Pharmaceutical R&D follows the concept of the Scientific Method, encompassing the following four major components (Figure 3):
Figure 3: Components of the scientific method
The essential framework of the scientific method as shown in Figure 3 includes: Observation leading to a hypothesis, then to experiments, data gathering, analysis, and finally results that accept, partially accept, or reject the hypothesis. To this framework important additions have been made, including the concepts of transparency and reproducibility, perhaps dating back nearly 1000 years when scientist Roger Bacon “conducted his experiments in precise detail, perhaps with the idea that others could reproduce and independently test his results.” 51
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Transparency, independent verification, and reproducibility are not widely practiced in for-profit pharma R&D, and therefore the current R&D process is in stark contrast to best practices in scientific research. As a result, the concept that optimal research should be transparent, reproducible, and conducted among the global community of scholars generally is not supported in for-profit medical research.
Proposed Open-Science Research and Development Paradigm
An open-science R&D (OSRD) paradigm as proposed in this research is not true “open-source” as understood by computer software developers and open- source drug discovery proponents. In a completely open-source R&D model, even patented information would be widely shared, including the molecular structure and means of synthesis.
Importantly, in the proposed open-science paradigm for pharma R&D, it is assumed that the discoverer and developer of the compound would still hold and keep proprietary any patent or patents, would fund R&D, and therefore could sell the drug or technology and seek profits if approved for marketing and distribution. The reasons for maintaining a patent-based, for-profit model are two-fold:
1. To maintain profitability for developers in order to allay concerns that substantial profit erosion would undermine funding for future R&D, thereby reducing innovation in medical research.
2. To modify the current open-source R&D paradigm to make it applicable for all pharmaceutical R&D, rather than only NTDs and orphan diseases where
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there is typically much less interest and investment from pharma. Therefore, an open-science process could have a much larger impact on global
population health in both the developed and less developed world.
The proposed open-science model for pharma R&D would not be completely open- source as the source (molecular structure and synthesis) would still be patent protected and proprietary. However, the process or “science” of developing a
molecule would be open and transparent, hence the proposed label, Open-Science Research and Development (OSRD).
The proposed OSRD process seeks to combine the concept of transparency and collaboration that is intertwined with the scientific method with the pharma R&D process. The underlying assumption is that the lack of transparency and
collaboration in R&D reduces quality and efficiency, perhaps to the point of being financially negative, and that the efficiency and quality gained by an OSRD process may overcome any loss of competitive advantage that proprietary R&D is intended to protect. In short, the question is whether it is possible that more transparency and collaboration in for-profit pharma R&D could, under certain circumstances, be
advantageous to patients as well as profitable to the pharma industry.
To understand what information would be made transparent in an OSRD process, first consider what is and is not open or shared in the current R&D model. During pharmaceutical discovery and development, the following information is kept proprietary as much as possible (Table 5):
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Table 5: Information typically patented and/or kept proprietary under the current pharmaceutical R&D paradigm
Molecular/Chemical Structure
Synthesis and Manufacturing Processes
Discovery process data such as in vitro laboratory testing (anti-viral activity, molecular binding, up and down-regulation of genes, computer modeling, etc.) Pre-clinical and Clinical Development Plans including Study Protocols
Pre-clinical research (study designs, raw data, analysis) Targeted Product Profiles, marketing research
o Animal toxicity
o Animal efficacy models when possible
o Mechanism of Action
Clinical research (study designs, raw data, analysis)
o Phase I (First-in-human, Clinical Pharmacology, etc.)
o Phase II (Dose-finding, Proof of Concept)
o Phase III (Efficacy)
o Phase IV (Post-marketing)
All correspondence with regulators, including meeting minutes
Costs related to drug discovery and development, manufacturing, marketing and distribution
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Most information and data described above are normally part of the Investigational New Drug (IND) application and are not obtainable under the Freedom of Information Act (FOI), even after the drug is approved.52 Some FDA materials and correspondence related to each drug candidate is discoverable after a drug has been approved, limited to parts of the actual New Drug Application (NDA) itself. Also, high-level results of some pre-clinical and clinical studies are often
presented at conferences or published in journals, but typically only if positive results are achieved. Such abstracts, presentations, and articles may contain rudimentary information on study designs and analyses, but are inadequate to allow independent verification of results.
The proposed OSRD paradigm proposes to make transparent much of what is kept proprietary as outlined in Table 5 above, with the following exceptions:
Molecular/Chemical Structure
Synthesis and Manufacturing Processes
Some Clinical Trial Data and Analysis (until after un-blinding of treatment assignment in controlled, blinded studies).
The purpose of keeping the first two items proprietary is so developers can protect the patents on their intellectual property and ultimately have a drug to sell if it is approved by regulators. Otherwise, other drug manufacturers could steal,
manufacture and market the drugs, perhaps in other countries with lower regulatory standards or enforcement. The purpose of keeping the third item proprietary until after un-blinding is to avoid introducing bias into comparative clinical trials.
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In the proposed OSRD process, all other information that makes up most of the IND and NDA, including study protocols, study data, analysis programs, IND safety updates, and written interactions with regulators, could be made available in an on- going fashion during the R&D process. Full and timely disclosure of most of the contents of the IND could be made a pre-requisite for filing the NDA, thereby truly opening up the R&D process.
In summary, this research examines whether an OSRD approach to pharmaceutical R&D could lead to better designed and more efficient drug
development plans and processes, resulting in better study designs, higher quality data and analysis, and lower R&D costs.
Research Questions
Primary Research Question:Overall, would an OSRD paradigm for pharma R&D be feasible and desirable in terms of process quality and efficiency, as defined by the key informants? Secondary Research Questions:
What are impressions of the current process of R&D in terms of process quality and efficiency?
Would OSRD have a positive, negative, or neutral impact on the quality of clinical research design, conduct, analysis, and results overall?
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Would OSRD have a positive, negative, or neutral impact on the efficiency (time and/or costs) of clinical research design, conduct, analysis, and results overall?
Regardless of whether or not the key informants support OSRD, do they recommend other and potentially better innovations applicable to pharma R&D?
What would the scientific, regulatory, legal, policy, financial and operational barriers be to implementing an OSRD approach?