Hello to all potential stakeholders of this network and question to discuss

Starting from basic knowledge of clinical pharmacology and applied mathematics or biostatistics, the elements to consider are some of the following:

• If Clinical Trials are the gold standard to compare the results in the research of efficacy and safety of new drugs.
• When choosing Clinical Trials as the standard of comparison, take into account the alpha and beta values ​​to decide the critical point of statistical and clinical significance of the results obtained.
• The contrast that is made of the results obtained with the objectives, hypotheses and justification of the research.
• The size of the samples in a meta-analysis, if large and small samples are compared indistinctly and if the sizes, although different, are significant in the universe where they come from.

regards

José Luis

Dear George Stoica

Agree

Hello everyone

Recapitulating about the total process in the manufacture of new drugs (which usually involves the discovery of new molecules and the procedure for their transformation into drugs) is laborious and generally time consuming.

Before and not long ago, an investment of billions of pesos was required and an approximate time between the design of the molecule, the manufacture of the drug and the phases of pharmacological research of efficacy and safety for its authorization and use in humans Phases : I, II and III) and pharmacovigilance (FIV) of effectiveness in the field of reality.

In each of these parts of the process, which involves various academic, research, computer and design and biostatistics procedures, all of the above must be considered:

• Economic-Financial,
• Design and synthesis of the new molecule,
• Transformation of the new molecule into potential medicine,
• Theoretical experiments and computer simulations with specific artificial intelligence programs for the chemical or biochemical design of the potential medicine,
• Laboratory synthesis of the molecule and
• Finally pharmacological investigation of efficacy, safety and effectiveness.

regards

José Luis

In addition to my previous note, I have to confirm information already mentioned and answering a frequently asked question:

Are the phases of pharmacological research on the efficacy and safety of drugs the same for vaccines?

• If they are formally three phases, which has been mentioned frequently with the manufacture of the anticovid-19 vaccines; phase III is in which the efficacy and safety of the drug or vaccine in question is properly investigated, in clinical trials with a statistically determined sample of sufficient size for the results obtained to be significant.
• Once phase III is finished, both in drugs and vaccines, the product (vaccine or drug) is submitted to evaluation by technology regulatory agencies (drugs, new molecules); FDA in the United States; EMEA in Western Europe, COFEPRIS in Mexico; and the regulatory agency for specific drugs (vaccines) in each country.
• Once its use in humans and sale to the public has been authorized (with a prescription with a prescription), phase IV begins, called Pharmacovigilance in Medicines and Evaluation of Transient Undesirable Events Related to Vaccination (ETAV in Mexico), to decide on a change in the formulation of the new molecule, drug or vaccine; or eventually, remove it from the marking for human use.

regards

José Luis

The clinical trial process is usually very long (to be counted in several years); gaining the statistical power of medical evidence is delayed in 80% of all phases (0-4), because of the usual lack of volunteers.

Dear Stephen I. Ternyik

It is true that the pharmacological research process is very long to complete all the phases, at least 3 to use the drugs in humans to obtain an Effective and Safe product; but it is the only one that tells us that the drug to be prescribed in humans will have more benefits than risks.

As phase III of the Clinical Trial is carried out in the case of vaccines in healthy volunteers, it is essential not to ignore Phase IV of Pharmacovigilance, which will provide us with information not on efficacy but on effectiveness.

regards

José Luis

Hello everybody

More than a year after the COVID-19 pandemic was declared, we already have more experience in the epidemiological management of it, including prevention and protection measures for the different populations of the world; which has resulted in a great revolution in culture, beliefs of all kinds and religion.

In the field of science and technology, it has resulted in a great advance in telecommunications and social networks, in biotechnology, in computational computing thanks to the development and innovations in deep learning artificial intelligence (IAap); and finally, the application of all this to improve people's quality of life and to find, for the time being, some useful drugs for the etiopathogenic treatment of SARS-CoV-2 infection.

Unpublished facts so far, is the manufacture of several anticovid-19 vaccines, which are available to everyone, with more or less access depending on the speed of manufacture, transportation and financial funds to meet the expenses that all this implies . Also a single specific antiviral authorized by the US FDA (Remdesivir).

In biotechnology and genetic manipulation, it has been possible to know the "genetic map" of SARS-CoV-2, which together with IAap, made it possible to analyze and synthesize a large amount of information to know the mechanism of attack and entry of the virus to human cells (pneumocytes, for example); in such a way that we now know more about the "spike or spike" viral antigen with its molecular antigenic constitution and the way the virus reproduces, the basis for the development of mRNA vaccines (other vaccines were made based on previous technology that was developed to make the influenza vaccine using part of the inactivated virus as a vehicle).

Almost half a year after these discoveries and the application of the first doses of the vaccines to the general population, unknown adverse reactions have been identified in the 3 phases of pharmacological investigation of Efficacy and Safety (I-III) and that can only be identified in the follow-up phase (phase IV) or pharmacovigilance; In other words, the data we are obtaining on adverse reactions in the general population are "Effectiveness and Safety".

Useful information for the immediate future, to adjust the knowledge we have of the specific adverse reactions of the anticovid-19 vaccines, in order to prevent them, adjust their application as required in different age and risk groups, and where appropriate , prescription of prophylactic treatments. All while waiting to have more specific antivirals with easy access and cost and to overcome this pandemic with better physical and emotional health.

Continuing in the same speech, I comment on part of some reflections related to new knowledge and technological innovation:

There is no doubt about the theoretical-practical relationship that exists between theoretical scientific knowledge and the generation of technology.

The vision from micro to nano in some disciplinary fields, gains in depth, but loses in extension.

The positive and reductionist scientific gaze gains in measurable objectivity, but loses subjectivity and quality (quality).

Technological innovation does not always incorporate new theoretical knowledge, it only improves existing technology, a product of practice, in some sense.

The positive and reductionist look reduces uncertainty to a certain extent, but it does not always have immediate practical application for the benefit of society.

The generation of all kinds of scientific knowledge (derived from different disciplinary fields), are not always linked to each other and much less to the whole of the social and human ecosystem.

New scientific knowledge can be generated, starting from findings or identifying links between different disciplines, thus creating new fields of knowledge;

Examples of union of disciplines that have been united: case of general biology, microbiology, molecular biology, genetics and biochemistry; when their strategies, methods and procedures are brought together and harmoniously combined to give rise to the new science, Biotechnology.

A similar situation occurs with the social and humanistic disciplines that are based on scientific evidence; case: Sociology, demography, anthropology, economics, health, education, etc.

Example of new social and humanistic disciplines that, when linked, create new fields of human doing and knowledge: Pedagogy, childcare and education, with educational sciences; Psychology, Literature, History, Art and Medicine, with Psychiatry and Psychoanalysis; Clinical medicine with molecular biology, physicochemical, biochemical and genetic, with Scientific Medicine or biomedical model of clinical medicine.

In this way, with method and systemic vision; We will be able to link all the scientific disciplines that have been technologically developed, but are currently unrelated, leading men and women to disciplinary scholarship, but also to ignorance of the comprehensible and interpretable knowledge of the biophysical, human, social world and itself, to planetary science or the advent of Gaia.

Hi all

Until the time of the COVID-19 pandemic, there is no longer any doubt that clinical pharmacology applied to anticovid vaccines continues to be the gold standard for their development; in such a way that before they have been applied to the general population, they have already passed through the filter of the 3 stages of pharmacological research, including the one prior to their commercialization, which is the Clinical Trials of Efficacy and Safety.

Given this aforementioned antecedent, I put at your disposal the following observations and considerations:

• During the post-marketing or phase IV observation period (pharmacovigilance and events temporarily associated with vaccination), Effectiveness is being evaluated in practice.
• In all these phases of research and biomedical and clinical monitoring of the effects of the different authorized vaccines, in the analysis of the information, the strength of the evidence remains objective with the mathematical handling of the data using biostatistics.
• Now and before the avalanche of information available from different participating scientific disciplines, the management of information using large databases already structured and the development of computer programs (Big-Data) based on deep learning artificial intelligence is mandatory. AIdl); In order to filter and select the input information (variables) and codes and algorithms to associate the processed information and extract it as already integrated results, forming indices and indicators.
• As can be seen, AIdl takes a preponderant place both in the design of information for the manufacture of vaccines and antiviral drugs and in the statistical handling of a large amount of information derived from different disciplinary fields.