OR WAIT null SECS
The four essential steps to ensuring optimal clinical deliverable specifications and process controls.
As the biopharmaceutical industry continues to move down an outsourcing path, it is essential that logical sourcing strategies and operational processes exist and align with corporate strategy. This alignment will ensure desired outcomes are realized, such as shorter timelines, enhanced trial enrollment, and reduced overall costs while maintaining quality. Sponsors are often so focused on specific clinical deliverables that they often overlook the essential need for sourcing strategies, detailed deliverable specifications along with robust operational and oversight processes. In a report by Booz & Company based on interviews with top-20 pharmaceutical companies, it found that while sponsor companies have expanded their level of outsourcing and embraced deeper and more integrated third party organization (TPO) relationships, sponsors have done so without carefully thinking through the necessary support mechanisms and without aligning their outsourcing and corporate strategies.1 This lack of proper planning and oversight can often lead to operational efficiency, quality, and regulatory issues as regulatory bodies are now heavily focused on TPO oversight. This article discusses the essential steps for developing and implementing a logical sourcing strategy.
Step 1: Developing a logical sourcing strategy (what is needed and when)
In order to have a truly logical and effective sourcing strategy, the sponsor must first have a clear understanding of its current and near future portfolio. This includes not only understanding therapeutic area needs, but also understanding the portfolio at the compound and trial levels, including trial volume and design. A logical sourcing strategy must be developed that provides flexibility in order to meet a variety of therapeutic study designs and compound-development needs while also ensuring consistency, quality, and timeliness of data and clinical processes, ultimately ensuring patient safety, data integrity, and the on-time delivery of the portfolio while controlling developmental costs.
A portfolio analysis is needed initially to develop the initial strategy, and then periodically in order to proactively plan and adjust the sourcing strategy as the portfolio changes. The analysis should be conducted over a suggested three-year time span in order to proactively set the sourcing plan and to ensure that the proper number and types of vendors are selected to meet the projected work volume. Contingency plans may easily be added to the overall strategy to buffer for any sudden portfolio shift. Critical trial criteria for successfully conducting the study need to be determined in order to fully understand the true clinical and sourcing needs for each trial type making up the portfolio. Trial types might include trial phase (IA, IB, IIA, III, etc.), trial size, complexity, specialty design needs (i.e., adaptive design) and registration needs.
The critical trial criteria might include clinical expertise, operational expertise, access to patients, investigator connectivity, site interface, recognized areas of therapeutic expertise, geographical presence, service capacity, timeliness, and strategic advantage. See Table 1 for an example of a critical trial criteria table.
Vendor and sourcing model analyses are now needed to align with the previously determined portfolio needs. Vendor models would include the larger, full-service contract research organization (CRO), the smaller specialized niche CRO, and the full-service clinical network. Sourcing models such as full (or project), functional (or process), and role-based sourcing also should be compared and aligned to the portfolio needs. The detailed analysis information needs to be collected using a request for information (RFI) process. It is crucial that a well-designed RFI document with specific questions measuring for critical trial criteria, cross-functional services, vendor capability, and capacity is utilized to ensure an accurate vendor and sourcing model analysis is performed.
Questions seeking the same information should also be placed in multiple sections of the RFI document to serve as an accuracy check. The RFI document should also include standardized definitions and data collection templates to ensure data entry consistency. The RFI data collection process should be a completely web-based process with data aggregation, filtering, and reporting functionality. The RFI should be reviewed by a cross-functional analysis team to ensure that an accurate vendor model analysis occurs in order to ensure optimal trial-model alignment within the overall strategy summary. See Table 2 for an example of a vendor capability table.
Analysis of the detailed portfolio and critical trial criteria data compared to the vendor capability data will allow for the preparation of a sourcing strategy summary including optimal vendor model types and target vendor pool numbers used to finalize the vendor pool. The vendor pool numbers are extremely important, ensuring that there are not too many vendors not allowing for steady stream utilization, but not too few in order to allow for portfolio/trial-need flexibility.
A Phase I/II adaptive design trial has very different needs compared to a large, global, Phase III registration trial. The summary should also be written in a user-friendly manner listing out the primary and secondary options or models by therapeutic area (if applicable) and trial type, along with a brief justification explaining the benefits and reasoning of the suggested options. To optimize use, the strategy summary needs to be converted into a very simple, user-friendly tool. Figures 1 and 2 below illustrate examples of a user-friendly, logical decision tree and a vendor selection consideration tree, respectively.
Step 2: Implementing using logical operational processes (how to make it happen)
In order to optimize the benefit of the sourcing strategy and ensure delivery of the portfolio, a logical operational process flow must be developed and implemented consistently across all study teams within the sponsor organization. The first key step in the process is the selection of an optimal TPO from the TPO pool based on the trial design or program needs. It is recommended that both a primary and secondary TPO choice be made in case the primary TPO choice has capacity issues or competing trials at that time. The selected TPO must be checked and verified for proper qualification dependent on which services are being outsourced. It is highly recommended that all TPOs or at least the core set of primary TPOs within the overall pool be periodically reviewed and qualified prior to being assigned a project in order to minimize trial startup delays. Periodic portfolio reviews are recommended and as the portfolio and sourcing strategy shifts, the TPO pool and qualifications may need to adjust as well.
Next, a request for proposal (RFP) packet must be compiled for the project. The RFP packet must include a draft or final protocol, detailed specifications and operational plan(s) dependent on the services being outsourced. These detailed documents are critical to ensure optimal TPO comprehension of service expectations, compliance, and ultimately delivery of the key deliverables. This includes the development of an accurate service budget/proposal to avoid future trial delays, issues, and change orders. Once the final contract and budget are negotiated and executed, the project kick off meeting may occur where the operational plan is further discussed along with the development of mutually agreed upon communication and risk plans. Communication flow is extremely important to ensure that the trials are implemented and managed in an effective and streamlined manner. Optimal flow would need to flow from function to function, sponsor to vendor, and from vendor to vendor, especially if functional/process sourcing is being utilized to ensure compliance with functional process requirements and to avoid duplication and other issues. The flow must also be coordinated and facilitated by one primary function (i.e., project management or external sourcing), though all functional areas will have partial ownership.
Recent publications have reported on a lot of dialogue and activity on many fronts on how to improve overall efficiencies in clinical trials and how sponsors may engage properly with their outsourcing partner(s) so that efficiencies and cost containment are a priority on both sides. Collaborative clinical/technical interactions between the select vendor pool and the sponsor need to occur. These interactions optimally need to occur at the portfolio, compound, and trial levels in order to ensure logical trial designs and trial placements occur for each compound that makes up the overall sponsor portfolio and to ensure a priority exists on both sides. Most sponsors only interact with their vendors at the trial level. In order to allow for proactive resource planning, the vendor-sponsor interactions need to occur at the portfolio and compound level.
Step 3: Measuring and maintaining through efficient control processes (how to ensure it truly happens and continues to happen)
Once the project services have been implemented, effective control processes must be put into place to ensure the deliverables are consistently delivered as specified in the contract. The first control process is efficient TPO oversight implemented in a manner to maximize quality while also minimizing sponsor and TPO staff impact to help control costs. An oversight plan will be needed to ensure consistent implementation across the sponsor staff.
Functional areas may need to develop separate oversight plans or a separate section within an overall plan to ensure their unique deliverable requirements are being met. Effective oversight needs to include both lagging and leading indicators. Lagging indicators would be used to measure historical results telling the sponsor how well the TPO has performed, while leading indicators would tell the sponsor if its sourcing strategy is effective and logical. Lagging indicators may include enrollment-to-plan and data-transfers-to-plan, while corresponding leading indicators might be number of initiated sites, countries with FPV, or outstanding monitoring visits (backlog).
Clinical processes can start to go wrong well before the TPO performance turns the lagging indicator red. It is crucial that the right indicators be measured, paired, and analyzed or investigated to tell an accurate performance story-and then acted upon in a timely manner by the sponsor to ensure the TPO is performing at a level to deliver the trial and justify continued inclusion into the select vendor pool. In addition, positive trends need to be continued through shared learning and negative trends mitigated through corrective action preventative action (CAPA) development.
Indicators must be standardized across all TPOs governed by the strategy in order to have fair and accurate cross-TPO performance analyses. Indicator categories might include site selection, regulatory readiness, enrollment to plan, financial,
dataflow, and compliance. In addition, it is recommended that an overall value model be developed and tracked along with the performance indicators looking at not only TPO performance, but TPO service fees and sponsor staff oversight that impact the overall value to the sponsor. The actual TPO service fees may be easily monitored by tracking the TPO invoices, while the actual sponsor staff oversight may be tracked using a time entry process (i.e., database, excel sheet) by service categories. The goal of the value model analysis is not to pick the least expensive TPOs, but rather the TPOs with the best overall value. Figure 3 above illustrates the typical vendor value model.
Two additional areas important to the overall oversight plan are quality/compliance management and TPO governance. Quality /compliance management would include ensuring that all TPOs within the TPO pool have been properly assessed prior to use for proper procedures being in place, staff qualifications, system validations, security, privacy, and other key requirements.
In order to ensure timely project initiations, the TPO pool must be qualified at all times and ready for use. To ensure this “state of readiness,” periodic reviews of the TPO pool, TPO services, service locations, and staffing must occur. These reviews could be incorporated into a periodic portfolio review, since the portfolio needs are directly correlated to the TPO pool needs. Thus, as the portfolio needs shift, the TPO pool would be reviewed, including TPO services, service locations, performance indicators, and need for additional assessments. Periodic checks for TPO service changes and needs for additional assessment could also be incorporated into the TPO audit cycle, which the sponsor’s quality department would periodically conduct usually based upon a risk-based approach. Quality indicators could also be added to the periodic performance reviews as an alert mechanism to the sponsor.
These alerts could be discussed at the TPO governance meetings, which are also part of the oversight plan. The key to having effective TPO governance is having the “right size” governance. Similar to performance indicators, excessive governance can be counter-productive, where the resource costs outweigh the benefit to the TPO and the sponsor. The key to determine the optimal level of governance is to have a risk management plan in place to determine the TPO’s relationship impact on the sponsor’s portfolio. Key risk factors to consider include work/project volume, service/project complexity and impact, safety and quality impact, budgetary impacts, and competitive advantages.
Typical TPO governance levels start at the project team operational level, focused on a specific project, and then escalating to the enterprise operational level, focused on multiple projects, and, finally, to the executive operational level, focused on strategic development and efficiency. All of the levels focus to some degree on relationship development. The level and intensity of governance (i.e., meeting frequency, length, committees, communication channels, etc.) all depends on the risk determination so that the “right size” is applied.
In order to have effective uptake and compliance to the oversight plan and control processes, it is crucial that a positive TPO relationship be maintained throughout the entire process. TPO relationship management is not easy, especially when managing multiple TPOs within the TPO pool. The key to a positive relationship is to create and maintain a collaborative environment between the sponsor and TPO staff. An effective communication plan and open channels are the first step to creating a collaborative environment, ensuring that both the TPO and sponsor staff is kept updated at all times, making them feel like an actual team member.
A collaborative approach should be utilized for the development of the final, standardized indicators, so that the TPOs feel they contributed to the development of logical and fair indicators. These indicators will allow for cross-TPO performance analysis in a de-identified, confidential format, and all trial or project work with the sponsor will be measured and analyzed in one standardized manner.
Not all TPO specific indicator suggestions or requests will be met; this point needs to be stressed during the collaborative development process. The performance indicators must be reviewed on a periodic basis (i.e., annually, biannually) and user feedback collected for definition and analysis criteria enhancements based on the actual cross-TPO performance trends from the previous performance period. In addition, as business processes change, performance indicators may require additional modifications to remain applicable and effective. A final point to stress on performance expectations and indicator development is that a sponsor should never expect more from a TPO’s performance than it would expect from their own performance.
Step 4: Replication using a logical document architecture (how to ensure it is all properly documented to allow for compliance and replication)
A logical, streamlined third party management (TPM) document architecture is essential to ensure optimal process and deliverable specification comprehension and, ultimately, efficient service delivery. All too often the sponsor will create very detailed, function-specific operational plans and other TPM governing documents in silos (i.e., in a specific functional areas like data management or statistical services) without consideration of other functional area impacts.
This cross-function oversight omission will often lead to conflicting process and specification conflicts. Excessive, duplicative details and content will often be included in the TPM document(s). Over time, as regulations, business processes, and requirements change-leading to needed document revisions-conflicting content will often arise as different functional areas update at different times and in different manners. These issues clearly illustrate the difference between having TPM documents versus a true TPM document architecture. A true architecture will consist of multiple standardized documents that are written in a manner to clearly define, govern, and manage both the work and relationship between the sponsor and the TPO. Each document that makes up the overall architecture must have a clear purpose and proper connectivity among the other documents. This will then allow for a logical hierarchy and standardized content landscape, helping to ensure optimal content comprehension and management.
So, how many TPM documents make up a logical architecture? The first step to developing a logical architecture hierarchy is listing out the key content categories such as privacy, confidentiality, escalation, governance, onboarding, training, and records management, as well as several other categories that need to be covered within the hierarchy. The category listing needs to be developed by a cross-functional team ensuring all functional needs are considered and based upon all TPM regulations, requirements, and applicable business processes to ensure overall compliance. Once the list is reviewed and confirmed by the functions, the next step is to determine the logical combinations and overall placement of the content categories to ensure wide accessibility and optimal user comprehension.
The overarching content landscape and hierarchy, including the logical number of documents, will then be finalized, always keeping accessibility, comprehension, and compliance in mind. Though architecture consistency across the TPOs is extremely important for optimal-user comprehension, not all TPO architectures may be exactly alike. Lower-volume TPOs may not require an extensive architecture, such as a high-volume TPO, and thus the sponsor needs to determine what approach is optimal for each TPO category, always keeping accessibility, comprehension, and compliance in mind.
Using the content landscape as a guide or road map, the cross-functional team would then need to focus on the development of logical architecture templates. It is essential that key instructions are written in a manner that is user-friendly and allows TPO relationship managers and study teams to convert the templates to TPO-specific and trial-specific documents. The standardized templates would be developed by functional area subject matter experts (SME). Once approved, a template owner would be assigned to each template in order to ensure the templates are periodically reviewed and the content maintained as regulations, requirements, and business processes change.
To help ensure proper architecture utilization, and maintenance, a content maintenance and change-control process must be implemented as the architecture is developed. These processes are crucial to ensure the architecture content does not gradually drift back into silos, ultimately leading to duplicative, conflicting, and ambiguous content. In addition, a TPO conversion checklist tool or process flow mapping all of the conversion tasks is highly recommended to help ensure consistent and compliant implementation. Once TPO-specific and trial-specific documents have been created and finalized, the TPO relationship manager (enterprise level) and study team (operational level) would be responsible for document content maintenance and periodic reviews. It is highly recommend that all periodic reviews and document content decisions are recorded and filed in the trial master file showing a complete decision trail and oversight, in case of future audits or inspections.
Centralized storage, maintenance, and accessibility are extremely important to ensure optimal architecture utilization and compliance across the sponsor and TPO staff. If staff is not able to easily access the key documents, then compliance will be negatively impacted, as well as inspection readiness. The end-user needs to know where to quickly obtain the most current version of the architecture documents and who to contact for assistance. Proper archival of previous document versions is also extremely important in order to have the ability to show the full document and oversight history. A centralized website with document management functionality, including proper metadata, which meets 21CFR Part11 requirements, is highly recommended. Proper account management and, thus, access to the site and site folders will also be important, so that sponsor staff may access all applicable documents while TPO staff may only access their TPO-specific documents for proper confidentiality. Site development and validation will be an important step to ensure all access and functionality is properly functioning.
During these changing times as the biopharmaceutical industry is facing increasing healthcare reform challenges, sponsors are quickly focusing on the development of a more efficient clinical research model, where sourcing is an essential and strategic component. Use of a strategic, collaborative approach, including management of a pre-qualified TPO pool all based upon the true portfolio needs, is essential. Sponsors must conduct ongoing portfolio and performance indicator reviews to adjust the strategy and TPO pool accordingly, while also enforcing the utilization of the strategy across the study teams and functions. Development and maintenance of proper control and oversight processes clearly defined in a logical document architecture will help to ensure ongoing utilization of the overall strategy.
1. Getz, K. “Peril and Promise of Risk Imbalance,” INSIDE Outsourcing - Guide to Strategic Outsourcing - Trends, Surveys, Analysis (10-16) (Dec., 2012).
Lee Scheible is an External Sourcing Relationship Manager (at the time of research); Chris Bodurow, PhD, is a Senior Director of External Sourcing; Karin Daun is a Director of External Sourcing (at the time of research); all with the Development Center of Excellence, Eli Lilly and Co.