutions (10)

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