Individual risk and population harm associated with smoking cigarettes may potentially be reduced by offering reduced-risk alternative products (RRPs)* to smokers.
The quality of the scientific substantiation of an RRP associated risk is of the foremost importance. INTERVALS will allow all relevant stakeholders to share the toxicity assessment data they have produced in relation to RRPs and alternative products, as well as the interpretation of the results they have obtained.
The last few decades have witnessed prominent voices articulate growing concerns on reproducibility in science. At the core of these concerns is the observation that subsequent attempts to replicate certain findings often lead to significantly different results. This problem—which appeared to increase in magnitude—was termed the replication crisis.
Among the culprits are the unprecedented rate at which scientific manuscripts are produced, the ever-growing size and interdisciplinary character of dataset acquisition, and the tremendous demand for computational power, often for a single experiment. All these factors have impinged on the reproducibility of scientific results and, at the same time, on the possibility to effectively peer-review manuscripts. Perhaps with even more dire consequences, the blueprint of this growing crisis also affects regulatory bodies, which need comprehensive and exhaustive access to all past and present research findings pertaining to the assessment of new products.
In an effort to address this problem, Philip Morris International R&D has created INTERVALS, a growing online platform open to scientists from both academia and industry, meant to enable third-party collaboration and data analysis. The website and the associated data warehouse are developed in collaboration with Emakina and Edelweiss Connect GmbH.
With a foundation built by using the latest standards in data sharing and reproducible research, the continuously updated INTERVALS is driven by the idea of proactive sharing of protocols, computational tools, and data from assessment
studies. In a single place, it shares results, software, raw data files, and detailed information on the design and protocols used in studies. This facilitates the review process and allows, at the same time, for the reuse of data for generating and
testing new hypotheses. We believe that all these traits enhance the transparency of the scientific process several fold and accelerate scientific research.
Initially, the platform was meant to present studies and share data from inhalation toxicology assessments. Owing to its continuous development, INTERVALS has evolved to include clinical study designs and results, various population studies, and even results from the fields of physics and chemistry. Although now enhanced, its core mission remains the same: to establish high standards for transparency and reproducibility by sharing data on scientific assessment of products.
In addition, the INTERVALS platform harbors basic research within the framework of systems biology—leading to a mechanistic understanding of diseases and pathways—as well as research on various aerosols and chemicals.
Taken together, these studies contribute significantly to the understanding of tobacco smoke-induced perturbations in human signaling pathways, detail the scientific assessment of new products, and represent an important step forward in addressing the reproducibility crisis in science by making data and software freely available.
The aforementioned mission of INTERVALS is in line with the vision of the 21st century toxicity testing established by The National Research Council following commission by the United States Environmental Protection Agency. This vision steers away from the sole use of traditional toxicity testing methods and calls for the study of adverse health effects sourced from induced perturbations in human signaling pathways by biologically active substances or their metabolites (Committee on Toxicity Testing and Assessment of Environmental Agents, 2007; Hartung, 2010; Krewski et al., 2010).
While INTERVALS was created as a platform for sharing (raw and processed) datasets and assessment results, the scientific community is invited to use the portal to share their own datasets and results and adhere to our vision of accelerated innovation through scientific transparency.
The portal allows users to browse the data by study, disease, pathway, endpoint, or product and obtain relevant information related to study design, methods, and, most importantly, results from preclinical as well as clinical studies.
The last two decades have seen an increase in scientific output and sharing of industry-sponsored and -conducted research, which is met with skepticism from the scientific community. Indeed, reports detailing concerns about data manipulation and misrepresentation have led to a decline in the credibility of industry-sponsored research. Engraved in public opinion, this lack of trust is damaging to innovation and makes the work of regulatory bodies even more difficult. In a now-landmark paper published in 2013, Bauchner and Fontanarosa presented a possible solution for restoring the credibility of the industry (Bauchner and Fontanarosa, 2013).
The INTERVALS platform has implemented the suggestions therein by:
Candidate and potential MRTPs are largely developed and, so far, assessed by tobacco companies. In order to establish the validity of the findings, the INTERVALS platform enables in-depth access to all scientific data and findings and acts as a study repository. Hence, the INTERVALS platform aims to complement the peer-review publication process by offering a comprehensive medium for sharing data, analyses, and software and to allow researchers to find all relevant information, detailed protocols, and, most importantly, interoperable data files to facilitate independent reanalysis of key findings, meta-analysis, and data reuse.
The current state of risk assessment employed for environmental toxicants and therapeutic drugs relies on correlative analyses performed within the framework of epidemiological studies that are run years or even decades after a product is released on the market or after a certain public policy is enacted. This state of affairs leads to irrecoverable delays, well past the point when a change in therapeutic regimen, lifestyle, or environmental exposure can prevent the onset of disease. In addition, post-hoc epidemiological studies do not aim to elucidate the mechanisms that link perturbations in molecular signaling to diseases.
One way to address these issues is to develop a computational approach capable of quantifying the risk posed by exposure to an active substance well in advance (Hoeng et al., 2012). To this end, the INTERVALS platform constitutes a gateway to a comprehensive data structure meant to provide a detailed picture of diseases, pathways, and interaction of active substances with tissues. It is intended to allow exploration of the Data Cube in relation to multiple biologically active substances that can constitute perturbations of biological networks, test systems, and samples.