Other than the straightforward use of utilizing existing companion diagnostic tests to sort patients in clinical studies, how are Contract Research Organizations (CROs) directly involved with their pharmaceutical / biotechnology clients (customers) in discovering, developing, or assessing tests relative companion diagnostics / personalized medicine?
CROs play a vital role in helping biotechnology and pharmaceutical companies develop companion diagnostics, assess them globally, serve as a liaison between the pharma/biotech company and the FDA to help speed up approval, engage and negotiate coverage for companion diagnostics with payers and help in the commercialization of companion diagnostic. Below, you will find more details about their role in companion diagnostics/personalized medicine.
CROs have various roles to play in developing companion diagnostic, although they are directly dependent on the ability of the CRO selected. To begin, the answer to your question on whether pharmaceutical/biotechnology companies use CRO laboratories when doing exploratory work to find likely CDx's or relationship between genes and biomarkers is yes, as evident by the fact that LabCorp, a leading CRO, "developed the companion diagnostic for trastuzumab 20 years ago." In addition, "LabCorp Diagnostics and Covance Drug Development have been involved in the development of companion diagnostics for cancers such as non-small cell lung cancer (NSCLC) and melanoma, as well as the clinical trials that supported FDA approval of such drugs."
More recent involvement in the development of CDx's by CRO is also exemplified by the fact that LabCorp Diagnostics and Covance Drug Development played a major role in "implementing companion diagnostics for immunotherapies involving the expression of PD-L1, with Covance Central Laboratory Services (CLS) exclusively responsible for testing specimens for PD-L1 expression on the registration trials for pembrolizumab and nivolumab, with LabCorp being the first to commercialize the specific tests."
The above examples show that CROs play a role in developing CDx's as well as in implementing and testing them. CROs help pharmaceuticals and biotechnology companies that have developed such assays to accelerate their speed to market by leveraging their scientific resources and global laboratory footprint. This is critical given the continued decline of clinical trial participants and the need for CROs to help reach a broader base with the necessary patient centricity that companion diagnostic assays require. In addition, pharmaceutical and biotechnology companies are increasingly trying to include companion diagnostics early in the drug development process to enable both drug and companion diagnostic to be evaluated in the same trial.
Personalized medicine is about the customization of medical treatment to the individual characteristics of each patient. This requires that each drug is tested on patients during the drug development process. The process from lab bench to the bedside is difficult and has several hurdles and challenges that must be surmounted. CROs help in overcoming these hurdles for pharmaceutical companies. And as location boundaries keep getting "blurred under globalization in the sciences and cross-border regulatory reviews," the advantage CROs with a global footprint and companion diagnostic expertise provide is increasingly evident. According to Mei-Shu Shih, "it has become increasingly obvious that CROs play pivotal roles in the chain of discovery/design, developing products to market through in vitro, in vivo, and ex vivo testing during preclinical experimentations and clinical trials."
For instance, Covalence was approached by a client that needed a CRO that could implement a specific assay globally and help them meet a tight sample processing timeline. Covalence already had the necessary equipment operational in the US and was able to rapidly deploy it in Geneva, Singapore, and Shangai through their facilities and network in those regions to meet their client's need.
A survey of experts from leading biotech and in vitro diagnostic companies revealed that they need CROs with "wide-ranging, fully integrated technical capability" that are agile and flexible and have a global footprint as well as detailed knowledge, experience and vision when developing companion diagnostics. Biotech/pharma companies increasingly rely on CROs that are capable of developing both the drug and the companion diagnostic assay.
Apart from playing the role as a one-stop shop where both the drug and companion diagnostic assays are developed, CROs also help in "providing clarity on the optimal use of a drug as well as the potential for differentiation in an increasingly crowded market." They also help in coordinating communication between the biotechnology or pharmaceutical company and the FDA, ensuring that drug approval is not delayed because of the lack of a companion diagnostic.
CROs also help in the commercialization of companion diagnostics. One essential aspect of this is making sure the companion diagnostic is ready for the market by ensuring that they are accessible, meaning that physicians are able to obtain results from the companion diagnostic assay within the timeframe required for the result to be meaningful. CROs help in this process and experienced ones are able to provide a practical road to market for such companion diagnostics. In addition, CROs also help engage payers upfront about the benefits of the companion diagnostics and help win coverage for it.
It is important to note that although pharmaceutical companies are turning to large diagnostic manufacturers and traditional Contract Research Organizations (CROs) to develop companion diagnostics, experts argue that these organizations have their limitations. For example, Philip D. Cotter, Deepti Babu, and Mathew W. Moore argue that neither large diagnostic manufacturers or traditional Contract Research Organizations (CROs) provide an entire solution. Their argument is that: "Diagnostics companies have an intrinsic bias toward internal product lines, and are therefore incentivized to direct diagnostics development toward an existing technology platform. The expertise of a CRO lies in the monitoring of pharmaceutical programs, not in diagnostics. In addition, few traditional partners have significant clinical laboratory experience or offer accredited clinical laboratories to ensure that the diagnostic clinical trials are designed for, and conducted in, laboratories that meet regulatory standards." The authors proposed a new concept, Contract Diagnostics Organization (CDO), in 2012 as a solution to the problem.
Hence, it is probably telling that CROs that have been successful in the companion diagnostic arena do have a combined Clinical Trial testing and Clinical Diagnostic organization such as that of Covance and LabCorp. So although CROs play a role in developing and assessing companion diagnostics/personalized medicine, only few CROs may be able to meet the challenge.
To wrap up, CROs play a role in helping to discover, develop, and assess companion diagnostic assays as well as help in commercialization and negotiation of coverage with payers for companion diagnostics.