If a pharmaceutical, biotech or medical device company outsources its clinical trials, it may be neither practical nor advisable to use one single Clinical Research Organization (CRO). Smaller CROs may not have the infrastructure to deliver large multinational trials, and large CROs may not offer the level of attention or flexibility required for smaller, but no less important, clinical studies. However, whilst the choice of CRO may be study dependent for the clinical aspects (such as patient recruitment, monitoring, clinical project management and regulatory expertise) there are tangible advantages to centralizing all data handling activities with a single provider – one that supports clinical data management, biostatistics, pharmacovigilance and medical writing services.
The benefits of centralized clinical data to sponsors are multi-fold: Centrally located data facilitates accessible data in a consistent format with consistent reporting. It makes the due diligence process for out-licensing opportunities much more stream-lined giving an additional level of confidence to the potential buyers. This added value does not come at an additional cost as it is based on building in efficiencies that are a cost-effective solution to the sponsor. A centralized infrastructure for clinical and safety data builds in quality by allowing for effective planning, communications and teamwork – something which can only benefit the clinical program.
Key financial benefits:
- Volume discounts can be obtained for Electronic Data Capture (EDC) licensing fees and centralized hosting;
- Using a central data management global library maximizes re-use of work from previous studies;
- Establishing sponsor-specific standard code libraries for statistical programming reduces the need to pay different CROs to re-invent the wheel;
- Ensuring all sites adopt the same EDC/ePRO technology reduces training and help desk costs;
- Using a central safety database ensures only one set-up fee;
- Using a single project manager for clinical data services can bring efficiencies across studies.
Key efficiencies:
- Effective cross-functional communications between data management, statistics and medical writing;
- Centralized study documentation facilitates more efficient editing, version control, auditing and information access;
- A central warehouse for your clinical and safety data avoids having to keep track of who has what and facilitates annual safety updates to regulatory authorities;
- A sponsor can have one web-based portal to access progress reports on all studies;
- Only one Master Services Agreement for data services required;
- The Serious Adverse Event (SAE) reconciliation effort is eased when the Case Report Form (CRF) data and the safety data are managed by the same organization;
- A project-specific medical writer can not only produce all required regulatory and clinical documents (such as protocols and clinical study reports), but also assist in publication planning, preparation and management of all of publication requirements;
- A single medical writing team with an appropriately experienced lead reviewer will ensure consistency across clinical and regulatory documentation as well as publications;
- Sponsors and regulatory authorities benefit from a straight forward audit trail that follows a similar path for all trials.
Providing a consistent team across multiple studies gives a single point of accountability and the foundation for successful project delivery. The sponsor can benefit from overarching advice from the CRO, starting with protocol design through to New Drug Application (NDA). A well co-ordinated team will reduce timescales and dovetail sequential tasks. This is particularly true of clinical programs where there are multiple trials on a single compound running in parallel. For example, the task of producing integrated summaries (ISS/ISE) becomes much simpler when all data have been generated to the same standards and formats, and are already centrally located.
The general perception used to be that a consistent team is not achievable using external providers. However, as outsourcing models have evolved this perception has changed. In many cases, CRO resources have become a flexible and scalable extension of a sponsor’s in-house team, and notably a team that does not require Human Resource investment. Critically, the CRO is able to establish standards by developing a thorough understanding of the sponsor’s goals, processes, quality systems, metrics and expectations. Identifying and maintaining a team with the appropriate therapeutic expertise and awareness of sponsor requirements throughout adds considerable value. For example, input from the same statisticians and medical writers at the study design stage to those who produce the final reports will help ensure submissions hold up to regulatory scrutiny.
Resource management technology within the CRO is a pre-requisite to cover demand planning, delivery management and scenario modeling. The sponsor needs to know that the CRO has the necessary capacity from week to week, and has a plan to ensure proper resource utilization. Such technology should allow estimates of the time required for each project task to be entered and the progress of each project milestone to be tracked.
Assuming there is transparency and trust with the CRO, centralization also creates an opportunity to move to a dedicated resourcing business model, whereby teams are ring-fenced for one sponsor only, and billed monthly at a fixed rate for agreed periods of time. While allowing the CRO to plan and maintain the same resource for that sponsor, it gives the sponsor the flexibility normally only feasible with an internal team. It also eliminates all administration attached to multiple contracts.
A ‘bundled’ approach, regardless of the pricing model, ensures there is no disconnection between data management, statistics and reporting. It reduces data processing time to maximize the delivery of high-quality data, on time and at a lower cost. This is exemplified by the following case study:
Quanticate Case Study
By working together and delivering studies as a coordinated biometrics study team, Quanticate was able to share knowledge across functions at the earliest stage of a program of oncology studies for a single sponsor. Through effective on-going communication, we successfully minimized any misunderstandings and potential re-work, provided the structure and organization to train other vendors involved with the studies on our processes, and implemented a successful partnership with our sponsor.
During setup of the first study, our statisticians were involved with protocol development and review of the Case Report Form (CRF) and Data Management Plan (DMP). They ensured these were in line with the objectives and endpoints of the study whilst authoring the Statistical Analysis Plan (SAP).
Our programmers reviewed these documents to ensure database structure and naming conventions were appropriate for producing outputs according to the sponsor’s standard conventions. Also, our medical writers aided with protocol development and reviewed the SAP, thereby having an in-depth understanding of the project in preparation for the reporting stage. Medical writing input and final review of the protocol and SAP ensures these documents are consistent with the requirements for production of the Clinical Study Report (CSR). The overall preparation time for the CSR is therefore reduced.
During this process, there was close liaison between the data management teams and our statisticians to assist in specific query handling, and to facilitate early identification of any data issues that required resolution.
Data cuts were provided to the reporting teams on an on-going basis and via ad hoc requests so that programming could start well before database lock and be close to finalization at that time.
Protocol violation, population determination and unblinding activities were managed internally and streamlined to minimize delay post-lock and ensure timely delivery of headline results. Our statisticians worked closely with the programming team to provide support for any queries and programming activities associated with key and complex analyses.
Our statisticians were closely involved with the medical writing team for preparation of the CSR in accordance with ICH guidelines. This reduced the time associated with CSR delivery and ensured the CSR reflected the inferences that were justifiable from the study results.
Quanticate’s medical writers had in-depth knowledge of the client’s reporting requirements, and were therefore in a unique position to provide guidance and educate the study team on the client’s standard CSR process; thus, reducing the potential for additional review cycles and minimizing deviations from standard processes.
Production of the CSR was on the critical path for regulatory reporting requirements (12 months from last subject last visit). The ‘bundled approach’ opened up lines of communication between the medical writer and the other functions early in the process, thus allowing work on the CSR to start before the timelines became critical, and thereby ensuring our client met their regulatory obligations.
All subsequent studies in the program were handled in a similar fashion, but with the added advantage of leverage from previous CRFs, familiarization with the sponsor’s requirements, and greater efficiency on time and cost.
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