The Nuts & Bolts of CRO Selectionneotrials.com/.../the_nuts__bolts_of_cro_selection-wp.pdf · 2018. 9. 16. · Oftentimes, a CRO will provide metrics on their experience in a relevant

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The Nuts & Bolts of CRO Selectionby Joelle HermanPresident & Principal Sr. Consultant of NeoTrials, LLC

100,000employed by the top 5 CRO’s

The CRO Outsourcing Trend. As companies continue to look for smarter ways to develop drugs, biologics, and devices, out-sourcing clinical trials to contract research organizations (CROs) and niche providers continues to grow. Today, nearly anything that a pharmaceutical, biotechnology or medical device business needs to do—from designing assays to planning and running clin-ical trials—can be outsourced to contract research organizations.CROs can provide full product development services and niche expertise by focusing on a particular service or stage of clinical development. They can serve to supplement life science companies’ limited manpower and be instrumental partners for progressing new therapeutics.

Outsourcing to CROs is undoubtedly a growing trend. About 15 years ago,

the top five CROs worldwide collectively employed

around 30,000 people. Now, that same group employs nearly 100,000 workers. It’s not unheard of for a single CRO to

have hundreds of clinical trials in progress at any

given time.

This burgeoning climate of outsourcing to CROs has many ramifications for the sponsoring organization. On the one hand, there have never been so many CROs to choose from. On the other hand, this cornucopia of

choices makes finding the right CRO for your company and culture more challenging.

Whether you are a large pharmaceutical company or a small biotech poised to initiate clinical trials, the CRO procurement process can be complex and daunting. However, the complexity of a successful CRO procurement can be managed with good early planning and a strategic approach.

This white paper will delve into several topics that will help organizations choose the right CRO for their program and culture and avoid the common costly mistakes that can derail the process.

ð Determining Internal Champions & Selection Committees

ð Strategic Sourcing and Procurement Workflow

ð Documentation & Regulations

ð Common Challenges

ð Best Practices to Get Best Value

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ShareVault and NeoTrials LLC The Nuts & Bolts of Selecting a CRO

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Determining Internal Champions & Selection Committees Not all CROs will be aligned with your

organizational culture, practices or expertise, so before going out and getting bids, the needs of the project need to be defined by an internal champion or selection committee.

A person closest to the science or, in a small company, the person managing the clinical trial is often best positioned to be the internal champion. The internal champion’s role is to coordinate the entire process and compose a committee that represents multiple functions (project management, medical, finance, clinical operations, etc.) for the purpose of determining the best outsourcing strategy. The internal champion will also be responsible for ensuring a process workflow, defining roles and responsibilities, identifying challenges and ensuring that selection criteria and goals are defined and agreed to by the selection committee.

Once the selection committee is formed and roles and responsibilities have been defined, it’s important to determine a timeline and define a communication strategy. This will ensure that the selection process is moving ahead

as planned and that all members are accountable for their roles and tasks.

One of the first tasks the selection committee will perform is identifying and agreeing on the resources and core assets within the organization that will be utilized and whether they will be supplemented with external resources.

After identifying the core assets to be utilized, the selection committee will identify the scope of the project including exactly what tasks the CRO will perform and which procedures and processes will govern various tasks.


Strategic Sourcing & Procurement Workflow Finding the right CRO for your organization and program should be approached at a strategic level. If you’ve contracted with CROs in the past, you likely already have a supplier or vendor network available to you. If not, the process for soliciting interest becomes more important.

The selection committee needs to decide on a fair and equitable process so that all parties can provide an informed and competitive bid. The process will likely be defined by the resources the organization already has, such as the company’s website, a vendor database, or contacts maintained by the company’s business development professionals.

Factors that can help narrow the field include market intelligence and an analysis of in-house skillsets

versus what needs to be acquired from outside the organization. It may also be necessary to consider incidence and prevalence of the disease under study. For example, will the patient group be localized or will it be necessary to find patients from all over the world? Sponsor companies employ target therapeutic area experts to elucidate the clinical plan, which allows for a narrowed focus of resource needs.

CRO Relational Outsourcing Models

It’s common for CROs to price their services using a time plus materials costing model, but these types of contracts put all the risk on the sponsor and do not incentivize the CRO to save money. A preferred model is a relational model that is based on risk and reward. There are three types of relational models to consider:

• Preferred Provider Model

• Performance-Based Model

• Vested Business Model

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1 2 3 Preferred Provider ModelA Preferred Provider is a vendor that has achieved priority status in the award of contracts by a company based on past performance. The Preferred Provider model is a long-term partnership that allows CROs to obtain repeat business and expand their business offerings. Working with a preferred provider allows the sponsor to bundle multiple studies, streamline business processes and reduce costs.

Performance-Based ModelThis model is based on key performance indicators (KPIs), but also the ability to drive improvements. Often value is achieved based on milestones, such as crossing regulatory hurdles or when the first site is activated. This model requires more collaboration and integration between the sponsor and the CRO and requires that the KPIs be realistic and well-defined. For example, if the CRO’s job is to find twenty sites, one milestone might be the time it takes to get the first site up and running and the second milestone might be the time it takes to get all the sites up and running.

Vested Business ModelIn a Vested Business Model the sponsor involves the CRO in the actual product development and rewards performance as well as novel ideas they bring to the table. A vested business model is a highly collaborative business relationship that serves to foster an environment in which innovation thrives, processes are improved, costs are reduced and both parties focus on shared value and goals.

CreateRFP

RFP Q/A

Invite Finalists for Bid

Defense

Contract with CRO

Send to Qualified

CRO’s

Score Proposals

Finalize Scoring

CRO Sourcing Workflow


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The request for information assessment (RFI) serves as a pre-qualification of the CRO or a niche service provider. The RFI ensures that the organization you’re choosing is meeting all the criteria that you’ve defined and serves to confirm that the organization can do what they say they can do.

All of these areas need to be audited prior to the execution of any agreement.

During the RFI assessment, an audit will be performed on almost every facet of the organization under consideration, including:

• Organizational chart, including office locations and services at each site

• Financial viability

• Insurance documentation

• Compliance with business ethics practices and inspection history

• Privacy policy

• Facilities

• Security

• Computer Management Systems (including backups and redundancy)

• Quality Management Systems

• Human Resources and Training

• Project Management (including SOPs and third-party vendor management)

• Specialty Services (Phase I Unit, EDC, Lab, Imaging, RIMS, Interactive Technologies, Packaging, Distribution, etc.

RFI Assessment / Prequalification of CRO


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Oftentimes, a CRO will provide metrics on their experience in a relevant specialty or therapeutic area, but metrics are just one element of their qualification. What needs to be evaluated is the larger picture of what uniquely qualifies them and what differentiates them to be able to perform this study and deliver as per expectations.

When a sponsor compiles a Request for Proposal (RFP) they’re providing everything a CRO will need in order to submit an informed and competitive bid, including:

R Background on the product or product development

R Guidelines for the proposal, including forms, deadlines and timelines

R CRO program deliverables

R A synopsis of protocol

R Program or project timelines, milestones, assumptions and expectations

R Roles and responsibilities

R Technical specifications for each area of service

R Specialty experience or past performance required

R Challenges identified by sponsor team and CRO recommendations

R Simple budget template (high-level)

R Evaluation criteria (financial and technical)

R Third-party vendors

RFP Checklist


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3.

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Have a Q&A ProcessDuring the RFP process, there is inevitably going to be a bit of back and forth. Even with the most compre-hensive and detailed RFP, questions and the need for clarifications are likely to arise. So, have a process for how the Q&A will work and ensure that it’s fair and equitable for all the parties involved. If a clarification is provided to one competing CRO, it should also be provided to the others. This is best done anonymously and with the same timeline for all.

Provide a Reasonable TimelineCROs should be given at least 15 to 20 business days to submit their proposal. Anything less and you’ll get something that’s generic, lacking detail, and doesn’t serve to help you make an informed decision. You won’t find the best fit CRO if you don’t give them a reasonable amount of time to put together a compre-hensive and competitive bid.

Communicate ChangesIt’s important to let CROs involved in the RFP process know when there are disruptions or changes in the program you’re conducting. Timelines can change. Safety or efficacy issues can arise. Development strat-egies can shift. In order to present the best proposal, CROs need to know the current status of the project.

Best Practices for the RFP Process


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The grid below is an example of how the roles and responsibilities of some of the technical specifications of a clinical trial can be defined.

Example Technical Specifications

Monitoring Sponsor CRO Comments

Perform SQV/SIV/IMV/SCV XSponsor may co- monitor as appropriate

Review eCRF against source 100%

X RBM expected

PVG Management Sponsor CRO Comments

SAE Management XCRO to provide database

Review SAE narratives X CRO PVG to draft

Submit SAE narratives to regulatory

X

Some of the differentiators that help narrow the field and allow for a positive and successful collaboration between parties include:

• CROs that are positioned to be a strategic partner

• CROs that are willing to share risk

• CROs that utilize applied innovation such as mobile technology, sensors, wearables, machine learning and automated electronic medical records (EMR)

• Flexible delivery—CROs that utilize risk-based monitoring (RBM) and Adaptive Trial Design

• Standard of Care—Does the CRO see the trial as a care option reducing the burden on the patient?

• CROs that utilize cloud-based solutions (virtual data rooms) that enable real-time integration and collaboration

• CROs with a track record of finding predictable site networks

• CROs with specialists who have the right skillset to add value

Narrowing the Field


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After completing the rigors of sending out the RFP, and selecting, qualifying and scoring candidates, you’ll likely have two or three CROs that meet your program criteria and are ready for further evaluation. As the candidates present their bid defense, it’s often helpful for sponsors to see simulations of the systems the CRO will be using. This creates a transparent process for the sponsor and gives them a hands-on feel for what they’re going to be experiencing over the course of the trial. This transparency can also identify both the risks and the opportunities with utilizing a particular CRO. Ultimately, the sponsor is looking for the unique operational tasks and processes that add value to their program.

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The DO’s of CRO SelectionManage the selection process by having a plan and creating a timeline. Make it formal so people are held accountable.

Look for alignment in culture, practice and expertise.

Ensure that the CROs representatives are transparent, responsive and receptive to a collaborative relationship.

Ask for key performance indicators (KPIs) and examples of timelines on similar projects and the challenges they’ve seen.

Have a fair and consistent evaluation process.

The Bid Defense


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Selection Criteria• Do you require a specific

therapeutic area or indication experience?

• Do you require specific team members to have indication experience?

• Is the CRO equipped to address your current challenges, such as understanding enrollment and feasibility? Do they have access to Key Opinion Leaders (KOLs) and investigative sites with the right population and experience?

• Are they responsive and do they have the ability to be flexible with internal and external processes and systems?

• Evaluate quality and consistency of performance as well as their financial stability and inspection history.

• Determine value. Is this the best service for the best price?

• Does the CRO operate with appropriate transparency?

• Is the CRO a willful collaborator and good communicator?

• How do they plan? Do they have project plans? Risk management plans? Monitoring plans? Statistical analysis plans? Data and pharmacovigilance plans?

When assessing a CRO for clinical operations, some typical areas to focus on include:

• Monitoring Plan Development (SQV, SIV, IMV, SCV techniques)

• Investigators and Sites Selection Process (KOL relationships)

• Informed Consent Process• Preparation of Study-

Specific Template• Review of Study Site Informed

Consent Form (ICF)

• Regulatory Documents Collection Process (Includes financial disclosure)

• Authorization and Process of Shipment of Clinical Supplies to a Study Site

• Trial Master File Management (paper or electronic?)

• Communication Plan

• Management Plan

• Quality Control Plan

• Business Operational and Geographic Issues

• Key Staff (Qualifications, Selection and Training)

Clinical Operations Assessment


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Example Scorecard

Scorecard Measure StandardsWeight

%Score (1-10)

CommentsMax Score

Organization 5% .5

Ownership/Chart/Locations/Employees cv’s provided

Maintains/tracks organizational own-ership chart, and em-ployees by location

5% 10 .5

Experience 20% 2

Team experience

Provided company metrics on expe-rience “x” studies. Provided cv’s of team proposed

20% 9MM does have “x”

experince1.8

Project Management 20% 2

SOPS/Plans/ Reporting

SOP list provided; example PM plan and monthly report provided

10% 10Incorporates third party

mgt.1

Issue Mgt.Appropriate commu-nication procedures and escalation

5% 5Escalation

unclear.25

EDC SimulationConducted a walk thru of systems to be used in trial

5% 9Thorough

presentation.45

Technical Service 35% 3.5

PM/DM/PVG/CO/Stats

In-house functions for most specifica-tions

35% 8Outsources

EDC (partner)2.8

Price 20% 8 1.6

Total 100% 8.4


After the bid defense meetings have been conducted and the selection committee has scored and finalized feedback, a winner is chosen and the other bidders are notified in writing. Other steps might include:

ð Additional information is requested

ð Scope is revised and finalized for bid winner

ð Sponsor receives a detailed budget and final Statement of Work (SOW)

ð Contract is reviewed

ð Contract is executed

Federal regulation 21 CFR 312.52 gives sponsors the ability to transfer any or all of the obligations of their drug development to a contract research organization. The regulation requires that any such transfer be described in writing and if all obligations are not transferred, the documentation must describe each of the obligations being assumed by the CRO. If all obligations are transferred, a general statement that all obligations have been transferred is acceptable. Any obligation not covered by the written description is deemed not to have been transferred.

A contract research organization that assumes any obligation of a sponsor must comply with the specific regulations applicable to the obligation and is subject to the same regulatory action as a sponsor for failure to comply with any obligation assumed under these regulations. Therefore, whenever the regulation references “the sponsor” it applies to the CRO for any obligation that it has assumed.

Finalize Selection Transfer of Obligations to a Contract Research Organization

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Lack of TransparencySponsors don’t always share their full development plans with CRO/niche providers or treat them as true collaborators, but transparency is important. When the CRO is fully involved in the planning process, they can often identify risk that the sponsor may not have thought of. The sponsor should have plans with the CRO that incorporate communication, governance, escalation, roles and responsibilities and identified risks and mitigation strategies.

Generalist versus SpecialistMany CROs have become generalists instead of specialists in a specific therapeutic area. The sponsor should identify early on what their needs are and whether the CROs they are evaluating have the expertise needed to accomplish their goals.

Dedicated ResourcesA common complaint sponsors have with CROs is that they’re not getting the time commitment they were expecting. This can lead to delays in the project and the perception that things aren’t getting done. It’s critical for sponsors and CROs to communicate expectations for timelines and to agree on timelines that are appropriate and realistic.

Lack of SpecificityVague specifications in the RFP inevitably lead to change orders or out of scope services. Change orders and out of scope services delay trials and increase costs. Upfront planning and detailed specifications result in better and more precise bids. Sponsors should be very specific regarding their goals and expectations for deliverables. Sponsors should also provide specific criteria for when a deliverable is accepted.

Challenges


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Sponsor Says CRO Says Solution

Inexperienced PMs with poor communication, clarity or

proactivity

Lack of planning or specifications

Define specifications and agreed acceptance criteria

Timlines slow or don’t allow for concurrent process

Unrealistic or push to meet the timelines

Define critical path and integration with resources

Decisions lack depthDecision-making impacts

quality (without CRO input)Utilize a partnership approach

in decision-making

Lack of resources; lack of training; poor quality;

turnover

Turnover of resources; bid and execution resource

disconnect

Define resources/RR/training/experience/transition planning

as part of the PM/RISK and Communication Plans

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Use tools that are cross functional for collaboration such as a virtual data room

Assess SOPs and do a skillset gap analysis for both organizations in order to optimize operations

Assess performance regularly (KPIs)

Define deliverable acceptance criteria

Identify, manage and have contingencies to mitigate risk

Identify and apply lessons learned throughout the project (at least once a year)

Best Practices for CRO Selection


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Q

Q

Q

A

A

A

Assume you’re a US-based company that has developed a malaria therapeutic. Is it better to source a CRO that is offshore or do you find one that is onshore that has sites they manage in countries like India or other places where that therapeutic needs to be tested?

It’s important to find a CRO that can operate and manage sites with those populations that are going to utilize the product. You have to consider where the incidence of the disease is and who is best suited to manage those sites with the suitable population. In most cases, it’s advantageous for the CRO to have boots on the ground in the regions where the product will be utilized and marketed. Local CROs can often have a huge impact with less costs than a CRO that is managing from afar.

What are some of the KPIs that are commonly used?

Typically, KPIs can be milestones based on cycle times. For example, how long it takes to open a site. How long the feasibility process takes. First patient in, last patient out. Time to database lock. How long it takes to write the CSR. How long it takes to activate a certain percentage of sites. Those are KPIs that should be measured and monitored on a regular basis. KPIs serve to manage the statement of work and tasks the CRO are performing.

You’ve been involved in many successful projects. Are there any notable projects that completely went off the rails?

I was working with a large biotech company that had contracted with a lab as part of their study. When the samples that were delivered to the lab where delivered they were re-labeled incorrectly with the lab’s label and all the samples got mixed up. Nobody knew if the samples sent for Patient A were for Patient A. It derailed the project for at least a week and caused a lot of havoc. It happened because the sponsor neglected to ask the lab about their procedures for what happens to a sample after it arrives at the lab and how is it managed.

Q&A

About Joelle Herman

About ShareVault

As President and Principal Sr. Consultant of NeoTrials LLC, Joelle brings over twenty years of experience in clinical product development. Prior to forming her own consulting firm, she served as Director of Clinical Operations for several biopharma companies. She has also been responsible for global clinical programs for US and non-US based organizations and began her career working with patients in cardiac surgery and a University Site Management Organization (SMO). Her trial experience includes pharmaceuticals, biologics, and medical devices with top biopharma. Joelle has conducted and managed over 30 global trials from medical devices to vaccines and has led trials for well-known products like Lipitor® and Flomax®.

Joelle is an expert in clinical operations, including global program management, investigational site management, vendor partnerships, outsourcing management, compliance management and has led many strategic initiatives to support private, public and government clients.

Joelle holds a Master of Public Health in Epidemiology and a Bachelor of Science in Microbiology, both from the University of South Florida and is a Certified PMI Project Management Professional.

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