Tag Archives: drug treatment

On Naming Categories

Personal Experience and Observations

Sometimes when you are writing a paper or a report, and you have gotten the main things down – the text and the figures – there is this one issue you need to finalize: the naming of categories included in the paper. Although this is an integral part of the paper, you just don’t consider it as a deciding factor for the acceptance of the work for publication, more like an embellishment. As an example, this could involve work on a categorization of a biomedical system, and you have already decided on the number of categories and their definitions. But what to name the categories?

Writing the Draft with Categories Named by Descriptive Terms

When I was writing the draft of a paper on a categorization of drug treatments based on the relationship between the therapeutic effect of a drug and the pathophysiologic process being treated or prevented (i.e., therapeutic specificity) – this was in 1995 and I was on the faculty at an academic medical center – and after I had completed the text and defined six therapeutic specificity categories, the question arose what their names should be. I recall spending quite some time on what to name the categories, and finally I came up with six descriptive names, adjectives like preventative and symptomatic. Feeling pretty good about the draft, I submitted the manuscript to Clinical Pharmacology & Therapeutics, but the manuscript was rejected and not considered for publication.

Finalizing the Paper with Categories Named by Roman Numerals

I told one of my senior medical school administrators about my experience, and he suggested I talk to a professor at the school who had been an editor of a journal in his discipline for a long time. So I sent him the manuscript for comments, and within a day or two he called me back and told me that in his opinion the paper read and looked fine, but I should not use descriptive names for categories of therapeutic specificity, because reviewers – and readers – will all get hung up on descriptive terms. So, that’s what I did, I just changed the names from descriptive names to numbered items, using Roman numerals (plus “0”), based on the relationship between the therapeutic effect of a drug and the pathophysiologic process(es) being treated or prevented, as follows:

  • Category 0: for disease prevention
  • Category I: directed at disease etiology
  • Category II: directed at specific disease processes
  • Category III: directed at specific disease manifestations
  • Category IV: for non-specific disease manifestations
  • Category V: for non-therapeutic drug use

An astute reader will note that if we don’t consider Categories 0 and V, which involve preventative treatments like vaccines and drugs like anesthetics, respectively, then the publication basically involves four categories of drug treatments for specific diseases. I the submitted the manuscript to the Journal of Clinical Pharmacology, which promptly accepted it, and that’s where was published: A Classification of Drug Action Based on Therapeutic Effects. J. Clin. Pharmacol., 36(8):669-673, 1996 (for therapeutic specificity scheme refer to Figure 2).

There are of course other non-descriptive approaches to naming categories that I could have used, such as numbers or letters, but I settled on Roman numerals as that felt less ordered than plain numbers, these categories being more categorical than hierarchical. In more complicated situations where there might be categories and subcategories, other approaches can be used, such as alphanumeric approaches, and those including lower-case and upper-case letters.

Subsequent Evolution of The Therapeutics Categorization Project

What happened next? More than two decades later – this was in 2018 and I had retired from the pharmaceutical industry – this general therapeutics categorization scheme had evolved into a much more comprehensive description of systems therapeutics, addressing how the pharmacologic and pathophysiologic processes interact, to culminate in a therapeutic response. This is based on a systems therapeutics diagram, which consists of two rows of parallel systems components for pharmacologic and pathophysiologic processes, representing four different biologic levels of interactions between these two processes, i.e., at the molecular, cellular, tissue/organ or the clinical levels, as follows:

  • Category I: at the molecular level, involving elements/factors
  • Category II: at the cellular level, involving mechanisms/pathways
  • Category III: at the tissue/organ level, involving responses/processes
  • Category IV: at the clinical level, involving effects/manifestations

This latter work, Systems Therapeutics: Diagram, Definitions and Illustrative Examples, was posted on the Therapeutics Research Institute’s website (tri-institute.org), in April, 2018 (for systems therapeutics diagram refer to diagram on page 2).

Takeaways

What are the takeaways from this experience? First, when naming categories avoid using descriptive terms, instead use numbers/numerals or letters. Second, regarding the number of categories, observe the parsimony principle, use only as many as are absolutely needed; three would typically be too few, and often four or five will work fine. Third, conceptual projects may often require many iterations and years to evolve as new experience and knowledge has accumulated to inform the work. Fourth, and not the least, seek help and advice from your colleagues and network; the systems therapeutics project might not have happened if the original therapeutic specificity project had not gotten published.

This post has also been published in Medium in August 2020, under the same title.

Great Variability in New Drug Approvals Among Pharmacologic Classes and Therapeutic Classes

Introduction

The objective of the present report is to examine and illustrate the significant variability in new drug approvals among different therapeutic classes, principally by focusing of the number of pharmacologic classes per therapeutic classes, and the number of new drug approvals per therapeutic classes. The data used are from the 2015 Report on the Progression of Modern Therapeutics, available on this website under Reports, which covers 40 therapeutic classes from 14 therapeutic categories, and includes a description of the methodology used.

At the outset, definitions of a few terms used here are in order, as follows:

  • Modern therapeutics – refers to those new drug approvals belonging to a given pharmacologic class that were first approved in the 1970’s to 1980’s timeframe and going forward, as further defined in Progression of Modern Therapeutics (2015 Report).
  • Pharmacologic class – refers typically to a biologic target-based or mechanism of action-related classification, but in some instances involves a chemical classification, or a mix of the two.
  • Therapeutic class – refers to new drug approvals in a given disease or indication, independent of pharmacologic class.
  • Length of registration interest – refers to the time interval between the dates of the first and the latest new drug approval within a given pharmacologic class.

Number of Pharmacologic Classes per Therapeutic Classes

The number of pharmacologic classes per therapeutic classes is shown in the graph below, in a descending order, for 38 of the 40 therapeutic classes covered in the Progression of Modern Therapeutics (2015 Report). For the purposes of the present analyses, the following two therapeutic classes were not included, i.e., Pediatric Acute Lymphoblastic Leukemia and Malaria, since these contained a significant proportion of older drugs. 

Click here for a larger graph. Note the wide range 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. The mean and median values were 4.3 and 4, respectively.

Modern Therapeutics New Drug Approvals per Therapeutic Classes

Below are shown the total number of new drug approvals for 38 of the 40 therapeutic classes covered in the Progression of Modern Therapeutics (2015 Report). Click here for a larger graph. Note the 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. The mean and median values were 11.5 and 9.5, respectively.

Summary Data

Below is summary data used in the two graphs above, specifically, the number of pharmacologic classes per therapeutic classes, along with the range of new drug approvals for those pharmacologic classes, the total number of new drug approvals for that therapeutic class, and the mean and median length of registration interest in the pharmacologic classes within each therapeutic class (counted in decimal years). Pharmacologic classes with only 1 new drug approval and those with <1 year of length of registration interest are not included; the number of pharmacologic classes averaged for each therapeutic class is shown in parenthesis. The data is from the 2015 Report.

Cardiovascular Therapeutics

  • Hypertension: 6 pharmacologic classes, with 1 to 14 new drug approvals each, totaling 44, with mean and median length of registration interest of 19.5 and 15.1 decimal years, respectively (N=5).
  • Dyslipidemia: 7 pharmacologic classes, with 1 to 8 new drug approvals each, totaling 19, with mean and median length of registration interest of 25.1 and 26.7 decimal years, respectively (N=3).

Hematologic Therapeutics

  • Thrombosis: 4 pharmacologic classes, with 1 to 5 new drug approvals each, totaling 14, with mean and median length of registration interest of 10.9 and 8.7 decimal years, respectively (N=3).
  • Thrombolysis: 3 pharmacologic classes, with 1 to 3 new drug approvals each, totaling 6, with mean and median length of registration interest of 12.3 and 12.3 decimal years, respectively (N=2).
  • Idiopathic Thrombocytopenic Purpura: 1 pharmacologic class, with 2 new drug approvals, totaling 2, length of registration interest not calculated.

Gastroenterologic Therapeutics

  • Acid Reflux & Ulcer Disease: 3 pharmacologic classes, with 2 to 5 new drug approvals each, totaling 11, with mean and median length of registration interest of 9.7 and 10.7 decimal years, respectively (N=3).
  • Inflammatory Bowel Diseases: 2 pharmacologic classes, with 2 and 4 new drug approvals each, totaling 6, with mean and median length of registration interest of 10.5 and 10.5 decimal years, respectively (N=2).
  • Irritable Bowel Syndrome: 6 pharmacologic classes, with 1 new drug approval each, totaling 6, length of registration interest not calculated.
  • Prevention of Nauseas & Vomiting Associated with Cancer Chemotherapy: 2 pharmacologic classes, with 3 and 4 new drug approvals each, totaling 7, with mean and median length of registration interest of 12.5 and 12.5 decimal years, respectively (N=2).

Pulmonary Therapeutics

  • Asthma: 7 pharmacologic classes, with 1 to 6 new drug approvals each, totaling 18, with mean and median length of registration interest of 18.1 and 19.8 decimal years, respectively (N=4).
  • Chronic Obstructive Pulmonary Disease: 3 pharmacologic classes, with 1 to 9 new drug approvals each, totaling 14, with mean and median length of registration interest of 30.1 and 30.1 decimal years, respectively (N=2).
  • Pulmonary Arterial Hypertension: 4 pharmacologic classes, with 1 to 4 new drug approvals each, totaling 10, with mean and median length of registration interest of 12.0 and 11.8 decimal years, respectively (N=3).
  • Idiopathic Pulmonary Fibrosis: 2 pharmacologic classes, with 1 new drug approval each, totaling 2, length of registration interest not calculated.
  • Cystic Fibrosis: 3 pharmacologic classes, with 1 to 3 new drug approvals each, totaling 6, with length of registration interest of 3.4 decimal years (N=1).

Endocrinologic Therapeutics

  • Type-2 Diabetes: 11 pharmacologic classes, with 1 to 5 new drug approvals each, totaling 27, with mean and median length of registration interest of 8.7 and 3.0 decimal years, respectively (N=7).
  • Obesity: 7 pharmacologic classes, with 1 new drug approval each, totaling 7, length of registration interest not calculated.
  • Osteoporosis: 5 pharmacologic classes, with 1 to 4 new drug approvals each, totaling 9, with mean and median length of registration interest of 14.3 and 14.3 decimal years, respectively (N=2).

Psychopharmacologic Therapeutics

  • Depression: 4 pharmacologic classes, with 3 to 8 new drug approvals each, totaling 22, with mean and median length of registration interest of 18.7 and 19.6 decimal years, respectively (N=4).
  • Schizophrenia: 2 pharmacologic classes, with 11 and 12 new drug approvals each, totaling 23, with mean and median length of registration interest of 26.4 and 26.4 decimal years, respectively (N=2).
  • Attention Deficit Hyperactivity Disorder: 4 pharmacologic classes, with 1 to 2 new drug approvals each, totaling 7, length of registration interest not calculated. Note enantiomers and prodrugs are not included.
  • Insomnia: 5 pharmacologic classes, with 1 to 5 new drug approvals each, totaling 11, with mean and median length of registration interest of 16.3 and 16.3 decimal years, respectively (N=2).

Neurologic Therapeutics

  • Alzheimer’s Disease: 2 pharmacologic classes, with 1 and 4 new drug approvals each, totaling 5, with length of registration interest of 7.4 decimal years (N=1).
  • Parkinson’s Disease: 5 pharmacologic classes, with 1 to 6 new drug approvals each, totaling 14, with mean and median length of registration interest of 9.6 and 8.5 decimal years, respectively (N=4).
  • Multiple Sclerosis: 9 pharmacologic classes, with 1 to 5 new drug approvals each, totaling 13, with length of registration interest of 21.1 decimal years (N=1).
  • Migraine: 5 pharmacologic classes, with 1 to 7 new drug approvals each, totaling 15, with mean and median length of registration interest of 9 decimal years, respectively (N=2). Note values for two pharmacologic classes not readily available, and thus not included.

Rheumatologic Therapeutics

  • Rheumatoid Arthritis: 8 pharmacologic classes, with 1 to 5 new drug approvals each, totaling 13, with mean and median length of registration interest of 9.3 and 9.3 decimal years, respectively (N=2).
  • Systemic Lupus Erythematosus: 1 pharmacologic classes, with 1 new drug approval, totaling 1, length of registration not calculated.
  • Gout and Hyperuricemia: 3 pharmacologic classes, with 1 to 3 new drug approvals each, totaling 6, with mean and median length of registration interest of 53.5 and 53.5 decimal years, respectively (N=2).
  • Fibromyalgia: 2 pharmacologic classes, with 1 and 2 new drug approvals each, totaling 3, length of registration interest not calculated.

Genitourinary Therapeutics

  • Urinary Incontinence: 3 pharmacologic classes, with 1 to 6 new drug approvals each, totaling 8, with length of registration interest of 33.6 decimal years (N=1).
  • Erectile Dysfunction: 2 pharmacologic classes, with 1 and 4 new drug approvals each, totaling 5, with length of registration interest of 14.1 decimal years (N=1).
  • Benign Prostatic Hyperplasia: 3 pharmacologic classes, with 1 to 4 new drug approvals each, totaling 7, with mean and median length of registration interest of 15.3 and 15.3, decimal years, respectively (N=2).

Dermatologic Therapeutics

  • Plaque Psoriasis: 5 pharmacologic classes, with 1 to 3 new drug approvals each, totaling 7, with length of registration interest of 3.7 decimal years (N=1).

Ophthalmologic Therapeutics

  • Glaucoma: 4 pharmacologic classes, with 2 to 5 new drug approvals each, totaling 14, with mean and median length of registration interest of 11.9 and 13.9 decimal years, respectively (N=4).
  • Age-related Macular Degeneration: 2 pharmacologic classes, with 1 and 3 new drug approvals each, totaling 4, with length of registration interest of 6.9 decimal years (N=1).

Antiviral Therapeutics

  • HIV-1/AIDS: 6 pharmacologic classes, with 1 to 10 new drug approvals each, totaling 28, with mean and median length of registration interest of 10.7 and 11.1 decimal years, respectively (N=4).
  • Hepatitis C: 5 pharmacologic classes, with 1 to 4 new drug approvals each, totaling 13, with mean and median length of registration interest of 4.8 and 2.1 decimal years, respectively (N=4).

Oncologic Therapeutics

  • Melanoma: 8 pharmacologic classes, with 1 to 2 new drug approvals each, totaling 11, with mean and median length of registration interest of 2.1 and 2.1 decimal years, respectively (N=2).

Comments

A few high-level comments are listed below:

Pharmacologic ClassesNote the wide variability in the number of pharmacologic classes per therapeutic classes, ranging from 11 and 9 for Type-2 Diabetes and Multiple Sclerosis, respectively, and 8 each for Rheumatoid Arthritis and Melanoma, to 1 each for Idiopathic Thrombocytopenic Purpura and Systemic Lupus Erythematosus, and several therapeutic classes with 2 each, including Alzheimer’s Disease and Schizophrenia. Note that the mean and median for pharmacologic classes per therapeutic classes (N=38) are 4.3 and 4, respectively.

Therapeutic Classes – Note the wide variability in the total number of new drug approvals for the different therapeutic classes, ranging from 44 for Hypertension, 28 for HIV-1/AIDS, 27 for Type-2 Diabetes and 23 for Schizophrenia, to 1 for Systemic Lupus Erythematosus, 2 each for Idiopathic Thrombocytopenic Purpura and Idiopathic Pulmonary Fibrosis (both orphan indications) and 3 for Fibromyalgia. Note that the mean and median for total number of new drug approvals per therapeutic class (N=38) are 11.5 and 9.5, respectively.

Speculations – It is tempting to speculate what might be the reasons underlying such wide variabilities in the number of pharmacologic classes per therapeutic classes as well as in the total number of new drug approvals per therapeutic classes, but that will be left to another time. Public discussion on this important topic, however, is very important, since at a high level, these are likely to relate to how society attempts to address varying degrees of scientific knowledge about disease etiology and pathophysiology, levels of research funding, commercial assessment, and different levels of unmet medical need. 

Length of Registration Interest – The length of registration interest across the different therapeutic classes (based on those with >2 pharmacologic classes) varied greatly, with median values higher than 20 decimal years for Schizophrenia (26.4), Dyslipidemia (26.7), Chronic Obstructive Pulmonary Disease (30.1) and Gout and Hyperuricemia (53.5). This parameter is of interest since sometimes it can be an indication of a need for better treatment and new biologic targets.

Classifications – It is noted that the pharmacologic classifications for modern therapeutics typically involve biologic target-based or mechanism of action-related classifications, but in some instances these involve chemical classifications, e.g., for Malaria and Pediatric Acute Lymphoblastic Leukemia (both of which were not included in the present analyses), or a mix of the two, e.g., for Migraine and Attention Deficit Hyperactivity Disorder. Going forward, it is desirable to have uniform biologically based approaches for pharmacologic classifications. 

Modern Therapeutics vs. Older Drugs – The project on Progression of Modern Therapeutics, as the name implies, addresses modern therapeutic, as defined above. Thus, it is recognized that older drugs, typically those introduced before the 1970’s, which are not included in this project although still in active clinical use, could  influence the key parameters under study if included in these analyses, i.e., the number of pharmacologic classes per therapeutic classes, and the total number of drug approvals per therapeutic classes. 

Conclusion

The present assessment of modern therapeutics has illustrated wide variability in the number of pharmacologic classes per 38 therapeutic classes. These ranged from 11 for Type-2 Diabetes to 1 for Systemic Lupus Erythematosus, with a median of 4. Similar wide variability was also evident for the number of new drug approvals for each of these 38 therapeutic classes. These ranged from 44 for Hypertension to 1 for Systemic Lupus Erythematosus, with a median of 9.5.

It is noted that although the separation between older drugs and modern therapeutics is somewhat arbitrary, over these past four decades or so there have been impressive advances in new drug introductions, including numerous new pharmacologic classes that have changed and are changing the treatment and outcome of a number of diseases, e.g., Hypertension, Dyslipidemia, Acid Reflux and Ulcer Disease, Inflammatory Bowel Diseases, Type-2 Diabetes, Multiple Sclerosis, Rheumatoid Arthritis, Melanoma, Hepatitis C and HIV-1/AIDS, to name just a few. It is also noted that to date the project on the Progression of Modern Therapeutics has only covered two Oncologic Therapeutics diseases, i.e., Melanoma and Pediatric Acute Lymphoblastic Leukemia, but this particular therapeutic category has witnessed significant progress over the past few decades. Therefore, considering these recent therapeutic advances across a great number of diseases one can only remain highly optimistic about the future of drug discovery and development, and the introduction of novel new drugs.