OUTSOURCING CLINICAL TRIALS

Clinical trials are an integral part of drug development that decide the outcome of the newly developed or the newly formulated medicines. A well designed, planned and executed clinical study can bring success to an average drug molecule too, and a poorly designed or executed study can kill a promising molecule. Often, clinical trials are outsourced to CROs, may be end-to-end or a part of the study depending on the sponsor’s need. The sponsoring company outsources trials due to two primary reasons:(a)either the sponsor company does not have the required expertise to design, plan and execute a trial, or (b) does not have enough bandwidth to execute the trial. Many times, the sponsors are clear about the objectives and expectations from the trial, and they ask the selected CRO to design a study around those objectives and expectations. However, when the sponsors are not clear on the objectives or the expectations from their clinical trials, they ask the CRO to study and design the trial accordingly. Therefore, in either case, it is important to select an experienced, and eligible CRO to undertake a clinical trial project. This makes the selection of the CRO and the outsourcing of the clinical trial a critical and crucial affair.

The outsourcing of the clinical trial is challenging, and it is a skill. It is a process and not a one-time half an hour event. However, few sponsors think of outsourcing as an event and without a thorough evaluation of the CRO, make their decision in haste. Often such sponsors regret their selection which was based on selective criteria. The selection of the wrong outsourcing partner not only jeopardises the prospect of the molecule but also attracts a lot of troubleshootingwhich demands the sponsor’s time.To avoid such regrets and troubleshooting, the sponsor must clearly document the objectives and expectations of the proposed clinical study. This would help in evaluating the CROs and while there are no universal checklists, there are a few parameters and flags to look out for while making the selection. We will discuss these below, but before enlisting the criteria, let’s understand ‘outsourcing’. However, before enlisting the criteria for selection of the CRO, let's understand the outsourcing process.

Outsourcing usually starts when the medical or the outsourcing team is informed about the molecule and/or therapeutic category and the development timelines. Once this information is made available to the respective sponsor, the team studies the molecule, understands earlier data, and does an insightful literature search. Once all this data/information is available, the team decides the objectives, expectations and timelines for completion of the clinical phase. In the next step, the team starts searching the list of experienced CROs who can plan and execute the study in the given time frame. This is a general process and not necessarily followed by every company. Some of the smaller sponsor companies or generic companies start by searching for the CROs as soon as they decide on the molecule or the therapeutic area, and expect CROs to study, do the literature search and design the study. While searching the CROs, the sponsor team usually follows a fixed pattern, such as either:(a) approaching their preferred CROs, or (b) contacting known CROs having worked with them in past, or (c) contacting CROs suggested by a peer group or friends, or (d) Google the experienced CROs for the specific therapeutic area. Through these methods, the team gets the names of CROs, but not necessarily the ’right-fit’. However, due to time constraints, teams select the CRO from the list with limited knowledge. Every CRO indeed presents their best capabilities and expertise and promises completion of the study in the given time frame. A very common scenario which might have worked well in past for many of the projects. However, one can not befortunate all the time or necessarily have a well experienced CRO partner. Therefore, to avoid any error in identifying and selecting a CRO it’s important to follow the well-defined procedure and checklist.

How doesone select the ‘correct CRO’ for the study?

In any development program, the selection process of the CRO starts after receiving the name of the molecule, the therapeutic area, and the overall development timelines. The timelines for clinical development are derived based on the overall development timelines. In absence of a universal checklist for the selection of the CROs, one can use the following parameters proposed by the experienced  CRO and the sponsor’s personnel. These are general parameters and need to be redefined according to the need of individual project requirements.

1. Understanding the objectives/expectation, service required and the timelines for the study:

The first step before we start searching for a CRO is answering a few questions including: what do we want from our study? and why are we doing this study? There may be different reasons for doing the study: to evaluate the safety and efficacy both, or only efficacy, promotional study, to find the superiority over the comparator, to find the equivalence with the comparator, etc. Besides answering this, the sponsor needs to identify services that are to be outsourced. It is possible that few of the services required by the project can be done in-house, and/or only a few of those needs expertise from the CRO. Alternatively, could the entire project be outsourced? And lastly, the sponsor needs to define the completion timelines.

2. Have the list of CROs:

The identification of the list of experienced CROs and the understanding of the objectives or the expectations for the study can go in parallel. Once the name of the molecule and the therapeutic area are known one can easily start identifying the experienced CROs using various methodssuch as preferred vendor, referrals, secondary research or by the help of the search engines or specialised search engines which provide the ’right-fit’ list of CROs as per the requirements of the project. It is important to have a ready list of dependable CROs as it saves time when we are ready with all our understanding of the study of the product.

3. Understanding the service capabilities of identified CROs:

Once the list of the CROs is available, study them using their website or information available in the public domain, without contacting them directly. It is important to evaluate the service capabilities of the identified CROs and evaluate them based on required services from them. Not all the CROs have all service capabilities to offer, and if the project  demands end-to-end services then restrict your focus only to the CROs providing such services, or have multiple CROs with expertise in their respective domain.

After defining objectives, expectations, timelines, and understanding the capabilities of the identified CROs, prepare a blinded study synopsis and start contacting the identified CROs. Send them the blinded synopsis along with the request for proposal (RFP) document containing questions. It is important that all the CROs should be asked the same questions and should be evaluated on the same parameters. One can derive the questions based on the following parameters:

a. Details on the service capabilities

Ask service providers to provide their detailed service capabilities, including the number of employees, training of the employees, technology software in use, and overall experience. If the project is a planned multi-country project, ask the CRO about its capabilities to manage the study in different countries to understand the geographical coverage and knowledge of the CRO.

b. Understanding of the required therapeutic area

This is the most important criterion for evaluation of the CRO. Every CRO proclaims that they have experience in all therapeutic areas. It's possible to have the experience, but not necessarily the understanding of the required therapeutic area. Having experience and understanding are two different parameters. When the safety of the molecule is under discussion, an understanding of the therapeutic area is critical to avoid safety reporting errors. Therefore, proper questions need to be added to the RFP document to evaluate the therapeutic area understanding of the CRO.

c. Information on investigational sites and relationships with the investigators

Investigational sites are the backbone of clinical trials because completion of the trial is largely dependent on the enrolment of the trial subjects and the collection of accurate data. Therefore, CROs having a good database of investigational sites and good rapport with the Investigators can easily execute the site and complete the study in the given time frame. Hence there should be questions seeking information on investigational sites and the rapport with the investigators in the RFP document.

d. Project management capabilities

The CRO project manager is a key coordinator between Investigators, CRO senior management and the sponsor, whereas the project management is the process detailing the flow from the project planning to project completion. Therefore, while selecting a CRO one should critically evaluate the project management process, the experience of the project managers, and challenging situations/ risks handled by the project managers.

e. Quality management system (QMS)

Quality Management System varies from CRO to CRO and is mainly derived from the operational process and understanding of the process. Therefore, our expectations regarding quality need to be defined clearly in the RFP document so that all CROs will have a similar understanding of the requirements.

f. Statement of purpose (SOP) documents

SOPs are the guiding documents for the execution of the study, though the SOPs are categorised as confidential documents, one can ask for a list of SOPs from the CROs. Hence, the RFP should have questions on the list of SOPs for completing the required services.

g. Existing running projects

To understand the workload of the existing staff it is important to know and ask for some information on the existing projects maintaining confidentiality because every CRO works on optimum resource utilisation.

h. Software and other tools used

Technology plays an important role in the collection, compilation and analysis of various types of data in clinical trials. Technology assures timely completion of the clinical study. Therefore, the RFP document should have adequate questions on the technological capabilities of the CROs.

i. Financial Stability

It is important to understand the financial situation of the CRO because usually, the clinical study runs for a longer duration and changing CRO in between due to financial troubles would be difficult for the sponsors. Hence questions on financial stability such as how long the CRO is working in this space, existing clients, past clients, financial partners, etc. need to be asked in the RFP document.

j. Pricing

Pricing though may not be or should not be the only deciding factor in the selection of a CRO, but it is important to have a detailed pricing structure from the CRO. It is important to understand where the CRO service charges are visà- vis the market. As every CRO has a different way of presenting the pricing data, but to have a fair comparison between CROs the RFP document should have the questions designed uniformly, so that all CROs can answer with identical understanding.

Conclusion

Selection of the CRO can be a complex process if they are allowed to present their capabilities without defining your requirements. This is because every CRO has its way to showcase its capabilities, expertise, team strength, and pricing. However, if the sponsor can define the expectations and requirements in a RFP document the selection process becomes easy and faster. The presented list for parameters is just an example and is required to be modified as per the project demand.

--Issue 48--