A Study of

UNETHICAL PRACTICES
Practiced During

Objectives
I started my research with the following objectives: To identify and analyse the ethical and legal obligations upon a company conducting the clinical trials and drug development

To identify and analyze the unethical practices involved in clinical trials and drug development.

To suggest the remedial measures to ensure clinical trials and drug development tests be more ethical

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Table of Contents
S.No. Contents Page No. 1. Acknowledgement 2. Objectives 3. Table of Contents 4. Chapter I: Introduction: Ethics 5 5. Chapter II: Introduction: Clinical Trials 9 6.
Chapter III: Legal and Ethical Aspects: Clical Trials

2 3 4

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7.

Chapter IV: Pfizer Inc.: Clinical Trials: Model & Policy

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8. Chapter V: Clinical Trials: Critical Analysis 25 9. Chapter VI: Conclusion 29 10. Chapter VI: Recommendations 30 11. Bibliography 12. Annexure 31 33

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Chapter I : I NTRODUCTION

: E THICS

Ethics means Investigation into the basic

concepts and fundamental principles of human conduct. It includes study of universal values such as the essential equality of all men and women, human or natural rights, obedience to the law of land, concern for health and safety and, increasingly, also for the natural environment.
2

When most people think of

ethics (or morals), they think of rules for distinguishing between right and wrong, such as the Golden Rule ("Do unto others as you would have them do unto you"), a code of professional conduct like the Hippocratic Oath ("First of all, do no harm"), a religious creed like the Ten Commandments ("Thou Shalt not kill..."), or a wise aphorisms like the sayings of Confucius. However, the most common way of defining ethics is norms for

conduct that distinguish between acceptable and unacceptable behaviour of one . Another way of defining 'ethics' focuses on the disciplines that study standards of conduct, such as philosophy, theology, law, psychology, or sociology. For example, a "medical ethicist" is someone who studies ethical standards in medicine. One may also define ethics as a method, procedure, or perspective for deciding how to act and for analyzing complex problems and issues. Ethical norms serve the aims or goals of research and when it comes into the arena of research, it involves the application of fundamental ethical principles to a variety of topics involving scientific research.
http://triadwatch.blogspot.com/2009/09/ethics-ethics-ethics-greensboro-city.html http://www.businessdictionary.com/definition/ethics.html 3 www.web-miner.com/ .htm researchethics
1 2

These include the design and

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implementation of research involving human experimentation, animal experimentation, various aspects of academic scandal, including scientific misconduct (such as fraud, fabrication of data and plagiarism),whistle blowing; regulation of research, etc. The ethical norms apply to people, who conduct scientific research or other scholarly or creative activities, and there is a specialized discipline, research ethics, which studies these norms and therefore, it can be said that Research ethics is the most developed concept in medical research. There are many ethical issues to be taken into serious consideration for research. Sociologists need to be aware of having the responsibility to secure the actual permission and interests of all those involved in the study. They should not misuse any of the information discovered, and there should be a certain moral responsibility maintained towards the participants.

Reasons to follow Ethical Norms It is very essential to remain stick to the ethical norms while resea rch for the very simple following reasons:
4

The norms promote the aims of research

, such as For

knowledge, truth, and avoidance of error. example, prohibitions against fabricating, falsifying, or misrepresenting research data promote the truth and avoid error .

The ethical standards promote the values that are essential to collaborative work, such as trust, accountability, mutual respect, and fairness. For

example, many ethical norms in research, such as guidelines for authorship, copyright and patenting policies, data sharing policies, and confidentiality rules in peer review, are designed to protect

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intellectual property interests while encouraging collaboration

Many of the ethical norms help to ensure that researchers can be held accountable to the public. Ethical norms in research also help to build public support for research. People more likely to fund research project if they can trust the quality and integrity of research. Many of the norms of research promote a variety of other important moral and

social values , such as social responsibility, human rights, animal welfare, compliance with the law, and health and safety. Ethical lapses in research can significantly harm to human and animal subjects, students, and the public. For example, a researcher who fabricates

data in a clinical trial may harm or even kill patients and a researcher who fails to abide by regulations and guidelines relating to radiation or biological safety may jeopardize his health and safety or the health and safety of the staff and the students
.

There are a number of ethical principles which should be there in any code of ethics, designed specifically for a research objectives like:
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Objectivity

Strive to avoid bias in experimental

design, data analysis, data interpretation, peer review, personnel decisions, grant writing, expert testimony, and other aspects of research where objectivity is expected or required. Avoid or minimize bias or selfdeception. Disclose personal or financial interests that may affect research.

Integrity

Keep your promises and agreements; act

with sincerity; strive for consistency of thought and action.

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http://www.google.co.in/imgres?imgurl=http://www.abecsw.org/images/.....r:4,s:0 http://www.unisa.edu.au/policies/codes/ethics/ethics.asp Ibid .

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Carefulness

Avoid careless errors and negligence; carefully and critically examine your

own work and the work of your peers. Keep good records of research activities, such as data collection, research design, and correspondence with agencies or journals.

Openness
ideas.

Share data, results, ideas, tools, resources. Be open to criticism and new

Respect for Intellectual Property

Honor

patents, copyrights, and other forms of

intellectual property. Do not use unpubli shed data, methods, or results without permission. Give credit where credit is due. Give proper acknowledgement or credit for all contributions to research. Never plagiarize.

Confidentiality

Protect confidential communications, such as papers or grants

submitted for publication, personnel records, trade or military secrets, and patient records.

Responsible Mentoring

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Help to educate, mentor, and advise students. Promote their

welfare and all ow them to make their own decisions.

Social Responsibility -

Strive to promote social good and prevent or mitigate social

harms through research, public education, and advocacy.

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www.niehs.nih.gov/ Supra. 6 www.web-miner.com/

research

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Chapter II:

NTRODUCTION

: C LINICAL TRIALS

Clinical trials form an integral part of the drug discovery process worldwide. It is the set of practices required to certify a new drug molecule as safe and efficacious for the market. It is the research study that test, how well a new medical approach works in people. Each study answers scientific questions and tries to find better ways to prevent, screen for, diagnose or treat a disease. Clinical trials may also compare a new treatment to a treatment that is already available.
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Medical

research, in general, is a good thing and absolutely necessary to cure number of chronic diseases. At present in India we have 40 million asthmatic patients, about 34 million diabetic patients, 8-10 million people with HIV, 8 million epileptic patients, 3 million cancer patients, more than 2 million cardiac-related deaths, 1.5 million people with Alzheimers disease; 15% of the population is hypertensive, and 1% suffers from schizophrenia. In order to give best treatment to above diseases research on humans is both necessary and desirable.
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A clinical trial is defined as "any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes."
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The entire process of clinical trial is divided into four phases: Phase I: Small group of people (20-80), is tested upon for the first time in order to evaluate the safety, safe dosage range and the side-effects of the drug. Phase II: Group size is increased to a number of people approx 250, to see if it is effective and to further evaluate the study.
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http://www.nlm.nih.gov/medlineplus/clinicaltrials.html http://www.legalserviceindia.com/article/l286-Clinical-Trails-In-India.html Ibid .

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Phase III:

This time a very large group (1000-3000) is considered to confirm its effects, and side-effects, to compare it to the existing treatment and to collect information that will allow the experimental drug or treatment to be used safely.

Phase IV:

Post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

Clinical Trial Protocol The clinical trial protocol is a document used to gain confirmation of the trial design by a panel of experts. The document is designed very carefully to safeguard the health of the participants as well as answer specific research questions. A protocol describes the eligibility for participants; the schedule of tests, procedures, medications, and dosages; and the length of the study. While in a clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment.
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This not only assures safety and health of the trial subjects, but also provides an exact template for trial, conduct by investigators at multiple locations to perform the study in exactly the same way. This harmonization allows data to be combined collectively as though all investigators were working closely together.

Informed Consent An essential component of initiating a clinical trial is to recruit study subjects following procedures using a signed document called "informed consent
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Informed consent is a legally-defined process of a person being told about key facts involved in a clinical trial before deciding whether or not to participate. To fully describe participation to a candidate subject, the doctors and nurses involved in the trial explain the details of the study using terms the person will understand.
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http://clinicaltrials.gov/ct2/info/glossary www.issuesinmedicalethics.org/083or084.html
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Foreign language translation is provided if the participant's native language is not the same as the study protocol. The research team provides an informed consent document that includes trial details, such as its purpose, duration, required procedures, risks, potential benefits and key contacts. The participant then decides whether or not to sign the document in agreement. Informed consent is not an immutable contract, as the participant can withdraw at any time without penalty.
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Stages in Clinical Trial

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http://clinicaltrials.gov/ct2/info/understand#Q05

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Chapter III

: L EGAL

& E THICAL A SPECT : C LINICAL TRIALS

Global clinical research is exploring India. Yet, it is certainly not the West that is introducing clinical research to India. Two ancient scripts, Charaka Samhita (a textbook of medicine) and Sushruta Samhita (a textbook of surgery), compiled as early as 200 B.C. and 200 A. D. respectively, show Indias age-old proficiency in medical research. However, a lot has changed in the clinical research scenario since then. Today, clinical trials are conducted through a regulated approach following certain guidelines laid down by the International Conference on Harmonization (ICH), which is spearheaded by U.S.A., Europe and Japan. There are number of laws governing clinical research at the International Level and that of at the National Level. International Aspect There are many international instruments that confer and safeguard the rights of participants in clinical trials. Nuremberg Code, 1947 : First of its kind, which stated voluntary consent as an absolute requirement for any human subjects research. International Covenant on Civil and Political Rights 1966 consent for medical and scientific experiments. Declaration of Helsinki : Observed the fact that the human rights issues within the domain of public law and private law remedies such as negligence and the tort of trespass do not constitute a potent deterrent for unscrupulous researchers operating in under-developed countries where access to legal advice is scarce and/or prohibitively expensive and hence stated that the responsibility of any loss or damage to the subject or locality or the persons of the locality, where the research is conducted, shall be borne by the researcher itself. : Article 7 relates to

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The council for International Organisation of Medical Sciences (CIOMS) International Ethical Guidelines 1993; The International Conference on Harmonization of Technical Requirements for the registration of Pharmaceuticals for Human Use Good Clinical Practice: Consolidated Guidelines 1996: research. CIOMS; Recent Version:
states that

mandated the requirement of consent of the subject of the

the research is responsive to the health

needs and the priorities of the population or community in which it is to be carried out; and any intervention or product developed, or knowledge generated, will be made reasonably available for the benefit of that population or community. EU Good Practices in Clinical Trials; The Council of Europes Convention on Human Rights and Biomedicine on Biomedical Research and UNESCOs Universal Declaration on Bioethics and Human Rights developments in the field of medical research at International level. XVI International AIDS Conference, Toronto : UNAIDS put forward an ethical : Most recent

argument as to why trial participants that seroconvert during a trial do not require access to effective treatment and finally, settled down the issue by vesting a right i.e. right to have effective treatment, in the favour of trial participants.

In Nuremberg Code and in ICCPR, the consent would be necessary in all circumstances i.e. those who become unconscious due to an accident or disease or those who are mentally handicapped could not, if no standard treatment exists, be offered new therapeutic measures that might restore their health or save their lives. Furthermore, Article 7 of ICCPR is to be reads "No one shall be subjected to torture or to cruel, inhuman or degrading treatment or punishment. In particular, no one shall be subjected without his free consent to medical or scientific experimentation. Such a rigid interpretation would mean that the respective provisions exclude many of those they were designed to protect.
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However, the declaration of Helsinki paid attention to this aspect and made the necessary changes in it by allowing the surrogate consent in such cases.

Indian Scenario It is not that the clinical trials in India are solely governed by the instruments operating at the international level; rather India is having its own set of rules as well, although in conformity with the above-stated international instruments. Indian Acts/Orders related to Clinical Trials are: Drugs and Cosmetics Act 1940 Medical Council of India Act 1956, (amended in the year2002) Central Council for Indian Medicine Act 1970 Guidelines for Exchange of Biological Material (MOH order, 1997) The Biomedical Research on Human Subjects (regulation, control and safeguards) Bill - 2005

Even though we have number of legislations; the important one for clinical trials is The Indian Council of Medical Research (ICMR) 1947(amended in the year 2006), which was set up in order to foster a research culture in India, improve and develop infrastructure and foster community support. The Drugs and Cosmetics Act, The Medical Council of India (MCI) Act states that all clinical trials in India should follow the ICMR guidelines of 2000. The ICMR has a mechanism of review for its own institutions, and so do other government agencies. Every doctor is governed by the MCI Act. Any doctor doing wrong in a trial or in practice can be prosecuted and the hospital can be closed. The MCI Act is very strong; the MCI has the power to take punitive measures. The Drugs Controller General of India (DCGI) is responsible for regulatory approvals of clinical trials in India. The DCGIs office depends on external experts and other government agencies for advice. Additional permissions are required for the export of blood samples to foreign central laboratories. The ICMR has a Central Ethics Committee on Human Research (CECHR), of whose approval is must for carrying on with any of the clinical trial. This committee audits the functioning of this Institutional Ethics Committee (IEC). The recently amended Schedule Y of Drugs and Cosmetic Rules
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order the composition of the IEC as per the ICMR guidelines. The DCGIs office in collaboration with WHO, ICMR and many committed research professionals, has been conducting the training programs for members of the Ethics Committees across the country. ICMR Guidelines, 2006
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The ICMR guidelines has a specific Chapter i.e. Chapter III which governs specifically with the ethical issues in clinical trials. Following are the features of the chapter: It mandates the information (regarding type of study, duration, participants, effects and side-effects) to be given to the participants. It asks for the re-consent in certain cases where required. It allows the participants to withdraw their consent. It creates an obligation upon the investigators for any loss or damage caused to the participant or the locality, caused due to research. It asks the investigators to maintain confidentiality. It creates a right for the participants to be compensated for the experiment. It prescribes a procedure to be followed while selecting any special group like pregnant or nursing women, children, vulnerable group etc. It also asks the investigators to compensate all the victims of any accident, if happen due to the conduct of research. The guidelines also vests a right in the participants to have post-trial access of any type of medical assistance in case of requirement arises due to the participation in study. It also lays down certain guidelines in order to regulate the collaboration of Indian parties with the international/multinational/foreign players in the field, for carrying on research in India. It also regulates the relations of investigators/sponsors/ any other party to the research with the media. (A copy of the ICMR guidelines Chapter III is annexed herewith the project report for ready reference)

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http://icmr.nic.in/guidelines.htm
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Medical Council of India: Code of Ethics Regulations, 2002

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On April 6, 2002, Medical Council of India released a notification regarding Code of Ethics Regulations, 2002. Chapter 7 of The Regulation deals with The regulation in the chapter states here as under: Clinical drug trials or other research involving patients or volunteers as per the guidelines of ICMR can be undertaken, provided ethical considerations are borne in mind. Violation of existing ICMR guidelines in this regard shall constitute misconduct. Consent taken from the patient for trial of drug or therapy which is not as per the guidelines shall also be construed as misconduct .
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Misconduct .

This states that apart from International set of rules and regulations, India is having its own legislations as well to govern the issues, specifically pertaining to the ethical issues in regard to clinical trials. It is not necessary to remember again that the national legislations are also capable enough to curb any kind of unethical practices in clinical trials.

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http://www.mciindia.org/know/rules/ethics.htm The Code of Ethics Regulations, 2002; Chapter 7, Regulation 7.22

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Chapter IV:

FIZER

INC.: C

LINICAL

TRIALS: M

ODEL & P OLICY

Pfizer is the world's largest researchbased biomedical and pharmaceutical company. Their corporate headquarters is located in New York, with major research and development locations in the United States and England.
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Recent

innovations include Sutenta novel cancer medicine that both cuts off the blood supply that feeds tumors and destroys cellular reproduction, a nd Chantixa new prescription medicine and accompanying support plan designed specifically to help smokers quit. In 2008, Pfizer earned $64.4 billion in revenues and invested $8.1 billion in research and development.

RESEARCH AND DEVELPOMENT

Pfizer's research and development organization is headquartered in London. The company has R&D labs in the following locations: Groton, Connecticut; Sandwich, England; Nagoya, Japan; Amboise, France; La Jolla, California; Cambridge, Massachusetts; Ann Arbor, Michigan; Kalamazoo, Michigan;

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St. Louis, Missouri.

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In 2007, Pfizer invested $100 billion in research a nd development, the largest investment in R&D by private biomedical research organization.

PFIZER POLICY ON GLOBAL CLINICAL TRIAL STANDARDS

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GCP & Ethics Compliance : All trials to be conducted incompliance with relevant international standards, including ICH GCP, with IRB/IEC review, locally wherever available. Diversity : Pfizer supports racial gender, and ethnic diversity, including representation of relevant subject groups in research protocols and among investigators. Informed Consent : Voluntary, tailored to

meet local laws, customs, and culture. Use of placebo and appropriate controls Control group must receive established effective treatment that is medically and ethically appropriate for the study. Placebo controls are allowable if there is no undue risk to health or well-being of participants. Locale and benefit to Host country benefit each host countrys population. Post-trial Access study drug. Support for study conduct : Governs Pfizer commitment of necessary : Specifies in the IC the conditions for continued receipt of : Research must have the potential to :

infrastructure and technological knowledge to adequately and appropriately conduct trials in low resource countries.

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Ibid. http://www.pfizer.com/research/science_policy/global_clinical_trial_standards.jsp
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IDENTIFICATION OF STAKEHOLDERS MORAL RESPONSIBILITIES IN PFIZER POLICY

RESPONSIBILITIES OF SPONSOR Providing Information Throughout the clinical trial, the sponsor is responsible for accurately informing the local site investigators of the true historical safety record of the drug, device or other medical treatments to be tested, and of any potential interactions of the study treatment(s) with already approved medical treatments.
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This allows the local investigators to make an informed judgment on whether to participate in the study or not.

Monitoring The sponsor is responsible for monitoring the results of the study as they come in from the various sites, as the trial proceeds.

Reporting of adverse events The sponsor is responsible for collecting adverse event reports from all site investigators in the study, and for informing all the investigators of the sponsor's judgment as to whether these adverse events were related or not related to the study treatment.
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This is an area where sponsors can slant their judgment to favour the study treatment.

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www.aes.asn.au/publi cations/Vol2No1/ stakeholder http://www.gts-translation.com/medicaltranslationpaper.pdf

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Writing site specific Informed consents The sponsor and the local site investigators are jointly responsible for writing a site-specific informed consent that accurately informs the potential subjects of the true risks and potential benefits of participating in the study, while at the same time presenting the material as briefly as possible and in ordinary language.

Safety concerns Responsibility for the safety of the subjects in a clinical trial is shared between the sponsor, the local site investigators (if different from the sponsor), the various IRBs that supervise the study, and (in some cases, if the study involves a marketable drug or device) the regulatory agency for the country where the drug or device will be sold.

RESPONSIBILITIES OF LOCAL SITE INVESTIGATORS

To follow the study protocol

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The local investigators are responsible for conducting the study according to the study protocol, and supervising the study staff throughout the duration of the study.

To take the decision to stop the study A physician's first duty is to his/her patients, and if a physician investigator believes that the study treatment may

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be harming subjects in the study, the investigator can stop participating at any time.

Reviewing and reporting of adverse events The local investigators are responsible for reviewing all adverse event reports sent by the sponsor. (These adverse event reports contain the opinion of both the investigator at the site where the adverse event occurred, and the sponsor, regarding the relationship of the adverse event to the study treatments).

RESPONSIBILITIES OF IRBs Approval by an IRB, or ethics board, is necessary before all but the most informal medical research can begin. In commercial clinical trials, the study protocol should be approved by an IRB before the sponsor recruits sites to conduct the trial. The IRB scrutinizes the study for both medical safety and protection of the patients involved in the study, before it allows the researcher to begin the study.
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However, the study protocol and procedures may have been tailored to fit generic IRB submission requirements.

RESPONSIBILITIES OF REGULATORY AGENCIES If a clinical trial concerns a new regulated drug or medical device (or an existing drug for a new purpose), the appropriate regulatory agency for each country where the sponsor wishes to sell the drug or device is supposed to review all study data before allowing the drug/device to proceed to the next phase, or to be marketed. However, if the sponsor withholds negative data, or misrepresents
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www.allacademic.com/meta/p229611_index.html http://www.gts-translation.com/medicaltranslationpaper.pdf
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data it has acquired from clinical trials, the regulatory agency may make the wrong decision. In the U.S., the FDA can audit the files of local site investigators after they have finished participating in a study, to see if they were correctly following study procedures.

RESPONSIBILITIES OF PATIENTS/VOLUNTEERS

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In Phase I drug trials; participants are paid because they give up their time (sometimes away from their homes) and are exposed to unknown risks, without the expectation of any benefit. In most other trials, however, patients are not paid, in order to ensure that their motivation for participating is the hope of getting better or contributing to medical knowledge, without their judgment being skewed by financial considerations.

ETHICS AND CLINICAL TRIALS: THE PFIZER WAY

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Pfizer has a policy on global clinical trial standards to ensure the ethical clinical research Pfizer maintains a long-standing commitment to ethical research. Pfizer regularly engages with international organizations regarding ethical issues in clinical research e.g. World Medical Association regarding revision of Declaration of Helsinki Pfizer follows ICH GCP, DOH, Belmont Report standards everywhere they do research All trials are first approved by applicable National Regulatory framework and appropriate local Ethical Committee review and oversight. Pfizers current investigators training program, Conducted globally in over 25 different countries; translated in 7 languages

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www.aes.asn.au/publications/Vol 2No1/ _ research stakeholder http://www.pfizer.com/research/science_policy/global_clinical_trial_standards.jsp

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PFIZER: GLOBAL POLICY FOR CLINICAL RESEARCH

In order to address these concerns, Pfizer listened to stakeholders and decided to take action. In 2005, Pfizer established the Global Policy on Interactions with Healthcare Professionals that introduced new guidelines to meet the needs of clinical research. This policy further solidified Pfizer's commitment to clinical research based on the highest standards. The new Global Policy incorporates common legal and ethical standards from many of Pfizer's major markets, including the US (Pfizer White Guide) and Europe (EFPIA Code on Promotion of Medicines) and applies them to operations in 180 countries.

Pfizer policies are based on the principles of maintaining ethics and compassion, building greater transparency and partnering to facilitate access to healthcare information and medicines. The four guiding principles of this policy are as follows:

Primacy of the healthcare professional and patient relationship Pfizer recognizes that the primary duty of practicing healthcare professionals is to their patients. Fundamentally, interactions with healthcare professionals must advance patient care and support the ethical and compassionate practice of medicine.

Corporate citizenship Pfizer demonstrates this commitment by: Developing new medicines Working with other stakeholders to make medicines and other healthcare information available to patients and HCPs

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Supporting the creation and implementation of sustainable healthcare solutions

Transparency Pfizer supports the disclosure of financial and other interests and relationships that may create apparent or perceived conflicts of interest in research, education or clinical practice and comply with all applicable laws, while dealing with HCPs employed by, or affiliated with government or regulatory authorities.

Educational grants Pfizer provides educational grants to support bona fide independent educational programs. Pfizer supports these programs to facilitate lifelong learning by healthcare professionals, ultimately to enhance patient care.

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Chapter V : C LINICAL

TRIALS: C RITICAL

ANALYSIS

However, it seems that there is everything fit and fine and everything moves smooth on the way, but the facts denied this statement. Critical trials.ohhh SorryClinical Trials have many critics associated with it like:

However, the trials should be taken up evenly, throughout the circumference of the globe; but the fact is that mostly the developing or the undeveloped nations are targeted for the task. Reason being: Costs are 10-50% lower than in traditional research areas. Furthermore, less strict (or lack of) legislation helps research protocols to be easier and earlier accepted. If preparatory procedures take less time, more years for profit making within the patent period remain. Another pull factor is the fact that volunteers for trials are more easily found. This is partly because populations are larger and thus more patients with a certain disease are available. Yet, in many cases participation in a trial is the only chance for a patient to receive any treatment at all, and often the (financial) incentives form an important encouragement. A medical argument for testing in developing countries is that the outcome of research has a higher validity if the subjects of study have received less medication (similar to the one studied) before participating in the trial. Finally, there are high economical benefits for hosting governments, an important incentive to relocate trial venues to their countries.

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Many drugs that are assumed to be effective are probably little better than placebos, but there is no way to know because negative results are hidden; as the favourable results were published and unfavourable results were buried. The public and the medical profession believed these drugs were potent. Clinical trials are also biased through designs for research that are chosen to yield favourable results for sponsors. For example, the sponsor's drug may be if compared with another drug administered, the result would be that a dose is so low that the sponsor's drug looks more powerful. Or a drug that is likely to be used by older people will be tested in young people, so that side effects are less likely to emerge. A common form of bias stems from the standard practice of comparing a new drug with a placebo, when the relevant question is how it compares with an existing drug.

LIVE INSTANCES OF UNETHICAL PRACTICES

The recent past is full of such instances, where the so called code of ethics, passed by the researchers while conducting the research:

was

Pfizer's Unapproved Drug Tested On Nigerian Children o A panel of Nigerian medical experts has concluded that Pfizer Inc. violated international law during a 1996 epidemic by testing an unapproved drug on children with brain infections at a field hospital; without obtaining prior authorization from the Nigerian government to give the unproven drug to nearly 100 children and infants. Pfizer selected the patients at a field hospital in the city of Kano, where the children had been taken to be treated for an often deadly strain of meningitis.
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Experimental Cancer Drug Tested Without People's Consent

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In November 1999, 25 people with oral cancer who went to the government-run Regional Cancer Centre in Thiruvananthapuram were given an experimental drug, though there was an established treatment for their condition. They were not told that they were taking part in an experiment or that they were being denied an established treatment. Only later did it become known that the trial had not been approved by the Drugs Controller of India (approval was obtained retroactively).

Diabetes drug tested on humans before toxicology studies completed o In 2002, the multinational company Novo Nordisk conducted multicentre phase III clinical trials of a diabetes drug before receiving the results of animal studies. The study report found that the drug, caused urinary bladder tumors in rats and this should have been known before the drug went for phase I trials, let alone phase II and phase III. The drug was developed by Dr Reddy's Laboratories, Hyderabad, and licensed to Novo Nordisk which conducted the trials.
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The trials were conducted on 650 people from North America,

200 from Latin America, 100 from Australia / New Zealand, 800 from the European Union, and 200 from non EU Europe- -and 550 from Asia including 130 people from eight centres in India. Half of these people received the experimental drug.

Drug promotion as "research" o In 2003, Mumbai-based Sun Pharmaceutical Industries Limited launched a promotional-cum-"research" program by getting private doctors to prescribe the anti-cancer drug to more than 400 women as a fertility drug for ovulation induction. They then publicized the doctors' reports to other doctors as "research", using their network of medical representatives.
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As a result Off-label prescription of drugs

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was banned in India, prompting the Indian Medical Association to launch a campaign to permit off-label prescription.

Research in emergency situations o In 2005 the drug company Santa Biotech ran a bioequivalence study testing its version of the "clot-buster" streptokinase against the established one. Streptokinase is given as emergency life-saving treatment to stroke patients. While there were various controversies about whether the company had taken the correct permissions to conduct the study, the important questions are: could the patients have given their consent to participate in the trial? NO.

Drug to prevent cervical cancer tested without approval o

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In 2008, the Centre ordered suspension of clinical trials on tribal girl students in Andhra Pradesh and Guja rat, carried out by a nongovernmental organisation, Path-International, for U.S-based pharmaceutical company MERCK for HPV (human papilloma virus) virus to prevent cervical cancer. While, it is believed permission had been granted for carrying out such trials, there was violation of guidelines on the ground and this became known after some girls reported adverse side-effects.

Monetary Rewards and Foreign Trips o

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In a recent episode of 2009 in Indore, doctors were accused of carrying out clinical trials for a multinational drugs company on patients without obtaining their consent, which is mandatory as per the guidelines of the Drugs Controller-General of India (DCGI). The doctors are also reported to have been given monetary incentives and free foreign trips for carrying out the trials.

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Chapter VI:

Conclusion

In short, according to my analysis, it is often possible to make clinical trials come out pretty much any way you want, which is why it's so important that investigators be truly disinterested in the outcome of their work. It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines.

Pfizer conducted its research in developing countries, but as soon as they get the patent of the particular drug, they sell the drug in their own countries. But ethics says that at least some benefits should be provided

to the nation where study was performed and benefits should be given to the volunteers who were suffering from that particular disease. The pharmaceutical industry faces challenges with respect to ethical practices. The above-stated two points and the whole discussion in the paper are evidencing the same. The conflict of commercial interests with adherence to ethical practices has been a subject of much deliberation. While such debates tend to have a high degree of subjective and emotive content, it is also a concern for quality healthcare. This is true not only in India, but it is a universal phenomenon common to many countries. The degree of concern varies depending on the laws and regulations in various markets and overall operating environment. Clinical Trials, which should aimed and focused at public welfare, are in fact aiming at profit and personal gains; nothing more than that.

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Chapter VI:

Recommendations

After analyzing the situation, following recommendations may be made in order to ensure clinical trials to be more ethical:

The members of medical school faculties who conduct clinical trials should not be allowed to accept any payments from drug companies except research support, and that support even should be routed through the Ethics Committee, under the health ministry of the nation. Again it should have no strings attached, including control by the companies over the design, interpretation, and publication of research results.

Responsibility of any disease or any adverse drug reaction, arise after any time period, but due to the research, shall be borne by the investigators. More Stringent should the legal structure be CLINICAL ESTABLISHMENTS (REGISTRATION AND REGULATION ACT) BILL, 2010 should be passed, which demands mandatorily from all the clinical establishments to provide for medical care and treatment to stabilize any person in an emergency condition. The instances of violation of medical ethics, which at present are covered under IPC, shall then be covered under this new Act. At present, the provision is just to cancel the license of the defaulter, to practice anymore and no punishment is prescribed for the offence of any unethical practice, whereas it should be clubbed with stringent punishment as well.

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Bibliography
Acts, Regulations and Guidelines: Drugs and Cosmetics Act Medical Council of India Act ICMR Guidelines Code of Ethics Regulations, 2002 Ethical Guidelines For Biomedical Research On Human Participants

Articles: The Process of Obtaining Informed Consent Bio-business in brief: The challenges of clinical trials Clinical trials in India: ethical concerns Report of Workshop on Insurance Issues in Clinical Trials : Indian Scenario SCIENTIFIC MISCONDUCT, THE PHARMACEUTICAL INDUSTRY, AND THE TRAGEDY OF INSTITUTIONS Websites:
http://www.legalserviceindia.com/article/l286-Clinical-Trails-In-India.html http://www.scribd.com/doc/7218924/ICMR-Ethical-Guidelines-India http://www.ijme.in/084or119.html http://icmr.nic.in/guidelines.htm http://www.thehindu.com/news/national/article544767.ece http://www.mciindia.org/know/rules/ethics.htm http://www.wordiq.com/definition/Medical_ethics http://www.nlm.nih.gov/medlineplus/clinicaltrials.html http://clinicaltrials.gov/ct2/info/understand#Q05 http://www.pharmafocusasia.com/clinical_trials/ethics_clinical_trials.htm
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http://triadwatch.blogspot.com/2009/09/ethics-ethics-ethics-greensborocity.html http://www.businessdictionary.com/definition/ethics.html www.web-miner.com/researchethics.htm www.issuesinmedicalethics.org/083or084.html

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Annexure
ICMR GUIDELINES CHAPTER III

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