Medicinal Plants In Health Management

The struggle of a man against disease and death is as old as the history itself. On the basis of skill, knowledge and practices based on the theories, beliefs & experiences indigenous all civilizations has developed their own treatment system which is now called as traditional treatment system. The base of almost all such treatment system is plants. Various as scholar and medical men, since the vedic period dawn to the present century, have contributed a lot on the use of medicinal plants in health care.

Plants are the most ancient source of drugs and the plant based medicaments, the countrymen’s prime therapeutic weapon, are still is front line today for treating a large number of diseases. According to Professor N.R. Fransworth the plants are “The sleeping giants of drug development today and will represent in future as first class source for new medicaments.

The most established traditional system is Ayurveda. The objectives of Ayurveda are Dhatu Samya, Swastha Vritta and Atura Vritta. Proper cure of a disease entirely depends upon rational interaction of four limbs of therapies or chikitsa chatushpada and drug is one of the components of therapy. The material Media of Ayurveda is very vast. It comprises of Plants, animals and metals and aquatic products but plant drugs occupy a large area for the prevention and promotion of health and treatment of Disease.

It may be noted that Ayurveda (sanskrit Ayur : life, Veda : science, Knowledge) is the ancient Indian system of health management which is still widely practiced in the sense of “holistic’ approach, especially for metabolic disorders. Ayurvedic medicines are mostly based on plant materials. The entire mountainous region of the country is considered a vast repository of medicinal herbs. It has been estimated that the sources of 80% Ayurvedic medicines are found in the western Himalayas.

A medicinal plant is any plant which is one or more of its organs substances that can be used for therapeutic purposes or which are precursors for chemo pharmaceutical semi-synthesis. The definition makes it possible to distinguish between the medicinal plants that are already known whose therapeutic character or a precursor of certain molecular have been established scientifically and the other plants which are regarded as medicinal but have not yet been subjected to thorough scientific study. Researches for the identification, development and utilization of plants should be given high priority for the development of Indigenous system of health care in order to reduce drug bills and develop more acceptable and more readily acceptable to the people and with better coverage.

The following are the some of the examples of plants which are used in primary health care extensively specially in the Rural Area:

1	Tulsi	Ocimum sanctum	Promotes immunity
2	Bhallatak	Semicarpus anacardium	Anti-cancer agent
3	Ashwagandha	Wiothania somnifera	General nervine tonic
4	Amalaki	Emblica officinals	Rejuvenate (resayana)
5	Manookharni (Brahmi)	Hydsrocotyl ariatica	Improves memory and intelligence
6	Shankhapushpi	Convulvulus pluricalis	Improves memory and intelligence
7	Vacha	Acorus colamus	Improves speech in children
8	Jyolishmati	Collesterus pariniculala	Improves mental health
9	Arguna	Terminalia Arjuna	Most effective cardio tonic
10	Shirish	Albebia lebeck	Anti-asthma
11	Haridra	Curcuma longum	Anti-Allergic
12	Katuki	Picrorrhiza Kurroa	Jaundiced Hepatitis
13	Punarnawa	Boerhavia diffusa	Kidney disorders
14	Varuna	Gitavia deligiosa	Bladder disorders
15	Kapikachu	Mucona Pruriens	Impotency
16	Shatavari	Asparagus racimosus	Galactogogue
17	Bala	Sida cardifolia	Baby tonic
18	Japakusum	Haviscus Rosa cyanosus	Antifertility agent
19	Vijaysar	Ptericorpus Marsupium	Ant diabetic
20	Kutaj	Holerene Antidysenterica	Colitis

Some of the drugs which have come to light in our experience to have significant action and the observation have been also supported. Scientific observations are as follows

Psychotropic drugs : A group of drugs which have been observed as medhya drugs and few others have shown to have definite action on brain called as psychotropic drugs e.g.

• Shankhapushupi      -           Convolvulus Pluricaulis choisy
• Mandukharmi           -           Centella Asiatica
• Brahmi                      -           Bacopa – monnieri
• Ashwagandha          -           Withania somnifera Dunal
• Vacha                        -           Acorus calamus
• Jyotismati                  -           Calastrus paniculatus
• Jatamansi                  -           Nordostachys Jatamansi

The drugs have a true tranquilizing effect on brain without inducing any hangover or dullness of brain. These are helpful in inducing sleep and freshness of brain for better performance, thus improving the intellectual activity and memory also. These plants also help as to come out of severe complexes, depression and antisocial trends e.g. suicide, hemisuidal, homicidal etc.

By their virtue of having effect on psychic they are also effective for the management several psychosomatic disorders. Heart disease, hypertensions peptic ulcer, ulcerative colitis are some of the notable disease of this group. These drugs have also anabolic effect on general metabolism. Cardio vascular drugs: cardio vascular disease is a great cause of mortality like cancer in the western countries. But the developing countries are no more exception. The incidence of high B.P., heart disease, and obesity is in increasing in China and India. Usually the people have a feeling that it is disease of affluent society and the treatment as only possible by the modern drugs. But none of them is true; there is description of this disease in Ayurvedic literature which is referred to be a contribution of 500 B.C. The treatment of heart disease is still in practice in Indian system of medicine. The effective drugs of cardiovascular system are as follows:

Arjun                          :Teminalia Arjuna

Gugulu                       : Balsamodendron mukul

Pushkarmula             : Inulr Recemosus

Shalpharmi                : Desmodium gangetiun

Karbir                         : Theretia Nereifolia

Kutha                          : Holerrbena – Antidysenterica

Rasona                       : Alliun – Sativum 

Thus a good number of cardio vascular drugs are in our urmamentorium of medicinal plants which can be developed as potent drugs in future.

Respiratory System:

According to Ayurveda respiratory system is the chief site of Kapha hence the disease also produce the symptoms of Kakha. Vata is also involved simultaneously in some disease as Bonchial Asthma. It is a well-known fact that if is a disease having ofstruction branch opathy. Obstruction may be because of the Oedoma/ inflammation of the mucosa or due to bronco – construction, forma is allergic inflammation due to excess of histamine like substances and the latter is because of the predominance of anticholenergic substance. Allergic manifestatias may produce several symptoms of respiratory tract disorder e.g. Allergic Rhinitis, Nasopharongitis Brynchitis etc. The following drugs have been found to be useful for amelioration of the above pathology.

Tulsi                   :Olimum sanctum

Sirisha               :Albizzia Leffeck benth

Kantkari             :Solan um xanthocarpum

Vasa                   :Adhatoda Vasca

Madhuyasti        :Curucuma Longa

Sunthi                 :Zingiber Feivale

Bibhitaka           :Terminalia Belerica

Tulsi is supposed to be most pious plant in Indian culture. No worship is complete without offering the tender leaves to God and then same is distributed among the masses for beneficial effect on health. The evidences are in favour that it is an immunostimulant thus providing increased general resistance for the prevention of disease. It is antipyretic, antinflamatery, expectorant and milid bronchodiloty thus of great help to the patient of upper respiratory and bronchial disease. Sirisha is known as an established drug for allergic disorders and branchal asthma. Charak has described it to be most effective vishghna (antitoxic drug). On Pharmacological study it is found to be antihistaminic and steroidogenc, plasma cortisol is increased within a week after the administration of the drug Active Principle is known to be a Saponin.

All above drugs may be used alone or in combination for the treatment of several types of respiratory system disease. Shirisadi compounds containing Shirisha, Kanthari, vasa and Madhyuasthi is popularly used as shiristi chey (tea). Sunthi.

Gastro – Intestinal: Statistics is evident that the incidence of gastro intestinal diseases in India is maximum. Broadly these can be classified in two groups (i) psychosomatic disease (ii) parasitic infection and a third group can be idiopathic. Among the first group peptic ulcer (parionon shula) irritable bowel syndrome and colitis are the common clinical entities available in our country. Ion the second group amoebiasis, giardiass and other worm infections are common e.g. round work, Hook worm, thread worm. There is a concept of Jatharagni in Ayurveda. Apart from that it also seems to help the absorption and metabolism. In case of hyperseoretion/Hyposecreation absorption becomes poor and the metabolism registers at a lowereble. So the malsecretion and malaobsoption syndrome are related to each other and produce several disease of G.I. tract which are often known as adiopathic e.g. Amlaphita, graham etc.

A good number of drugs have been worked out and found to be useful for the treatment of these disorders or follows :

Patola –    Gastritis

Nurikela – Pepticulcer

KLutaja –  Colis

Karanj –    Amoebiasis

Bilwa –      Amoebiasis

Palas –      Beeja – worm infections

Most of these drugs stimulate and digestive and help in regeneration of villi for a better absorption which leads to acceleration of metabolism. Some of the drugs are proved to be antihelimenthic and antiparasitic others offer symptomatic relief to the gastro intestinal symptoms.

Liver Dis-function:

The most common disease of liver is infective hepatitis (kamala) Though it is a fact that it is a self limiting disease and takes about 4 weeks to become alright but it has got a very deterimented effect on health, if the pathology continues come residual symptoms perrists it may turn into cirrhosis of liver which is fatel in due course of time.

Otherwise of the infection is fulminating it may take acute turn and patient may pass towards acute hepatic failure characterized by anasarca, hemorrhage, renal and curdic failure and the patient may succumb in no time.

Even in the normal course of the disease there can be four stages on the first week there is no jaundice, there is fever and loss of appetite and general weakness usually the cough and cold may be present with the beginning of the process. In the second week Jaundice is marked urine, stool, skin, nails, eyes everything becomes yellow, in the third week there may be inflammation of file canaliculi colangitis leading to intrapepaic obstruction and regurgitation of file in the blood producing a more deep Joundice and whiteclay colourd stool, in the fourth week the pathology may resolve  or pass to the stage of complication. Otherwise also, it the resolution is not complete the lesion may perrist as residual pepatitis. The following drugs hae been found to have a cholaratic effect and helping in the complete resolution of hepatitis, so these drugs have preventive as well as curative effect in patients of hepatitis.                                                                 
Kalmegh – Androgaphis panculata 
 Bhringraj – Eclipta alba
Amalaki – Emblica officinalis
Sarpankha – Tephrosia purpurea.

In clinical trial all these drugs in combination or as single drug can be used kalmegha and Amalaki combination are under clinical trial in our medicinal plants unit serum bilirubin comes down to normal range within to 2-3 weeks hepatitis is improved and there is no chance of having residual hepatitis in the end.

The discussion could be extended to any length but it is concluded with an optimistic note that India with its rich heritage of herbal medicine, its wealth of medicinal flora and necessary expertise in all relevant area would be able to offer leadership in the development of herbal medicine. It should, however be kept in mind that tomorrows citizens of India will have a better scientific temper and attitude and will not be satisfied to know merely that it works they will question how it works? Our development should be equipped to answer this questions.

Dhirendra V. Singh

4th Anniversary of Genelife Clinical Research

Not so long ago, on 26 Feb 2010 we started Genelife Clinical Research, after years of planning and analyzing the cost & expenses. On this day our dreams took-off with a lot of enthusiasm, promise and hope in the back drop of recession and limited resources. We knew that if we will survive that period we would have no limits. During those days we had to survive not only the recession but also against mighty established players. We survived that period and emerged as a winner in our own way. The first year was a very emotional year. We had gone through lots of pain and turbulence before we reached our 1st anniversary. But why I am talking about that now.. because this was an equally challenging year.

This year we will be remembering as the year of “reform and regret”. Across the country the quality of care of patients and clinical research was decreasing considerably. The necessary quality standards were available as standard in some places and were unavailable in others. Our regulation which was developed in a piecemeal fashion over a period of time was not able to manage the things properly and industry was in desperate need for reform- which finally happened this year. However, the planning, developing and implementation of this reform took almost a year, which almost killed the Clinical Research industry of India. Many competitor companies including some giants pull their curtains down; some changed their mode of operations. This changed the entire complexion of Clinical Research market, which to some extent is positive because now only those seriously involved companies are left in this serious business.

Everybody in healthcare industry was affected by this “silent” phase and we were no exception. However, with the confidence in our system and support of clients, friends and well-wishers we came out of this period. This could have been even better if we would have not lost some US FDA projects due to this regulatory complication. I still regret that decision of taking those projects in such an unstable regulatory environment. It was hard for us, but even larger concern and my deep apology to those sponsors whose time, energy and money wasted during this tenure.

Since inception, Genelife Clinical Research has focused on strong customer relationship with a vision "To be the most respected partner in providing product development and clinical research needs." The effort of giving the best is a kind of self-motivating mantra which probably separates us from the rest. And probably this is the only thing which helps us to emerge excellent from any given situation.

Looking back at the development of the entire year; it gives me a sense of achievement. We started the year on high note and anticipated a greater growth; however, with all the hiccups, what we achieved is remarkable growth not only in terms of project but also in terms of reach. We now have a global presence and soon we will be operating globally. We have implemented electronic CRF and looking forward to implement CTMS.

I would like to to attribute this year’s success to my team, which stuck to the basics & kept me away from taking any imprudent decisions. The secret of our success this year is not just doing the right thing but doing the right thing in customer centric way cost effectively. Very basic principle we understood our sponsor’s requirement and planned according to their requirement.

On this auspicious occasion, I sincerely appreciate the faith of clients on our ability. We are looking forward to deliver that trust in best possible way. I am greatful to all those who have directly or indirectly helped us to shape our dream and vision. But my greatest thanks to my colleagues and consultants for their commendable effort and believing the ideology of Genelife Clinical Research. This year belong to them and I feel proud to be a part of this excellent team.

I am looking forward for the same kind of trust, faith and support from everyone in future. I know if we perform this good, we will evolve even better in the coming year.

Thank You.

Kind Regards,

Dhirendra V. Singh

Genelife Clinical Research: Ophthalmology Clinical Trials

Genelife Clinical Research has started 12 Phase III Ophthalmology Clinical Trials for DCGI Submission. These 12 studies cover vide range of indications including dry eye, Ocular pain, Intra Ocular pressure, different types of conjunctivitis, pre & post cataract surgery etc. In these studies we are recruiting all kinds of patients from minor to old age people which will be a challenging task for us. 

We have already finished selecting sties for these studies. All the sites are selected very carefully as per the current DCGI guidelines including audio visual regulation. All these sites are multi-specialty/government hospitals with DCGI approved ethics committees and are distributed in all Geographical regions of India. During site selection we have considered seasonal variation as well as on recruitment prevalence of the particular ophthalmic condition from DSR, historic data and geographical location.

 

For adapting and absorbing the complexities aroused due the introduction of audio visual informed consent we have developed our electronic CRF which will be able to capture that also. This will help us to make a complete document for a patient for regulatory purpose and future regulatory audit purpose. During the site selection procedure we have made special emphasis on the infrastructure of site and computational knowledge of site personal.

Like our past studies we are hoping to complete these study before the time we proposed to our Sponsor. Hope we will achieve our target.
Kind Regards,

Rama Rajesh 

Project Manager 

Genelife Clinical Research

Genelife Clinical Research: III Anniversary

We perform at our intellectual best and by exceptional willingness when we know why and what we're doing; with this motivation Genelife Clinical Research was established (on 26th Feb 2010). Every one related to Genelife either employees, clients, consultants, investigators, vendors or well-wisher they all have played their role most effectively and efficiently in the establishment & development of Genelife Clinical Research. On the third anniversary of Genelife Clinical Research I would like to thank everybody who has worked to achieve our goal “To be the most respected partner in providing product development and clinical research needs.” We can say this, because we have been haired more than once by all our sponsors. 

The development of Genelife Clinical Research has proved that marketing and sales is not the only deciding factor for the development of an organization. Our continuous development is because of our young Operations & Biometrics team, which has shown the urge to reach their full potential in order to make each project successful. They proved that the strongest principle of growth lies in one’s choice. We were privileged to receive this choice from our esteemed clients who trusted in our capabilities and entrusted their important projects. Furthermore, our development is also credited to those clients who have given suggestions for process development in place of project, which was equally valuable. And with them we hope to strengthen our relation further. 

Genelife Clinical Research has seen several notable changes this year like: 

• Web CRF 
• New & bigger office 
• Global presence; we now have major clients in Australia, Europe & North America. And now we have operations in Malaysia, Sri Lanka, Bangladesh, Indonesia and South Africa. 

In 4th year of our business we will focus on accelerating our growth strategy while continuing to build on the strength of our brand—by sharing the knowledge of our services & strength through effective marketing. However, we will not follow the conventional method of marketing also. It will be as unique as our “Disease Surveillance Report”. We are very excited about this and truly believe that this will bring a trend in our fraternity. This will also be our first step towards expansion with stability, better service, and global presence while still offering all advantages of a small size CRO. We are also very excited for our new office in Copenhagen which we will open in May 2013. However, our focus will remain on “Creating Innovation” in our project management implementation. 

Looking back on the trails of time and development I feel proud to be a part of this exciting journey. This keeps me encouraged and intrigues me to reach further out to you, our partner, client and ambassador. 

Thank you everybody. 

Kind Regards,

Dhirendra V. Singh

Biosimilar Regulation in India

A biotherapeutic product which is similar in terms of quality, safety and efficacy to an already licensed reference biotherapeutic product is known as Biosimilar.

This could be the single fastest-growing biologics sector in the next five years – albeit from a small base – spurred by the convergence of major dynamics that will see new biosimilars enter the US market, bring additional molecules to Europe, and open up oncology and autoimmune disease areas to biosimilars for the first time ever. Biosimilars also bring clear potential for payers in the emerging pharmaceutical or “pharmerging” markets, such as Brazil, China and India. India have developed new regulatory guidelines for Biosimilar.

In New guideline DCGI has made mandatory the preclinical evaluation of biosimilar. The non-clinical studies should be comparative in nature and design to detect differences if any, between the similar biologics and innovator recombinant product. These should be conducted with the final formulation of the similar biologics intended for clinical use, unless otherwise justified. The non-clinical study design may vary depending upon the clinical parameters such as therapeutic index, the type and number of indications applied for etc. Assays like receptor binding studies or cell based assays (e.g. cell proliferation assays) should be conducted, when appropriate to establish comparability of biological activity. In cases where invitro assays do not reflect the pharamacodynamics, in-vivo studies should be performed. Comparative repeat dose toxicity with immunogenicity testing is also made compulsory in given route of administration, local tolerance should be evaluated.

According to new guideline, comparative Pharmacokinetic (PK) study on healthy subjects, Pharmacodynamics (PD) studies in most patients or healthy volunteers. If PD marker is available in healthy volunteers, PD in healthy volunteers can be done. Followed by a Phase III, Comparative safety and efficacy in relevant patient population is also mandatory for all biosimilar. However, in certain cases it can be waived. DCGI has also mandated the submission of PSUR 6 monthly for first 2 years and then annually for next 2 years, along with a Post Market study.

Regulatory applications and approvals issued at different stages of biosimilars product development

No.	Stage	Agency involved	Application	Approval
1	Manufacturing permission for test, analysis & examination	DCGI	Not Spesific	Permission (Manufacturing NOC)
2	Manufacturing License for test, analysis & examination	Local FDA	Form 30	Form 29
3	R & D	Institutional Biosafety Committee (IBSC)	Not Spesific	Permission (IBSC minutes)
4	Non-Clinical studies permission	RCGM	Form C3	Form C4
5	Submission of Non-clinical study report	RCGM	Form C5	Form C6
6	Clinical Trials	DCGI	Form 44	Permission (CT NOC)
7	Manufacturing License for CT batches	Local FDA (subject to CT NOC)	Form 30	Form 29
8	Manufacturing & Marketing permission	DCGI	Form 44	1. Form 45/46 (Finished product) 2. Form 46A (Bulk product)
9	Commercial Manufacturing License	Local FDA	Form 27 D	Form 28 D

Kind Regards,

Genelife Clinical Research- Ongoing Medical Device Clinical Trials

Genelife Clinical Research has started its first Medical Device Pilot Clinical Study for US FDA submission. Although we have participated in couple of US FDA studies in past but both were Pharmaceutical Clinical Trials. This is first time we are going to start a Medical Device Clinical Trials for Medical Device, within ENT therapeutic area. 

The study will be performed in a single site in India and we are hoping to recruit all patient volunteers in one month. The site selection procedure was dependent on not only the historic performance, type of Institute and its geographic location, paramedical staff, Investigator’s qualifications but we also considered the importance of patient referral. This we did considering the importance of project as well as the dependence of season on recruitment. 

Like our past studies we are hoping to complete this study before the time we proposed to our Sponsor. Hope we will achieve our target.

Kind Regards,

Advantages of eCase Report Form

No experiment is said to be complete until the results had been published or otherwise reported. It becomes even more important when the research directly involve human. Clinical research not only directly involves human subjects but can also affect human health if the reporting is not performed properly. And for proper reporting, proper data collection is very important.

In 70% clinical trials data collection is done manually through paper CRF in which Investigators manually record data on source documents and copy the same to the CRFs. Clinical monitors from CRO/sponsor verify the data and send the CRFs to CDM team. Paper CRF usually has an audit trail that is visible directly on the CRFs. Changes to individual fields are indicated with a single-line cross out, with the changed data appended along with the signature or initial of the person making the change, a date and perhaps a reason for change. Comments are written in the margin of these CRFs. Data clarification forms are appended to the CRF and contain the questions and responses that generated the change. This time honored format creates a complete case record with audit trail that is familiar to regulatory reviewers and investigators.

Though paper CRF gives an accurate, reliable and complete data, it is a laborious process and takes time for collecting CRF from investigational site, performing data entry and validation, and raising and resolving queries via Data Clarification Form (DCF). This has direct impact on time for drug to come in market. This suggested the idea of real time data management tools. Hence technology and innovation is used to its full extent and Electronic Data Capture (EDC) comes into limelight. The concepts for the design of electronic CRF are same as covered for paper.

EDC technology is expected to improve efficiency and accuracy of data, speed up decision making process and reduce cost. It resulted in a reduction of paper consumption and load on clinical monitors to manage such huge volume of paper. This paradigm has reduced the risk of damage of CRF during transit. It is due to these reasons EDC is preferred to traditional method.

GCP and 21 CFR Part 11 require validation for a software system used for processing clinical data. System validation includes user requirement specifications, functional specification, design specifications, implementation and testing. 21 CFR Part 11 defines the criteria under which electronic records and electronic signatures are considered to be trustworthy, reliable and equivalent to paper records. Part 11 has requirements to implement controls including audits, system validations, audit trails, electronic signature and documentation for software and systems involved in processing electronic data that are a) required to be maintained by FDA rules and b) demonstrate compliance to a predicted rule.

In electronic CRF, investigator enters data and signs electronically for accuracy, reliability and completion of all data points. It assembles data from multiple tables into a single Web page. However, the investigator later can add, modify or delete data in the EDC system in future at any time-point, until the electronic CRF are locked and no more updating is permitted. Investigator at this point should sign for the changes made to electronic CRF data points which were entered or changed. At the end, Investigator has to sign for all data entries, modifications or deletions as he is owner of that clinical data. This is why signing by the investigator is so important in electronic data capture.


Audit trails and comments are not found in the margins of an eCRF- they are viewable through links from the CRF and also are simply user-friendly representations of data tables. Electronic CRF is not just a repository but is designed to allow the backend systems to perform efficiently. The forms have built in edit checks and no longer accept entered data. POPs will appear if there is any error in entry/incorrect value. Query management can be done within minutes as opposite to paper CRF. Queries can be managed through computer user interface rather than paper based clinical trial. We can raise query directly on website and monitor can log on the query message and provide his resolutions there. Since high quality data are available at the time of data entry by the study site, biostatistician can review and analyze very early. As a result almost all statistical programs are completed before the visit of last patient.

Roles of data management staffs that have changed with the arrival of eCRF:

1. Data entry task shifted to site personnel/investigator 
2. Data review/cleaning became a joint venture of site personnel/investigator, clinical monitor and CDM team 
3. Trainer is needed in CDM to impact training functionality of EDC software 
4. Clinical monitors to perform source data verification which is a QC task, 
5. CDM members have to generate extra manual review listings and perform this task manually 
6. Clinical monitors or data management team to address/resolve technical issues faced by site personnel/investigators. 

However few challenges exist and researchers are trying to evaluate if quality of data produced by traditional paper based studies is better or equivalent compared to data generated by EDC. Investigational site personnel find data entry as a tedious task. Multiple EDC software has created confusion to non-CDM members. There is a need to develop effective training for EDC software, which is study specific for a given protocol. Hence investigational sites require technical support and guidance. One of the most common deficiencies cited by the FDA is the lack of documentation since the original observations are entered directly into a computer system; in this case electronic record becomes the source document. Paper is eliminated but EDC uses technologies like internet, software EDC and other additional services such as call center, so it cannot be considered as a cost-effective solution.

There is no doubt that electronic data capture is the future as it increases the speed of data processing and assures high quality data with lower error than paper CRF of Clinical Research. However, deployment of these advances should be implemented carefully as it requires consideration of desired outcome and the needs of people involved in the process.

Representing

Genelife Clinical Research - Clinical Data Management Department