Dr Michael Silverman, principal at BioStrategics Consulting Ltd., talks about the necessity to view the success of a clinical trial from three very different perspectives, each of which has its own unique business implications, audience and role in resource allocation decision making.
In my previous blogs, I have talked about the importance of clinical trial end points, both in terms of the choice of measure, and as it relates to the phase of clinical development. I have also talked about the commercial considerations that need to be taken into account when designing a study. In this blog, I would like to explore three very divergent dimensions of clinical trial success. These three dimensions of success do not operate in isolation, but are closely interwoven throughout the course of drug development. They are:
- Strategic Success
- Scientific Success
- Operational Success
Strategic success incorporates those contributions that a given protocol makes to the organizations overall asset management strategy, as well as its role in advancing the compound’s clinical development strategy.
Asset Management: A biopharmaceutical company’s development pipeline is, in a very real sense, a collection of assets, even if they have not fully realized their potential. It is the responsibility of corporate management to maximize the value of these assets, through an asset management strategy or reasoned priority setting, targeted resource allocation, and efficient development activities. Every compound, every development program, competes for resources with every other program. The key to good priority setting and allocating resources is information: the crucial information being outcomes of data from pre clinical studies and clinical trials of products within a portfolio of drugs and studies. Which drug candidates show the most promising data, and are there enough drug candidates in each phase of study to support getting one through to approval? The audience here is clearly upper management.
Clinical Development Strategy: The clinical development process is mapped out with project milestones, decision points, go/no-go criteria, and contingency plans, and is the domain of management and its abilities to design the most appropriate work plan to obtain data necessary for regulatory approval and competitive data that will convince doctors of the drug’s safety and efficacy, patients of its therapeutic value, and payors of the overall health benefits, so as to maximize sales.
In the scientific dimension, we consider the biological and pharmacological principles that provide the scientific rationale for advancing a particular compound to the clinic. Endeavors in the scientific dimension aim to establish the underling biology of the new drug and how it translates into measurable and meaningful clinical benefit. Once sufficient data is available to support moving into clinical trials, then clear clinical protocol objectives are carefully written to express the scientific questions to be asked of the new drug in a particular clinical trial. The answers to these questions are critical to understanding the drugs activity in patients, its potential clinical utility and its optimum use in the target population. They also bear directly on the product’s eventual commercial success.
The operational dimension deals with the real nitty-gritty of the clinical trial, where the trial is initiated and implemented, where researchers collect patient data, complete and retrieve case report forms, create databases, and analyze results. It also involves randomization, blinding, and measurement, and also powering studies, collecting sufficient patients, staying on the timeline and within the budget. It is these areas that take considerable thought and careful planning as each one can make or break the success of the clinical trial. However, the primary objective of operational excellence in clinical research is to ensure the integrity of the trial data. Without accurate data that reliably and unequivocally reflect the patient’s clinical condition and the effect of drug upon it, the trial results are meaningless. Success in the operational dimension means the trial is conducted in a way that neither helps nor hinders the prospects of the drug; the product is allowed to stand or fall based on its own inherent attributes. To achieve this goal is to answer the question. But sometimes data integrity is not enough; many trials fail to answer the question posed, because they were not powered correctly, or insufficient thought was given to patient randomization or drop out. So to answer the question posed, one must also ensure that data sufficiency will be achieved to allow appropriate statistical analysis to be performed to arrive at an answer one can trust.
Strategic success, therefore, encompasses both positive and negative results as long as the results lead clearly to the next step in the asset management strategy, be it proceeding, terminating or switching priorities.
Scientific success means positive results that confirm the scientific hypothesis posed.
Operational success is contingent on the accuracy and reliability of the results and having sufficient data to perform one’s analysis.
I would be delighted to hear your thoughts on these issues, your approaches, or anecdotes about decisions you have faced in similar circumstances. To make comments or ask questions, click on this link.
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