Good Clinical Practices
(Part-1)

Dr. K. H. H. V. S. S. Narasimha Murthy
Professor, Department of Kayachikitsa,
Faculty of Ayurveda, IMS, BHU, Varanasi

based on the lecture available at-“Good Clinical Practice “

Basic concepts related to clinical practice-
Before going to discuss the good clinical practices, some basic concepts which are related to these clinical practices such as Ayu have been discussed here. Ayu is defined in shloka given below

शरीरेन्द्रियसत्त्वात्मसंयोगो धारि जीवितम्|
नित्यगश्चानुबन्धश्च पर्यायैरायुरुच्यते||
(Ch.Su.1/42)

Ayu (life) is defined as the combination of Sharira (body), Indriya (sense organs) mind and soul. Sharira composed of Dosha, Dhatu and Mala all together which is considered as the physical body. The second component of the Ayu is Indriya that is Pancha Jnana Indriyas what we have. Here Indriyas are mainly considered Jnana Indriya. It does not mean that only Jnana Indriyas, it also includes the Karma Indriyas. Sattva means mind and Atma is the soul. So, the combination of these four that is Sharira, Indriya, Sattva and Atma in a circular bounding fashion and interrelated fashion is considered as Ayu. So, this is the Ayu which is the main motto of the Ayurveda that is ‘Ayuhu Vindati Ayurveda’, so where we learn about the techniques that which can keep the Ayu in a good manner.

Clinical Practice:

The clinical practice means is nothing but Chikitsa that is doing treatment. Treatment is the considered as that the therapeutics. Therefore, consist of the measures or operations by way of which concordance of the tissue elements can be sustained and this achieving the concordance of the tissue elements constitute the duly duty of the physician.

याभिः क्रियाभिर्जायन्ते शरीरे धातवः समाः|
सा चिकित्सा विकाराणां कर्म तद्भिषजां स्मृतम्||
(Ch.Su.16/34)

It means the technology or methodology that can bring back the normalcy of the Dhatus, i.e., Sharir Dhatu (body tissues). Sharira dhatu includes Vata, Pitta, and Kapha. So, bringing back the normalcy, by whatever means, is considered as Chikitsa (treatment). Chikitsa also consists of four Padas (pillars) for conducting the treatment, namely Bhisak (physician), Dravya (drug), Upasthata, and Rogi. These are the Pada Chatushatya. In this, the physician, the drug, and Upasthata, engaging with the patient to restore normalcy, represent the essence of treatment.

चतुर्णां भिषगादीनां शस्तानां धातुवैकृते|
प्रवृत्तिर्धातुसाम्यार्था चिकित्सेत्यभिधीयते||
(Ch.Su.9/5)

 The disequilibrium state of Dosha has to be brought into the equilibrium state, meaning that using these Chikitsa Pada is called treatment. A particular treatment has different synonyms, e.g., Chikitsitam, Vyadiharam, Pathyam, Sadhanam, Aoushadham, Prayaschittam, Prashamanam, Prakruti sthapanam, and Hitam.”

चिकित्सितं व्याधिहरं पथ्यं साधनमौषधम्|
प्रायश्चित्तं प्रशमनं प्रकृतिस्थापनं हितम्||
( Ch. Chi 1/1 / 3)

These are different synonyms considered for Chikitsa, Vyadihara, Pathya, Sadhana, and Aoushada. Here, Aoushada holds significant importance. Aoushada refers to drugs, not just any drug, but those prepared using herbs and minerals. Prayaschitta, Prasamana, Prakruti-sthapana, are all synonyms for therapeutics. The drugs we use possess certain qualities. Some pacify the Doshas, some vitiate the Dhatus, and some are used for maintaining normal health.

यथा विषं यथा शस्त्रं यथाऽग्निरशनिर्यथा|
तथौषधमविज्ञातं विज्ञातममृतं यथा||१२४||
(Ch.Su1/124)

These are three different methods that we have here. If a particular drug is not used properly, it can act like Visha (poison), a weapon (Shastra), or a bolt of thunder (Agni). If the drug is used properly, it becomes nectar. If it is not used in the proper method or manner, it is considered as Visha (poison), Shastra (weapon), Agni (fire), or even a thunderbolt. The drug, when perfectly understood, can be used for treatment, becoming ambrosia, which is nectar. If not, it can harm and even kill a person. Therefore, it cannot be administered merely by knowing the name of the drug or its properties. It needs to be understood thoroughly, comprehended properly, and administered correctly for the treatment to be effective.

तदेव युक्तं भैषज्यं यदारोग्याय कल्पते|
स चैव भिषजां श्रेष्ठो रोगेभ्यो यः प्रमोचयेत्||
(Ch.Su1/134)

That’s what we must consider. So, any treatment or drug given in the proper way can restore normalcy and maintain health, which is Arogya. This means that the physician, one of the major pillars of the treatment, must fully understand the drugs. They should possess knowledge of the right medicine, and the physician must be involved in a good methodology to treat the patients. Therefore, when the patient, physician, and the right medicine come together, it can result in a successful clinical practice.

 What is a good clinical practice?

A good clinical practice is an international, ethical, scientific quality standard for designing, conducting, recording, and reporting trials involving human subjects. Previously, such guidelines were not in place. These guidelines were developed due to certain phenomena that occurred in our history. Compliance with these standards provides public assurance that the rights, safety, and well-being of trial subjects are protected, consistent with the principles outlined in the Declaration of Helsinki. This declaration serves as the foundation for good clinical practices. It is important to understand what it entails and why it came into existence.

There are several declarations that we can refer to, such as the one made by the World Medical Association (WMA) in Helsinki. They declared ethical principles for medical research involving human subjects. In the past, there were no established ethical codes or principles to follow when human subjects were involved. The World Medical Association’s Declaration of Helsinki was adopted during the 18th World Medical Association General Assembly, held in 1964. Subsequent meetings took place in Tokyo, Japan in 1975, Venice, Italy in 1983, Hong Kong in 1989, and so on, as mentioned below.

WMA Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects

• Adopted by the 18th WMA (World Medical Association) General Assembly, Helsinki, Finland, June 1964 and amended by the:

• 29th WMA General Assembly, Tokyo, Japan, October 1975

• 35th WMA General Assembly, Venice, Italy, October 1983

• 41st WMA General Assembly, Hong Kong, September 1989

• 48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996

• 52nd WMA General Assembly, Edinburgh, Scotland, October 2000

• 53rd WMA General Assembly, Washington DC, USA, October 2002 (Note of Clarification added)

• 55th WMA General Assembly, Tokyo, Japan, October 2004 (Note of Clarification added)

• 59th WMA General Assembly, Seoul, Republic of Korea, October 2008

• 64th WMA General Assembly, Fortaleza, Brazil, October 2013

https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research- involving-human-subjects/

The objectives of this declaration

The International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) and the Good Clinical Practice (GCP) guidelines aim to establish a unified standard for the European Union, Japan, and the United States. This standardization facilitates the mutual acceptance of clinical data by regulatory authorities in these jurisdictions. Without these guidelines, practices and research conducted in one region may not be accepted in others due to the absence of proper standards. For instance, if the Japanese research does not adhere to good clinical practices, it may not be accepted by other countries. The same applies to the European Union and the United States. Therefore, good clinical practice plays a vital role in ensuring acceptance and reliability of research findings across different regions.

 Why we need the guidelines? What is the real need of regulations?

There have been several violations of human rights throughout history. For example, the Nazi war crimes, Tuskegee syphilis trial, Thalidomide disaster, Jews chronic disease trial, Willowbrook study, and Milgram study all serve as examples of such violations. In the case of Nazi medical war crimes during World War II, Nazi physicians conducted unprecedented experiments on captured humans, who became prisoners of war. These experiments inflicted immense harm and suffering on the subjects, surpassing any acceptable limits for medical experiments. The outcomes often led to death, disfigurement, or permanent disability, making them examples of medical torture. While losing a limb or life in war is a separate issue, when individuals are subjected to drugs, treatments, or medical experiments that result in the loss of body parts or even death, it represents a grave violation of human rights and constitutes medical torture.

Medical experiments were performed on thousands of prisoners in concentration camps, involving deadly studies and acts of torture. For instance, prisoners were injected with gasoline and live viruses, submerged in ice-cold water for hours to study hypothermia and its effects on the body, forced to ingest poisons for toxicological studies, and purposely infected with bacteria, dirt, and silver of glass through incisions made by medical personnel. While these experiments were conducted to study medical components, they were inherently unethical and inhumane.

Victim of the tuberculosis and medical experiment, during the time when tuberculosis was a highly spreading disease, various experiments were conducted without proper treatment methods. For example, prisoners were subjected to experiments in compression chambers to understand the effects of pressure on the body. These experiments aimed to determine how aircraft crews could survive without oxygen at high altitudes. To gather such information, prisoners were placed in pressurized chambers. Additionally, there were experiments involving immersing people in ice water. In the study aimed at preventing and understanding hypothermia and its treatment, around 280 to 300 victims were selected as subjects. These individuals were subjected to experiments, including enduring a tank of ice water for more than five hours. This tragic and unacceptable experiment caused immense harm.

Similarly, there were trials conducted on doctors. In 1946, an American military tribunal initiated criminal proceedings against 23 prominent German physicians who were associated with the Nazi regime. Out of the 23, 16 doctors were found guilty of engaging in unethical medical experimentation. Seven of them were sentenced to death. These events led to the development of the Nuremberg Code, which established ethical standards for medical research.

Another infamous study is the Tuskegee syphilis study, which aimed to examine the natural progression of untreated syphilis. During the 1940s and 50s, tuberculosis and syphilis were two major diseases. In India, syphilis was introduced by the French and was referred to as “Firanga Roga” in Ayurveda. The disease brought along with it the use of drugs like Chopchini. Subsequently, Rasa Shastra experts developed various medications, including Rasakarpura, for treating syphilis. However, in the Tuskegee syphilis study, long-term research was conducted on African-American males as research participants.

The Tuskegee syphilis study took place in Tuskegee, Alabama and was conducted by the United States Public Health Service between the 1930s and 1970. In this study, over 400 African-American men with syphilis were recruited without their informed consent. The patients were not given any information about the study and were actually misinformed that they were receiving special free treatment. This misinformation was used to conduct procedures such as spinal taps without their knowledge or consent. In the 1940s, Penicillin was introduced as an effective treatment for syphilis. However, the study continued without providing the patients with any treatment. They were neither informed nor given antibiotics or any other medication. Instead, the study aimed to observe the progression of untreated syphilis and its effects on the body. The first accounts of this study appeared in national papers in 1972, and it led to the development of the Belmont report in 1978. The Belmont report established ethical principles and guidelines for the protection of human subjects in research.