Molecular Diagnostics
saving measures will accrue to pharmaceutical com- panies during their DDD process and include11:
i Timeframe: would be cut from current 10-12 years down to 5-7 years. ii Clinical trial patients per NDA: would be reduced from 5,175 to iii Cost: would be reduced from ~$1 billion now to iv Drug launch: would increase from current 5- 10% up to 25-50%.
Clearly the financial gains for the pharmaceuti- cal industry are potentially enormous and thus individual companies have a self interest in ensur- ing that they set up a combined DDD-CD process that is both efficient, cost-effective as well as a sus- tainable business model. The question that contin- ues to trouble the pharmaceutical companies is how to adequately value the CD from a monetary perspective as well as adequately control the process of CD development, and validation as it pertains to the drug product.
Companion Diagnostic company perspective Patrik Dahlen (CEO of Dako) has argued that a CD helps to provide “the right treatment for the right patient at the right time”12. This is a very similar sentiment expressed by Lauber and Averbush from Bristol Myers Squibb (BMS)9,10. While BMS and Dako have a signed partnership agreement in place, it is reflective of the broader fact that pharmaceutical companies and CD com- panies both agree in terms of what a CD might provide to the DDD process and ultimately the patient/consumer. Dahlen12 and other CD compa- nies13 have argued that their products provide sig- nificant value in the form of:
i Enabling targeted therapy by identifying potential responders to a specific drug. ii Facilitates differential diagnosis or identification of patient sub-sets. iii Identifies patients at risk for adverse events. iv Serves as an adjunct tool for monitoring response to therapy. v May aid in clinical trial design and reduce clini- cal trial costs. vi Permits data mining and re-evaluation of previ- ously studied drugs.
The perceived advantages defined by the CD companies and the pharmaceutical companies are striking in their similarity. However, there is less clarity and agreement on the monetary value of the
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CD when applied to the DDD process and patient/consumer outcomes.
In part this is due to the considerable difficulties of developing and commercialising diagnostics which are poorly understood14-16. This process is fraught with complexity at a number of different levels. Initially, you must plan for the clinical indi- cation and ensure that the specificity and sensitivi- ty requirements are in accord with whether you are developing a screening, staging, diagnostic, prog- nostic or predictive marker. The stability of the marker and facile/complex nature of the analytical technology platform used to perform the analyses must also be considered and planned. More recent- ly, there has been much debate about the value of a single marker or a multi-analyte approach16. Other issues to be considered include market size based on the end-user profile and the clinical indi- cation, as well as the regulatory approach to be taken. Once the initial discovery phase is complet- ed a time-consuming and costly validation process has to occur. You must consider ‘levels of evidence’ including patient accessibility as well as sample collection, storage and analysis. In addition, vali- dation must occur in two independent patient pop- ulations of sufficient size and you must demon- strate clinical validity and utility in terms of speci- ficity, sensitivity as well as positive and negative predictive value. Assuming that the validation study was positive, it is then necessary to navigate the turbid waters of the regulatory and commer- cialisation processes. Unlike the therapeutic drug process, regulation and commercialisation in the diagnostic sector are still maturing. For example a diagnostic can be CLIA compliant (often referred to as ‘home brew’), or an FDA compliant product. In the latter case this is achieved via either a 510k or PMA route. Finally, the diagnostic must satisfy certain criteria for clinical adoption. This includes, peer-reviewed publications demonstrating clinical utility, advocacy by key opinion leaders, inclusion in treatment guidelines by oversight groups, and inclusion by payors into acceptable technologies so that reimbursement can occur. All of this has recently been reviewed, detailed and summarised by Bender16.
This complex, time-consuming process is fraught with shifting regulatory oversight and ill- defined validation and commercial acceptance cri- teria. As might be predicted, the economic cost of such development and commercialisation is signif- icant. In the specific case of a CD, Stephen Little (recently the VP of Personalised Healthcare at Qiagen) has pointed out that “demonstrating clin- ical utility requires a clinical trial of both the drug
Drug Discovery World Summer 2010
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