Introduction
The Therapeutics Research Institute, a 501(c)(3) nonprofit corporation located in Saint Davids Pennsylvania, was initiated in August 2012 to examine and report on various aspects of modern therapeutics. Its website, TRI-institute.org, which contains all its reports and commentaries, became operational in August 2014.
Objectives
The objectives of the Therapeutics Research Institute (TRI-institute), which are listed at TRI-institute.org/Organization, are:
- To conduct scientific assessments of characteristics of drug treatments of human diseases based on available information and relevant frameworks;
- To analyze and report such findings by indications and therapeutic areas, pharmacological mechanisms, types of endpoints, and disease types;
- To co-sponsor seminars, particularly in the Greater Philadelphia region, directed at the pharmaceutical startup community, exploring lessons from the findings; and
- To engage in other activities related to the objectives of the corporation, that will further its mission.
Current Projects
High-level outlines of the three current projects, Progression of Modern Therapeutics, Characteristics of Therapeutic Response, and Systems Therapeutics, are shown on the graph below (click here for a larger graph).
Update on Current Projects
A summary Update on Current Projects, for the three current projects, are shown on the graph below (click here for a larger graph). The dates of individual reports and posts (month, year) are also shown, except those for the 17 commentaries on individual therapeutic classes.
Examples from Recent Work
Below are three examples from recent work, i.e., from one of the 17 commentaries on individual therapeutic classes, from an analysis of the number pf pharmacologic classes per therapeutic classes and the number of approved new molecules per pharmacologic classes, and on an updated diagram on systems therapeutis.
New Drug Molecules for Osteoporosis
Above is a chart from one of the 17 posted commentaries on individual therapeutic classes, which had originally been included in Progression of Modern Therapeutics (2015 Report), this one on approved modern therapeutics for osteoporosis, from Osteoporosis: Better Drugs and Better Scientific Understanding Needed (July 2016). These commentaries have included, to name a few, Irritable Bowel Syndrome (September 2016), Benign Prostatic Hyperplasia (August 2016), Migraine (December 2015), Rheumatoid Arthritis (October 2015) and Lipid Lowering Drugs (September 2015).
Regarding osteoporosis, since 1984, a total of 9 new drug molecules have been approved for osteoporosis, in 5 pharmacologic classes. The 1995 approval of Fosamax (alendronate), the first of 4 approved bisphosphonates, represented an important milestone for this therapeutic class. The other 4 pharmacologic classes involve the SERM’s (Selective Estrogen Receptor Modulators), calcitonins, parathyroid analogs, and RANK (Receptor Activator of Nuclear factor Kappa-B) ligand. It was also commented on concerns about bone quality and the effects current osteoporosis drugs may have on bone quality, and that a new FDA draft guidance called for additional long-term nonclinical pharmacology studies (bone quality studies) to support new osteoporosis drug development.
Number of Pharmacologic Classes per Therapeutic Classes
The above chart shows the number of modern therapeutics’ pharmacologic classes per 38 of the 40 therapeutic classes covered in Progression of Modern Therapeutics (2015 Report), from Great Variability in New Drug Approvals Among Pharmacologic Classes and Therapeutic Classes (February 2016). This graph illustrates the significant variability in the number of pharmacologic classes per therapeutic classes, ranging from as high as 11 for Type-2 Diabetes to 1 for Systemic Lupus Erythematosus and Idiopathic Thrombocytopenic Purpura. Note the mean and median values for the number of pharmacologic classes per therapeutic classes were 4.3 and 4, respectively. The same commentary also showed a wide range in the total number of new drug approvals for these therapeutic classes, ranging from 44 for Hypertension to 1 for Systemic Lupus Erythematosus; note he mean and median values for the number of new drug approvals for these therapeutic classes were 11.5 and 9.5, respectively.
Systems Therapeutics
Above is the recently updated systems therapeutics diagram, from Systems Therapeutics: Updated Diagram (October 2016). The systems therapeutics diagram consists of two rows of four parallel systems components for pharmacologic and pathophysiologic processes, representing the four different levels of interaction between these processes, i.e., at the molecular level, the cellular level, the tissue/organ levels, and finally the clinical level. Where these pivotal interactions occur for individual pharmacologic classes determine the four systems therapeutics categories. These two processes are initiated by an interaction between a pharmacologic agent and a pharmacologic response element on one hand and a hypothetical intrinsic operator and an etiologic causative factor on the other, and then culminate in a therapeutic response. Each of these two processes, pharmacologic and pathophysiologic processes, have their inherent variabilities; this construct further suggests that in addition to pharmacologic processes, pathophysiologic processes also contribute to ultimate patient therapeutic response characteristics.
Ongoing and Future Directions
Progress to-date has focused on generating work on each of the three initial projects, and uploading these to the TRI-institute.org website. Work on the Characteristics of Therapeutic Response project has been hampered by the challenges in identifying appropriate publicly available databases and the best reporting formats. The most recent efforts have focused on the Systems Therapeutics project, including the recently updated diagram, and current and future efforts will include additional work in this area, e.g., examples and exhibits, as well as strengthening collaborative outreach.
