Gerald L. Klein is co-founder of MedSurgPI.

Gerald L. Klein

	Biopharmaceutical and medical device companies of all sizes frequently outsource one or more aspects of their clinical trials. Outsourcing relationships range from tactical to strategic level partnerships with CROs and auxiliary vendors such as central laboratories, software solutions, imaging vendors and other services.

	Medium to large sponsors usually have in-house staff conducting CRO and vendor oversight with the guidance of their own company’s vendor selection and vendor oversight SOPs. Smaller companies typically do not have the resources to dedicate an employee or team of employees to this critical task. Employees at smaller companies are focused on discovery of new treatments and scientific innovation but often have both limited finances and experience in clinical trial operations. Yet the importance of overseeing and coordinating vendors and expertise needed for clinical trial success should never be overlooked.

	The stakes are higher now than ever before with skyrocketing costs of developing a single drug now estimated at $2.6 billion. The development process can take more than a decade and involve thousands of patients in clinical trials. Sponsors have the ultimate accountability for clinical trial compliance, conduct, budget, and ultimate success to bring new treatments to market for patients and investors or shareholders. Sponsors augment their capabilities by collaborating with CROs and other vendors with experience and expertise in the operations of clinical trials.

	Access to the expertise of CROs and other vendors enables sponsors to augment their resource on demand and without carrying the full burden of large departments of personnel. However, since the sponsor has the ultimate accountability over the compliance, conduct, and budget of the clinical trial, the sponsor must put in place mechanisms for oversight of the deliverables, including recording of adverse events, enrollment, expenses, and so forth.

	Often, a single clinical trial is the “make or break” milestone of a biopharmaceutical company. In fact, the survival of the company may depend on successfully achieving clinical trial milestones to validate the next financial investment. Lack of adequate oversight can introduce a fatal flaw in the integrity and outcome of that trial. 

	Small sponsors frequently depend on external funding from venture capital, private equity, government grants, or larger sponsor partnerships. While all sponsors want to conserve resources and be cost-effective, small sponsors with limited and tenuous funding may take shortcuts to preserve financial resources. This can lead to shortcuts in vendor oversight and management, which may prove costly to the success of the trial.   

	Experience has demonstrated that modifications to clinical trial plans is common. Changes may be simple modifications, such as clarifying instructions. Or they may be significant, such as modifications to the study design.

	Even when progress is running smoothly with vendors, advice to shift strategies is sometimes introduced from newly hired C-suite executives, funding partners, and consultants. Even small shifts in direction for sponsors requires a thorough and robust process for change management and collaboration with all vendors.

	Navigating change requires dialogue with each vendor to understand and communicate downstream implications. Change, even when it is positive, is also financially costly when vendors are not fully coordinated.

	Breakdowns in communication and coordination foster most outsourcing challenges for small sponsors, according to a recent informal poll by Edgerton Data Consulting of five small sponsors. All five responders felt their low volume of work compared with the larger annual revenue of big CROs and vendors meant their trial did not get the priority and attention of bigger sponsors’ trials. This lower level of attention manifested in several ways to the detriment of the smaller company’s success such as:  

		Not informed of study progress or risks to timeline and budget. 

		Vendor’s deliverables did not have adequate quality oversight. For example, one sponsor reported that the CRO’s Statistical Analysis Plan (SAP) more closely resembled a SAP template than a draft of a study-specific SAP. 

		Insufficient coordination and alignment with other vendors.

		Rigid vendor processes did not have adequate flexibility for the ever shifting priorities of the small sponsor. 

		Vendor staff turnover. It was not uncommon for sponsors to experience key vendor staff turnover multiple times in clinical trials of only six months.  

	All these challenges can lead to handoff issues, wrong decisions, and increased risks to investigational product (IP), subjects, and trial integrity. Obviously, these issues may also carry substantial cost implications.

1. Initiate a foundation for success with vendor selection.

	If sponsors don’t have the expertise in-house, it is vital to hire a consultant to supplement your team in order to fully vet the vendors for areas of primary importance to your clinical development program.

	In the Request-for-Proposal (RFP), ask the vendor about experience working with small sponsors. Also fully explore the vendor’s process for keeping sponsors informed and managing changes in scope, quality control of deliverables, cost containment, and key staff transitions. Ask for examples for each situation.

	Sponsors should request that the proposed members of the project team per RFP attend the bid defense as an opportunity to build engagement and set expectations with the team that will execute the project. Be wary of vendors that bring more staff to the bid defense meeting than sponsors have in the room. This may reflect lack of accountability for non-billable expenses, which ultimately are paid for by the sponsor. It may also demonstrate a lack of current work or lack of concern for the current responsibilities staff have that are interrupted by attending the bid defense.

	Finally, but perhaps even more importantly, examine responses in context of whether there is a cultural fit.

2. Strengthen the foundation with a solid contract.

	The Scope of Work (SOW) generally lists the major tasks and deliverables in the clinical trial in the form of a matrix for who (vendor or sponsor) performs and approves each task or deliverable. Sponsors should modify this by adding timelines for quality deliverables. For example, if it is important to have top-line trial results before a scheduled therapeutic area conference, agree on the number of days from database lock for top-line tables, listing and figures (TLF) delivery.  

		A similar expectation can be communicated regarding change-in-scopes. 

		Define what constitutes real scope changes

		Identify who can approve them and whether there are thresholds in cost level requiring additional approvals

		Define how scope changes will be tracked 

	For example, will each and every change have to be approved before implementation or can the sponsor and vendor agree on a level of cost that comfortably allows the vendor to work while the sponsor in good faith proceeds with scope change approvals? Also, be clear about who will be doing the work. If portions of the work are to be subcontracted by the vendor, the sponsor may want to provide approval first.

3. Maintain a strong foundation with oversight.

	There is fine line between effective vendor oversight and costly micromanaging. The sponsor’s primary goal is to clearly communicate the path for mutual success. Vendors strive to comply with sponsor expectations and requirements. Sponsor oversight is one way vendors can stay on track and avoid uncomfortable conversations later due to miscommunication.

	To accomplish this goal, the sponsor should provide an expert resource to serve as the sponsor project manager for all clinical trial activities. This resource can build engagement with the vendor team by attending and managing project team meetings and ensuring the sponsor team is an active participant in all aspects of the trial, such as development and approval of the protocol and all study plans. This includes case report forms and monitoring reports; user acceptance testing of tools such as the electronic data capture system; and critical review of study report, tables/listings/figures shells. 

	Small sponsors who do not have a qualified internal resource to serve as the project manager to provide adequate vendor oversight should seriously consider hiring an experienced contractor to supplement their team. The goal of everyone involved is a successful clinical trial. Clear communication and effective coordination will ensure the best results possible.

Articles

Executives from Edgerton Data Consulting and MedSurgPI discuss biopharmaceutical and medical device companies outsourcing one or more aspects of their clinical trials. 



Gerald L. Klein

Articles

The Case for Vendor Oversight for Small Sponsors