Making the right choice

Clinical trials are an important part of the drug discovery process. Now, with these trials being outsourced, it is extremely important for sponsor pharmaceutical companies to find the right Clinical Research Organisation (CRO) to outsource to. Also, maintaining a mutually beneficial relationship with them will go a long way in the drug discovery process, explores Nandini Patwardhan.

Nobody can deny the fact that CROs play an important role in the process of drug discovery. "CROs play a major role in the drug discovery process. It is difficult for an organisation to maintain in-house, the vast resources and expertise required in the entire process of drug discovery. As a result reliance on CROs for regulatory controlled studies becomes inevitable," explains Dr Swaroop Kumar V V S, President, Drug Discovery and Clinical Development, Glenmark Pharmaceuticals.

"It is difficult for an organisation to maintain in-house, the vast resources and expertise required in the entire process of drug discovery. As a result reliance on CROs becomes inevitable" - Dr Swaroop Kumar V V S President, Drug Discovery and Clinical Development Glenmark Pharmaceuticals

This makes it all the more important for sponsors (pharmaceutical companies outsourcing clinical trials) to choose their outsourcing partners with utmost care and after doing their homework. The sponsor-CRO relationship starts with the former selecting a CRO and au contraire to the established norms, the relationship never ends. This is because CROs are not just service providers, they are the partners in drug discovery, and sponsors are realising this. "The role of CROs is in the process of development more than discovery. CROs play a critical role in determining the efficacy or otherwise of a new chemical entity," reveals Utkarsh Palnitkar, Partner Head, Business Advisory Services, Transaction Advisory Services, Ernst & Young. Hence the foundation of the sponsor-CRO relationship always starts with a lot of ground work followed by the actual selection process.

Selecting the partner

"CROs play a vital role in covering gaps in the capacity, widening the skill base and enhancing the drug development pipelines of the pharma company" - Utkarsh Palnitkar Health sciences Industry Leader Ernst & Young India

The selection process starts with the decision to outsource clinical trials. "Whilst most major pharmaceutical companies have in house departments that undertake all the processes undertaken by CROs, there is an increasing drive to outsource some portion of this activity," confirms Palnitkar. He further explains that amongst the key drivers influencing pharma companies to partner with CROs is the utilisation of external expertise to enhance their focus on core competency and an improved speed to market. "CROs play a vital role in covering gaps in the capacity, widening the skill base and enhancing the drug development pipelines of the pharma company," Palnitkar states.

Once a sponsor decides to engage the expert services of a CRO, it should go about designing and collating the specifications for the particular project. This exercise helps both, the sponsor and the CRO in understanding precisely, the requirements of the trials project and what is expected of the CRO. This helps in eliminating the problems of misinterpretation and lack of communication.

Once this is done, the CRO selection process will be a little clearer. "Normally, companies evaluate a CRO based on parameters like experience, quality, efficiency, speed and cost and pricing. And the selection process involves a comparative evaluation of the five parameters stated above," explains Kumar. They also look at parameters like relevant credentials in terms of clients served and/or projects undertaken, availability of the trained resources, status of infrastructure and linkages with hospitals and/or investigators and lastly, submissions made vs accepted by the regulatory authorities in US or UK.

Another important aspect of evaluating a CRO is by understanding the various compliances that they have. CROs generally need to obtain Good Clinical Practices (GCP) and Good Laboratory Practices (GLP) approvals from regulatory authorities. "This is in addition to the study being accepted and a successful audit, at some time during review, by an international regulatory body like the USFDA, UK MHRA and MCC," explains Kumar. This is because these approvals and certifications are a measure of the CRO's quality assurance standards and regulatory compliance. Not only this, an accredited infrastructure and standard operating procedures that are at par with global standards also assist today's CROs to attract and retain clients. This is especially relevant in terms of the acceptability of the data submitted to the regulatory authorities in the US or UK. Compliance with ICH norms, availability of GCP trained investigators, etc, enhances the credibility of the service provider," reiterates Palnitkar.

Once a sponsor zeroes down on a few CROs, then he can get quotes from them and conduct the due diligence on back of the above mentioned pointers. The due diligence, or the audit, as it is referred to in common parlance, is a two to three day activity conducted by the sponsor. Once the sponsor is satisfied with a few CROs, then it can make a detailed note, known as the request for proposal (RFP) and send to these chosen few. This RFP is like the holy grail of the Sponsor-CRO relationship. It is one document that outlines the sponsor's requirements in complete detail as well as the focus on various critical factors that will impact on the success of the project.

After the RFP is communicated to the pool of CROs, time should be given to them for coming up with a proposal. All the proposals received, should be reviewed objectively and a CRO should be chosen to partner with.

After deciding to partner with a particular CRO for a project, the sponsor should immediately kick-start the process of getting in place, a contract that comprises of mutually acceptable terms and conditions, meetings with the CRO partner to negotiate on those and finally close the deal. The sponsor should also be proactive in establishing a mechanism to monitor the entire project, measure performance of the CRO, note the deviations if any and measures to correct those and a formal mechanism to communicate to the CRO to give feedback or have a dialogue.

However, things do not end here, with the selection of a CRO. This is just the start of a long term partnership. Like any other strategic alliance—merger or an acquisition or a joint venture, this partnership is also fraught with its share of problems. It is up to the parties concerned as to how to resolve these move on the road to discovery.

Differing point of view

"Conflicts can arise due to lack of communication or because of misunderstanding of each others processes. They can also arise if the product in question does not meet the quality standards or if there is a mismatch of roles of the CRO and the sponsor," asserts A K Dasgupta, Managing Director, Lambda Labs. For instance, a sponsor may assume a CRO to undertake a process and a CRO may not do that because it is not mentioned in the service agreement. Also, conflicts can arise due the CRO’s inability to stay within the budget that was agreed upon earlier or to meet the fixed time schedules.

Not only this, several conflicts can arise between the sponsor and the CRO, relating to confidentiality, data protection, and ownership or sharing of intellectual property. "A sponsor may have an objection if the CRO has an ongoing engagement with the competitor of the sponsor, in terms of data protection or if the CRO is an off-shoot of a large pharma company who may be competing with the sponsor," discloses Palnitkar.

There are a number of reasons for conflicts to develop. For instance a CRO can err on account of its over-commitment or staff turnover, while a sponsor could err with a poor selection process or lapses in planning.

"Typical concerns arising from partnering can be effectively and sufficiently addressed through clear legal agreement and negotiation. Establishment of a comprehensive confidentiality/non-disclosure agreement (CDA), which covers the Intellectual Property (IP) of both the parties and also extends for a length of time sufficient to cover the sensitive nature of the information being disclosed would assist in deflecting any issues on confidentiality," states Palnitkar.

"Additionally, a pharmaceutical firm could also assess the potential 'conflict of interest' risks that may arise in each project, and structure CDAs and other agreements to address specific risks," he adds.

The CRO should also have employer-employee agreements in place to avoid any risks of confidentiality. It could further implement a business model, which would keep its involvement in conflicting assignments to a minimum.

Balancing act

The best way to resolve these conflicts is in the initial stages through regular monitoring of clinical trials. It is also of utmost importance for the sponsor to monitor the status of clinical trials to ensure compliance with timelines and processes. Any deviations from the standard processes could be rectified with timely intervention from the sponsor.

Another reason why monitoring clinical trials becomes extremely important is because the sponsor is the innovator. Hence, it makes sense that the sponsor guides the process of drug approval and usage.

The sponsor, thus have to be in control of the regulatory compliance of the CRO as well as of the scientific quality of data generated.

"Typically, sponsors have project management divisions co-ordinating the internal reviews and monitoring the progress of the trials. The process requires the involvement of not only the project management team, but also of the internal technical expertise," explains Swaroop Kumar. "Moreover, sponsors may recruit independent audit persons/firms to verify data authentication compliance upon completion of the trial," he continues.

Many of the conflicts can also be solved at an initial stage if the concerned parties devote sufficient time in preparing a detailed plan which identifies the possible threats in addition to conducting thorough risk/likely-failure analyses. Having back up plans will also go a long way to ensure trials are conducted efficiently.

"Clear understanding of each others scope of work and of the deliverables is the key to a long term and a harmonious partnership between the sponsor and the CRO," avers Dasgupta. He further states that the agreement or the contract between the CRO and the sponsor should clearly explain the role and its scope, played by the sponsor and the CRO, the objectives of the projects and relationship that will exist between them.

Further on, there should be a confidentiality clause, indemnification and responsibilities for each in crisis situation or 'nobody's fault cases' and public issues.

An ideal relationship between a sponsor and a CRO has to be of collaborative nature in order for a successful completion of the project in complete harmony, understanding and discussions between technical teams from both sides. "Hence a complete understanding of each others' processes, regular and undisrupted two-way communication between them and a moral responsibility to have 100 percent compliance can go a long way in building and reaping benefits from a sponsor-CRO partnership," avers Dasgupta.

A new product is like a small child passed on by the anxious sponsor, acting like a parent, to its CRO for nurturing. A clear understanding of each others roles and responsibilities can go a long in building a strong team that makes this product a strong brand.

editorial@expresspharmaoline.com