he research protocol must be submitted for consideration, comment, guidance

and approval to the concerned research ethics committee before the study
begins. This committee must be transparent in its functioning, must be
independent of the researcher, the sponsor and any other undue influence
and must be duly qualified. It must take into consideration the laws and
regulations of the country or countries in which the research is to be
performed as well as applicable international norms and standards but these
must not be allowed to reduce or eliminate any of the protections for
research subjects set forth in this Declaration.

The committee must have the right to monitor ongoing studies. The
researcher must provide monitoring information to the committee, especially
information about any serious adverse events. No amendment to the protocol
may be made without consideration and approval by the committee. After the
end of the study, the researchers must submit a final report to the
committee containing a summary of the study’s findings and conclusions.

## PRIVACY AND CONFIDENTIALITY

Every precaution must be taken to protect the privacy of research subjects
and the confidentiality of their personal information.

## INFORMED CONSENT

25) Participation by individuals capable of giving informed consent as

subjects in medical research must be voluntary. Although it may be
appropriate to consult family members or community leaders, no individual
capable of giving informed consent may be enrolled in a research study
unless he or she freely agrees.

26) In medical research involving human subjects capable of giving informed

consent, each potential subject must be adequately informed of the aims,
methods, sources of funding, any possible conflicts of interest,
institutional affiliations of the researcher, the anticipated benefits and
potential risks of the study and the discomfort it may entail, post-study
provisions and any other relevant aspects of the study. The potential
subject must be informed of the right to refuse to participate in the study
or to withdraw consent to participate at any time without reprisal. Special
attention should be given to the specific information needs of individual
potential subjects as well as to the methods used to deliver the
information.

After ensuring that the potential subject has understood the information,
the physician or another appropriately qualified individual must then seek
the potential subject’s freely-given informed consent, preferably in
writing. If the consent cannot be expressed in writing, the non-written
consent must be formally documented and witnessed.

All medical research subjects should be given the option of being informed
about the general outcome and results of the study.

27) When seeking informed consent for participation in a research study the
physician must be particularly cautious if the potential subject is in a
dependent relationship with the physician or may consent under duress. In
such situations the informed consent must be sought by an appropriately
qualified individual who is completely independent of this relationship.

28) For a potential research subject who is incapable of giving informed

consent, the physician must seek informed consent from the legally
authorised representative. These individuals must not be included in a
research study that has no likelihood of benefit for them unless it is
intended to promote the health of the group represented by the potential
subject, the research cannot instead be performed with persons capable of
providing informed consent, and the research entails only minimal risk and
minimal burden.

29) When a potential research subject who is deemed incapable of giving

informed consent is able to give assent to decisions about participation in
research, the physician must seek that assent in addition to the consent of
the legally authorised representative. The potential subject’s dissent
should be respected.

30) Research involving subjects who are physically or mentally incapable of

giving consent, for example, unconscious patients, may be done only if the
physical or mental condition that prevents giving informed consent is a
necessary characteristic of the research group. In such circumstances the
physician must seek informed consent from the legally authorised
representative. If no such representative is available and if the research
cannot be delayed, the study may proceed without informed consent provided
that the specific reasons for involving subjects with a condition that
renders them unable to give informed consent have been stated in the
research protocol and the study has been approved by a research ethics
committee. Consent to remain in the research must be obtained as soon as
possible from the subject or a legally authorised representative.

31) The physician must fully inform the patient which aspects of their care
are related to the research. The refusal of a patient to participate in a
study or the patient’s decision to withdraw from the study must never
adversely affect the patient-physician relationship.

32) For medical research using identifiable human material or data, such as
research on material or data contained in biobanks or similar repositories,
physicians must seek informed consent for its collection, storage and/or
reuse. There may be exceptional situations where consent would be
impossible or impracticable to obtain for such research. In such situations
the research may be done only after consideration and approval of a
research ethics committee.

## USE OF PLACEBO

33) The benefits, risks, burdens and effectiveness of a new intervention

must be tested against those of the best proven intervention(s), except in
the following circumstances:

Where no proven intervention exists, the use of placebo, or no

intervention, is acceptable; or

Where for compelling and scientifically sound methodological reasons the

use of any intervention less effective than the best proven one, the use of
placebo, or no intervention is necessary to determine the efficacy or
safety of an intervention

and the patients who receive any intervention less effective than the best
proven one, placebo, or no intervention will not be subject to additional
risks of serious or irreversible harm as a result of not receiving the best
proven intervention.

Extreme care must be taken to avoid abuse of this option.

## POST-TRIAL PROVISIONS

34) In advance of a clinical trial, sponsors, researchers and host country

governments should make provisions for post-trial access for all
participants who still need an intervention identified as beneficial in the
trial. This information must also be disclosed to participants during the
informed consent process.

## RESEARCH REGISTRATION AND PUBLICATION AND DISSEMINATION OF RESULTS

35) Every research study involving human subjects must be registered in a

publicly accessible database before recruitment of the first subject.

36) Researchers, authors, sponsors, editors and publishers all have ethical
obligations with regard to the publication and dissemination of the results
of research. Researchers have a duty to make publicly available the results
of their research on human subjects and are accountable for the
completeness and accuracy of their reports. All parties should adhere to
accepted guidelines for ethical reporting. Negative and inconclusive as
well as positive results must be published or otherwise made publicly
available. Sources of funding, institutional affiliations and conflicts of
interest must be declared in the publication. Reports of research not in
accordance with the principles of this Declaration should not be accepted
for publication.

## UNPROVEN INTERVENTIONS IN CLINICAL PRACTICE

37) In the treatment of an individual patient, where proven interventions

do not exist or other known interventions have been ineffective, the
physician, after seeking expert advice, with informed consent from the
patient or a legally authorised representative, may use an unproven
intervention if in the physician's judgement it offers hope of saving life,
re-establishing health or alleviating suffering. This intervention should
subsequently be made the object of research, designed to evaluate its
safety and efficacy. In all cases, new information must be recorded and,
where appropriate, made publicly available.

## ARTICLE INFORMATION

Corresponding Author: World Medical Association, 13, ch. du Levant, CIB -

Bâtiment A, 01210 Ferney-Voltaire, France; wma@wma.net.

Published Online: October 19, 2013. doi:10.1001/jama.2013.281053.

Disclaimer: ©2013 World Medical Association, Inc. All Rights Reserved. All
intellectual property rights in the Declaration of Helsinki are vested in
the World Medical Association. The WMA has granted JAMA exclusive rights to
publish the English-language version of the Declaration through December
31, 2013.

Online-Only Content: Audio podcast is available at www.jama.com.

Copyright ©2013 American Medical Association

## SOURCE

http://www.wma.net/en/30publications/10policies/b3/

The Clinical Trials Registry- India (CTRI), hosted at the ICMR's National Institute of
Medical Statistics (http://nims-icmr.nic.in), is a free and online public record system for
registration of clinical trials being conducted in India that was launched on 20th July 2007
(www.ctri.nic.in). Initiated as a voluntary measure, since 15 th June 2009, trial
registration in the CTRI has been made mandatory by the Drugs Controller General
(India) (DCGI) (www.cdsco.nic.in). Moreover, Editors of Biomedical Journals of 11 major
journals of India declared that only registered trials would be considered for publication 1,
2
.

Today, any researcher who plans to conduct a trial involving human participants, of any
intervention such as drugs, surgical procedures, preventive measures, lifestyle
modifications, devices, educational or behavioral treatment, rehabilitation strategies as
well as trials being conducted in the purview of the Department of AYUSH
(http://indianmedicine.nic.in/) is expected to register the trial in the CTRI before
enrollment of the first participant. Trial registration involves public declaration and
identification of trial investigators, sponsors, interventions, patient population etc before
the enrollment of the first patient. Submission of Ethics approval and DCGI approval (if
applicable) is essential for trial registration in the CTRI. Multi-country trials, where India
is a participating country, which have been registered in an international registry, are
also expected to be registered in the CTRI. In the CTRI, details of Indian investigators,
trial sites, Indian target sample size and date of enrollment are captured. After a trial is
registered, trialists are expected to regularly update the trial status or other aspects as
the case may be. After a trial is registered, all updates and changes will be recorded and
available for public display.

Being a Primary Register of the International Clinical Trials Registry Platform (ICTRP)
(http://www.who.int/ictrp/search/en/), registered trials are freely searchable both from
the WHO's search portal, the ICTRP as well as from the CTRI (www.ctri.nic.in).
[Read more...]
The Tuskegee Study of Untreated Syphilis in the Negro Male was a clinical study, conducted
between 1932 and 1972 in Tuskegee, Alabama, in which 399 (plus 201 control group without
syphilis) poor — and mostly illiterate — African American sharecroppers were denied treatment for
Syphilis.
This study became notorious because it was conducted without due care to its subjects, and led to
major changes in how patients are protected in clinical studies. Individuals enrolled in the
Tuskegee Syphilis Study did not give informed consent and were not informed of their diagnosis;
instead they were told they had “bad blood” and could receive free medical treatment, rides to the
clinic, meals and burial insurance in case of death in return for participating.

In 1932, when the study started, standard treatments for syphilis were toxic, dangerous, and of
questionable effectiveness.

Part of the original goal of the study was to determine if patients were better off not being treated
with these toxic remedies.

For many participants, treatment was intentionally denied. Many patients were lied to and given
placebo treatments—in order to observe the fatal progression of the disease.

By the end of the study, only 74 of the test subjects were still alive. Twenty-eight of the men had
died directly of syphilis, 100 were dead of related complications, 40 of their wives had been
infected, and 19 of their children had been born with congen

Nazi human experimentation was medical experimentation on large numbers of people by the
German Nazi regime in its concentration camps during World War II.

At Auschwitz, under the direction of Dr. Eduard Wirths, selected inmates were subjected to various
experiments which were supposedly designed to help German military personnel in combat
situations, to aid in the recovery of military personnel that had been injured, and to advance the
racial ideology backed by the Third Reich.

Experiments on twin children in concentration camps were created to show the similarities and
differences in the genetics and eugenics of twins, as well as to see if the human body can be
unnaturally manipulated. The central leader of the experiments was Dr. Josef Mengele, who
performed experiments on over 1,500 sets of imprisoned twins, of which fewer than 200
individuals survived the studies.

Dr. Mengele organized the testing of genetics in twins. The twins were arranged by age and sex
and kept in barracks in between the test, which ranged from the injection of different chemicals
into the eyes of the twins to see if it would change their colors to literally sewing the twins
together in hopes of creating conjoined twins.

In 1942 the Luftwaffe conducted experiments to learn how to treat hypothermia. One study forced
subjects to endure a tank of ice water for up to three hours (see image above). Another study
placed prisoners naked in the open for several hours with temperatures below freezing. The
experimenters assessed different ways of rewarming survivors.

From about July 1942 to about September 1943, experiments to investigate the effectiveness of
sulfonamide, a synthetic antimicrobial agent, were conducted at Ravensbrück.

Wounds inflicted on the subjects were infected with bacteria such as Streptococcus, gas gangrene,
and tetanus. Circulation of blood was interrupted by tying off blood vessels at both ends of the
wound to create a condition similar to that of a battlefield wound. Infection was aggravated by
forcing wood shavings and ground glass into the wounds.
The infection was treated with sulfonamide and other drugs to determine their effectiveness.
[divider]
Source | DailyCognitio

MCI Suspends 8 Indore doctors’ Registration Over

Unethical Drug Trial

Indore docs flout clinical trial norms, earn lakhs

Rema Nagarajan| TNN | Jun 3, 2011, 05.49 AM IST
INDORE: Nearly 40 doctors and 18 hospitals in Indore, from both the
government and the private sector, are being investigated for malpractices in
clinical trials conducted by them. This follows shocking revelations of the
details of some of these medical trials.

For instance, over 1,100 children have been used in clinical trials from which
doctors in a leading government medical college earned lakhs of rupees. In one
shocking case, out of the nine subjects of a trial on the possible use of the drug
tadalafil in pulmonary hypertension (otherwise used for male erectile
dysfunction), seven were women and one was a 17-year-old boy, all from poor
families.

Replying to an RTI application filed by health activists, the Madhya Pradesh

legislative assembly gave details of clinical trials conducted by various doctors
in MGM Medical College and associated
M Y Hospital amounting to lakhs of rupees in the period 2005-10. Dr Hemant
Jain of paediatrics made Rs 56 lakh, Dr Anil Bharani of cardiology made Rs 44
lakh, Dr Apoorva Pauranik of neurology made Rs 42 lakh, Dr Ashok Bajpai of
medicine made Rs 41.37 lakh and Dr Salil Bhargava of chest and TB made Rs
40.19 lakh. In comparison, the take-home salary of the senior most professor at
MGM Medical College is Rs 75,000. Clearly, the clinical trials are the dominant
source of income for these doctors.

According to an editorial in the latest issue of the Monthly Index of Medical

Specialties (MIMS), during 2005-10, of the 2,365 patients enrolled for clinical
trials in five medical colleges in Madhya Pradesh, just six doctors in MGM
Medical College and associated M Y Hospital recruited 1,521 patients, the bulk
of them — 1,170 — were children.

Even though all the patients were recruited through the medical college, which
was the trial site, and the facilities of the hospital were used to conduct
investigations on the trial participants, the college got nothing from the lakhs
earned through these trials as the doctors received all the money in their
personal accounts. In an RTI reply this month, the college authorities admitted
that the college had not earned any money from clinical trials in the last five
years.

A clinical trial agreement between Dr Pushpa Varma, professor of

ophthalmology, and a clinical research organization, Quintiles Research (India)
Private Ltd, for a pharma company called Alcon gives an idea of how the
money is diverted. In the agreement, the payment was to be made to "Dr Pushpa
Varma, MGM Medical College and M Y Hospital, 61 Juni Kasera Bakhal,
Indore-452001", which is her private address and not that of the college and she
gave her own PAN number, so that all the money was credited to her account.
Dr Varma was paid Rs 26,000 per patient enrolled in the trial to test the eyedrop
moxifloxacin of Alcon. With 35 patients, she pocketed a cool Rs 9 lakh.

"In the case of 15 clinical trials, instead of obtaining permission from the on-site
ethics committee of the medical college, permission has been obtained from
strange non-verifiable entities claiming to be ethics committees located
thousands of kilometers away in Pune or Ahmedabad," pointed out MIMS
editor Dr C M Gulati.

After the issue of clinical trials was raised in the assembly last year, two
committees were constituted, one by the secretary of medical education and
another by the health department headed by chief medical and health officer Dr
Sharad Pandit. While the medical education committee is yet to submit its
report, Dr Pandit has submitted a preliminary report which has raised concerns
about ethics committees being constituted against norms. Dr Pandit's committee
noted how a trial located in the medical college got approval from the ethics
committee of a private hospital and other such irregularities. The final report of
the CMHO's five-member committee is India is fast emerging as one of the global hubs for
conducting clinical trials. This is due to the so called “India Advantage” which includes availability of large
numbers of patients, highly motivated and skilled medical and paramedical personnel, state of the art
hospitals and strong information technology (IT) support. O expected within a week.
Members of Swasthya Adhikar Manch, a network of NGOs who had filed
several RTI applications to expose the manner in which clinical trials were
being conducted, have expressed concern over the lack of any government
action. "The issue was raised last year. The accused doctors continue to hold
their positions. They can easily influence the poor patients who they enrolled
for the trials and manipulate documents. They should have been transferred to
ensure free and fair probe," said Amulya Nidhi, one of the members of the
Manch.

The medical superintendent of M Y Hospital Dr Salil Bhargava and former dean

of MGM medical college Dr M K Saraswat when contacted refused to comment
saying that the matter was before the state assembly.

During 2005-10, doctors in MGM Medical College and MY Hospital made Rs

40-56 lakh. The take-home salary of the seniormost professor at MGM Medical
College is Rs 75,000.
According to documents submitted in the apex court, the psychiatrists had enrolled 233 mentally ill patients in clinical
trials without informed consent. Photo: Mint

New Delhi: Madhya Pradesh may suspend 11 doctors associated with the Mahatma Gandhi Medical
College (MGMC) in Indore for conducting unethical clinical trials.

On 8 October, the Supreme Court had made all states party in a public interest litigation (PIL), filed by
activist Swasthya Adhikar Manch, alleging serious irregularities in clinical trials in India. The case
specifically involved irregularities in trials at MGMC.

While Ramgulam Razdan, a psychiatrist at the hospital, has been transferred, the rest of the doctors are likely
to be suspended, said an official in chief minister Shivraj Singh Chauhan’s office who didn’t want to be
identified.

The chief minister had initiated departmental inquiry against four psychiatrists—V.S. Pal, Pali Rastogi, Abhay
Paliwal and Ujwal Sardesai—former dean Ashoka Vajpayee, current dean Pushpa Verma, professor of medicine Anil
Bharani, hospital superintendent Salil Bhargava, paediatrician Hemant Jain and neurologist Apoorv Puranik on 17
February.

According to documents submitted in the apex court, the psychiatrists had enrolled 233 mentally ill
patients in clinical trials without informed consent.

The state government has issued a show-cause notice to former dean Vajpayee for approving trials to be
conducted in MGMC without following the requisite procedures.

According to documents presented in the Rajya Sabha, 2,163 people have died in India due to clinical trials
since 2007 and 32 of these deaths occurred at MGMC.

Despite mounting evidence and various reports recommending criminal proceeding against the accused
doctors, the matter had been gathering dust for seven months, according to the petitioners in the PIL.
 The state’s new education minister Anoop Misra has indicated that erring doctors may be suspended,
said Chinmay Mishra, convener, Swasthya Adhikar Manch. “The state machinery will finally be taking
concrete steps after years of dilly-dallying because of the Supreme Court’s directions. We are expecting
transfers and suspension orders to be handed to the doctors. Various reports have already indicated that
these doctors should lose their practising licences; but we will have to see how serious the state government
is about setting standards for clinical trials.”

In June 2011, the Madhya Pradesh economic offences wing submitted a report on clinical trials at Maharaja
Yashwantrao Hospital and MGMC that established a conflict of interest, pointing out that pharmaceutical
companies had sent principal investigators in several trials on “foreign trips and money was received (by
the doctors)”.

A charge-sheet was filed by the Madhya Pradesh government in April this year but no action was taken
despite the chief minister ordering a departmental enquiry.

Besides this, the economic offences wing and a joint secretary in the state government had already
submitted reports, recommending action, including criminal proceedings, against the erring doctors.

Earlier this month, the Supreme Court threatened the central government with a blanket ban on clinical
trials in the country if the health ministry and state governments did not furnish details of trials within
eight weeks.

A bench of justices R.M. Lodha and A.R. Dave directed the Union government to compile data regarding
serious adverse events, deaths during trials, and compensation given to families before the next hearing.

he recent reporting of controversial drug trials being conducted by doctors of the government medical college
and private practitioners on ‘mentally challenged’ patients in Indore has caused uproar.[5] It was alleged that
for more than two years, from 2008 to 2010, trials were conducted flouting ethics guidelines. The Madhya
Pradesh government levied a fine of Rs 5000 each on the doctors involved, and this was seen widely as being
paltry and insufficient punishment.[6] As details emerged, questions were raised about the role of
independent or commercial (as compared to institutional) ethics committees, improper documentation of
consent, vulnerability of research participants as well as the thorny issue of private practice (and in this case,
research in private clinics) by government doctors.

NEWS

Supreme court ruling brings clinical trials

to a halt in India
BY DINSA SACHAN15 OCTOBER 2013


NO COMMENTS
  Save Article


Pressure from campaign group precipitates action that puts 162 drug trials on ice

The fate of 162 global clinical trials hangs in the balance, as the top Indian court has asked the government to provide
more details on their approval process before they can proceed.

The trials, most of which involve new chemical entities (NCEs), were approved by the drug controller general of India
earlier this year. During the latest hearing on a petition filed in February last year by Indore-based health pressure
group, Health Right Forum, the supreme court allotted the government two weeks to provide details on the mechanism
adopted to approve the trials.

India is not a good place for Phase II and Phase III trials for such products because of the inadequacies in the system

Amulya Nidhi, coordinator of Health Right Forum, says: ‘Clinical trials of NCEs are being conducted without following
proper protocol, and companies are taking advantage of poor people.’ New chemical entities are drugs that have not yet
been approved for marketing and are in various phases of testing. Indian drug laws don’t allow Phase I trials of drugs
developed outside of India, but they permit concomitant Phase II and Phase III trials of such products.

Trials of NCEs have fired controversy in India because of the high number of deaths that have occurred in the last few
years. According to information from the health ministry, 1542 deaths were reported in clinical trials between 2010 and
2012. However, only 54 of these were attributed directly to the trials.

Who benefits?

Commenting on the latest court order, C M Gulhati, editor of Monthly Index of Medical Specialities, India, says: ‘It is a
good interim order pending final disposal of the case. Testing of NCEs in India does not help the country. It only helps
multinational corporations to cut costs and avoid payment of compensation.’

Chinu Srinivasan, of Gujarat-based Low Cost Standard Therapeutics, a non-profit, small-scale pharmaceutical maker
and public health advocacy group, agrees. ‘India is not a good place for Phase II and Phase III trials for such products
because of the inadequacies in the system,’ he says. ‘The ancillary health services are weak. This is not Australia. If a
person in a clinical trial in a remote village gets a cardiac arrest, he can’t be immediately flown in to the nearest
hospital.’ Srinivasan adds that India is an attractive market for companies because the regulatory framework is weaker.

Recent amendments to India’s clinical research laws have led to the US National Institutes of Health pulling out of
clinical trials in the country. The amendments tighten rules on compensation and the registration of ethics committees.

Big business

According to market research firm Frost & Sullivan, the Indian clinical trial industry was worth $450 million (£282
million) in 2010–11. Presently it is growing at 12% a year and is predicted to pass the $1 billion mark in 2016. However,
recent developments have derailed progress. R K Sanghavi, head of the medical subcommittee of the Indian Drug
Manufacturers Association, says: ‘To be honest, the clinical trial industry in India is in shutdown mode.’

Suneela Thatte, president of the Indian Society for Clinical Research, says that clinical trials are essential for improving
the nation’s health. ‘The disease burden of India is like a double-edged sword,’ she says. ‘On one hand, we have a huge
burden of diseases common in the third world, such as tuberculosis and malaria. On the other hand, we are seeing a
sharp rise in diseases of the developed countries, such as diabetes, hypertension and psychiatric illnesses.’ Nidhi says
that the loss incurred by pharma companies is immaterial. ‘We are concerned about and committed to the interests of
people,’ he says. But Thatte reckons there is more to clinical trials than just profit making. ‘Clinical trials are the only
 hope for seriously ill patients who have tried all treatments without avail. By stopping trials, we’re denying them access
to new treatment opportunities,’ she laments.

Trials on trial

Recently, a committee headed by leading pharmacologist Ranjit Roy Chaudhurysubmitted a report recommending
ironing out the process of approving and conducting clinical trials. The committee was set up by the government
following the supreme court’s harsh criticisNEWS

Supreme court ruling brings clinical trials

to a halt in India
BY DINSA SACHAN15 OCTOBER 2013


NO COMMENTS

 Save Article


Pressure from campaign group precipitates action that puts 162 drug trials on ice

The fate of 162 global clinical trials hangs in the balance, as the top Indian court has asked the government to provide
more details on their approval process before they can proceed.

The trials, most of which involve new chemical entities (NCEs), were approved by the drug controller general of India
earlier this year. During the latest hearing on a petition filed in February last year by Indore-based health pressure
group, Health Right Forum, the supreme court allotted the government two weeks to provide details on the mechanism
adopted to approve the trials.

India is not a good place for Phase II and Phase III trials for such products because of the inadequacies in the system

Amulya Nidhi, coordinator of Health Right Forum, says: ‘Clinical trials of NCEs are being conducted without following
proper protocol, and companies are taking advantage of poor people.’ New chemical entities are drugs that have not yet
been approved for marketing and are in various phases of testing. Indian drug laws don’t allow Phase I trials of drugs
developed outside of India, but they permit concomitant Phase II and Phase III trials of such products.

Trials of NCEs have fired controversy in India because of the high number of deaths that have occurred in the last few
years. According to information from the health ministry, 1542 deaths were reported in clinical trials between 2010 and
2012. However, only 54 of these were attributed directly to the trials.
Who benefits?

Commenting on the latest court order, C M Gulhati, editor of Monthly Index of Medical Specialities, India, says: ‘It is a
good interim order pending final disposal of the case. Testing of NCEs in India does not help the country. It only helps
multinational corporations to cut costs and avoid payment of compensation.’

Chinu Srinivasan, of Gujarat-based Low Cost Standard Therapeutics, a non-profit, small-scale pharmaceutical maker
and public health advocacy group, agrees. ‘India is not a good place for Phase II and Phase III trials for such products
because of the inadequacies in the system,’ he says. ‘The ancillary health services are weak. This is not Australia. If a
person in a clinical trial in a remote village gets a cardiac arrest, he can’t be immediately flown in to the nearest
hospital.’ Srinivasan adds that India is an attractive market for companies because the regulatory framework is weaker.

Recent amendments to India’s clinical research laws have led to the US National Institutes of Health pulling out of
clinical trials in the country. The amendments tighten rules on compensation and the registration of ethics committees.

Big business

According to market research firm Frost & Sullivan, the Indian clinical trial industry was worth $450 million (£282
million) in 2010–11. Presently it is growing at 12% a year and is predicted to pass the $1 billion mark in 2016. However,
recent developments have derailed progress. R K Sanghavi, head of the medical subcommittee of the Indian Drug
Manufacturers Association, says: ‘To be honest, the clinical trial industry in India is in shutdown mode.’

Suneela Thatte, president of the Indian Society for Clinical Research, says that clinical trials are essential for improving
the nation’s health. ‘The disease burden of India is like a double-edged sword,’ she says. ‘On one hand, we have a huge
burden of diseases common in the third world, such as tuberculosis and malaria. On the other hand, we are seeing a
sharp rise in diseases of the developed countries, such as diabetes, hypertension and psychiatric illnesses.’ Nidhi says
that the loss incurred by pharma companies is immaterial. ‘We are concerned about and committed to the interests of
people,’ he says. But Thatte reckons there is more to clinical trials than just profit making. ‘Clinical trials are the only
hope for seriously ill patients who have tried all treatments without avail. By stopping trials, we’re denying them access
to new treatment opportunities,’ she laments.

Trials on trial

Recently, a committee headed by leading pharmacologist Ranjit Roy Chaudhurysubmitted a report recommending
ironing out the process of approving and conducting clinical trials. The committee was set up by the government
following the supreme court’s harsh criticism of the government’s lax approach to dealing with unethical trials.

The panel recommended that clinical trials only be conducted at centres that have been accredited. It also suggested that
the principal investigator of the trial, as well as the ethics committee of the institute, must be accredited. Among other
things, the committee noted that if a trial volunteer developed medical complications during a clinical trial ‘the sponsor
investigator’ will be responsible for providing medical treatment and care.

Srinivasan believes that while it’s a step forward, the report seems to favour multinationals, particularly by making it
easier for them to perform concomitant trials of NCEs discovered abroad. Gulhati points out another problem. ‘Ranjit
Roy Chaudhury has a clear conflict of interest since he is the head of clinical trial unit of Apollo Hospital, which is one of
the biggest private sector clinical site management organisations. It was wrong on the part of the government to appoint
a person who will benefit from changes in the rules,’ he says.

m of the government’s lax approach to dealing with unethical trials.

The panel recommended that clinical trials only be conducted at centres that have been accredited. It also suggested that
the principal investigator of the trial, as well as the ethics committee of the institute, must be accredited. Among other
things, the committee noted that if a trial volunteer developed medical complications during a clinical trial ‘the sponsor
investigator’ will be responsible for providing medical treatment and care.

Srinivasan believes that while it’s a step forward, the report seems to favour multinationals, particularly by making it
easier for them to perform concomitant trials of NCEs discovered abroad. Gulhati points out another problem. ‘Ranjit
Roy Chaudhury has a clear conflict of interest since he is the head of clinical trial unit of Apollo Hospital, which is one of
 the biggest private sector clinical site management organisations. It was wrong on the part of the government to appoint
a person who will benefit from changes in the rules,’ he says.

In 2009, a prominent international NGO had launched a $3.6 million human papillomavirus (HPV) trial in India
and tested two vaccines on 16,000 tribal girls in Andhra Pradesh and Gujarat, apparently without informed consent
from the girls’ parents.

Indians as guinea pigs

In 2005, an important change in the Drugs and the Cosmetics Act allowed concomitant phase II trials — the
stage where efficacy and safety of an experimental drug is tested — for the first time in India. It allowed
drugs discovered abroad by multinational pharmaceutical companies to be tested on Indians, without the
results coming in from the tests abroad. But clinical trials in India have been accompanied by large-scale
criminality as doctors, officials and pharmaceutical companies understand well enough that India is a
cesspool of corruption where clearances can be had for a pittance. While there have been many cases since,
the underbelly of India’s clinical trial industry came to the spotlight in 2005 when 3,300 patients were
subjected to 90 clinical trials that followed no protocols at a hospital in Indore, Madhya Pradesh. In American
law, such violations automatically attract the criminal charge of battery. In India, the poor don’t count at all.

Clinical trials ought to be done under calibrated statutory regimes where — among other things — there is
full disclosure to the patient undergoing the trial, the right to withdraw at any stage without any consequence,
comprehensive medical insurance, meticulous monitoring after administration of the drug for serious adverse
effects, and free access to the drug for the trial participants when it is cleared for commercial use. Despite
several crimes of enormous proportion where the poor are tested as guinea pigs, nothing has ever been done.
The patients continue to die or suffer severe adverse effects, monitoring is never done, compensation is
seldom paid, medical treatment is seldom provided and prosecutions are the exceptions to the rule.

A home to more than one billion people, India is a land of vast human diversity, consisting of more than four and a
half thousand anthropologically well-defined populations. Each population differs in terms of language, culture, customs,
physical features and genetic architecture, which is determined by DNA— the hereditary material that is passed on from
one generation to the next. Thanks to CSIR-Centre for Cellular and Molecular Biology (CCMB) scientists, who in
collaboration with scientists from Harvard Medical School, USA have provided us the genetic evidence for the origin and
affinities of Indian populations.

SOP -STANDARD OPERATING PROCEDUREthe FDA does not regulate whether the PI has to be a MD.
How about Good Clinical Practice? GCP does seem to suggest a higher standard. Although not specifically requiring a
medical degree, GCP talks about medical decisions and qualified physicians.

 ICH GCP 4.1.1: The investigator should be qualified by education, training and experience to assume responsibility for the
proper conduct of the trial.
 ICH GCP 2.7: The medical care given to, and medical decisions made on behalf of, subjects should always be the
responsibility of a qualified physician or, when appropriate, of a qualified dentist.
 ICH GCP 4.3.1: A qualified physician, who is an investigator or a sub-investigator for the trial, should be responsible for all
trial-related medical decisions.

Since investigator selection is the responsibility of the Sponsor, it is ultimately their decision. However, it is dependent on
the type of study. Typically for IND studies, if the PI is a non-MD there is a MD listed on the 1572 to perform any medical
decisions (diagnosis, distribution of medication). If the device study is an implantable device, the PI will always be a
surgeon with experience in the study indication. But, if the device is non-implantable and let’s say is used for physical
therapy patients with neck pain- the PI may be a DPT or PhD as the PI would be qualified by education, training and
experience.
We would love to hear your thoughts. Have you ever had a Sponsor not allow a non-physician serve as the PI? Have you had
a non-physician PI and medical oversight from a sub-investigator?
Photo Credit: Horia Varlan

Topics: Good Clinical Practice, Investigator Qualifications, FDA

Ethics Committee Accreditation and Registration in India :

A Short Online Course
There are around 1200 registered independent and institutional ethics
committees. All registered ethics committees have to go through
accreditation process which was introduced recently by NABH and
responsibility is assigned to quality council of India (QCI) to accredit all
registered ethics committees in India. The ethics committee should review
and accord its approval to a clinical trial as per Schedule Y, the Good
Clinical Practice Guidelines for Clinical Trials in India and other applicable
regulatory requirements for safeguarding rights, safety and well-being of
the trial subjects.

The applications of registration of Ethics Committee have to be mandatorily

filed online by www.cdscoonline.gov.in.
http://www.cdsco.nic.in/writereaddata/NOTICE-%20COSECR.pdf

Accreditation of Ethics Committees involved in supervision of clinical trials

is mandatory with effect from 01.01.2018 and before that accreditation will
be voluntary. Ministry has approved accreditation of Ethics Committee for
Clinical trials. NABH has now started accepting application for Accreditation
of Ethics Committee program with refer to letter no. QCI/NABH/CDSCO/15.

http://www.nabh.co/Announcement/Accreditation_ECApproval.pdf

Draft Standards And Application Format For Accreditation Of Ethics

Committee, Investigator And Clinical Trial Site
http://www.cdsco.nic.in/Forms/list.aspx?lid=2074&Id=23
 Keeping in view the registration and accreditation requirement of Ethics
Committee, this course has been framed to provide a basic understanding
about the functioning and responsibility of Ethics Committee. Further this
course will also be helpful to all stakeholders involved in clinical trial to
comply with the necessary requirements and application process of
accreditation with NABH & Registration with CDSCO.

This brief e-course covers the accreditation process of NABH along with
registration process of IEC with CDSCO.

This Course has following modules:

1. Regulation and Guidelines for Ethics Committee in India

2. Composition of Ethics Committee
3. Standard Operating Procedures of Ethics Committee
4. Functioning of Ethics Committee
5. Submission of Clinical Trial Dossier to Ethics Committee
6. Records Maintained by Ethics Committee
7. Review and Approval Process of Ethics Committee
8. Responsibility of Investigator Towards Ethics Committee
9. Registration of Ethics Committee with CDSCO
10. Accreditation of Ethics Committee by NABH

Fill the form to register for the course :

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Auriga Research Pvt. Ltd. (A Contract Research Organization)

3/15 Kirti Nagar Industrial Area
New Delhi
India 110015
e-mail - auriga@aurigaresearch.com
Telephone - +91-11-45754575
COPYRIGHT © 2017 AURIGA RESEARCH PV

Although the category is called "exempt," this type of research does require IRB review and registration.
The exempt registration process is much less rigorous than an expedited or full-committee review. To qualify, research
must fall into six (6) federally-defined exempt categories.

OHRP Expedited Review Categories (1998) Research activities that (1) present no more than minimal risk to human
subjects, and (2) involve only procedures listed in one or more of the following categories, may be reviewed by
the IRB through theexpedited review procedure authorized by 45 CFR 46.110 and 21 CFR 56.110.

45 CFR 46.110 - Expedited review procedures for certain kinds of

research involving no more than minimal risk, and for minor
changes in approved research.
 eCFR
 Authorities (U.S. Code)
 Rulemaking
 What Cites Me
prev | next
§ 46.110 Expedited review procedures for certain kinds of research involving
no more than minimal risk, and for minor changes in approved research.

(a) The Secretary, HHS, has established, and published as a Notice in the FEDERAL REGISTER, a list of
categories of research that may be reviewed by the IRB through an expedited review procedure. The list
will be amended, as appropriate after consultation with other departments and agencies, through
periodic republication by the Secretary, HHS, in the FEDERAL REGISTER. A copy of the list is available from
the Office for Human Research Protections, HHS, or any successor office.
(b) An IRB may use the expedited review procedure to review either or both of the following:
(1) Some or all of the research appearing on the list and found by the reviewer(s) to involve no more
thanminimal risk,
(2) Minor changes in previously approved research during the period (of one year or less) for which
approval is authorized.
Under an expedited review procedure, the review may be carried out by the IRB chairperson or by one
or more experienced reviewers designated by the chairperson from among members of the IRB. In
reviewing the research, the reviewers may exercise all of the authorities of the IRB except that the
reviewers may not disapprove the research. A research activity may be disapproved only after review in
accordance with the non-expedited procedure set forth in § 46.108(b).

(c) Each IRB which uses an expedited review procedure shall adopt a method for keeping all members
advised of research proposals which have been approved under the procedure.
(d) The department or agency head may restrict, suspend, terminate, or choose not to authorize
aninstitution's or IRB's use of the expedited review procedure.
[ 56 FR 28012, 28022, June 18, 1991, as amended at 70 FR 36328, June 23, 2005]

Vulnerable populations include the economically disadvantaged, racial and ethnic minorities, the uninsured, low-
income children, the elderly, the homeless, those with human immunodeficiency virus (HIV), and those with other
chronic health conditions, including severe mental illness.Nov 1, 2006

Phase Aim Notes

Phase 0 trials are optional first-in-human trials. Single subtherapeutic doses

of the study drug or treatment are given to a small number of subjects (10 to
15) to gather preliminary data on the agent's pharmacodynamics (what the
Phase Pharmacodynamicsand pharmacokinetics in
drug does to the body) and pharmacokinetics (what the body does to the
0 humans
drugs).[33] For a test drug, the trial documents the absorption, distribution,
metabolization, and removal (excretion) of the drug, and the drug's
interactions within the body, to confirm that these appear to be as expected.

Often the first-in-man trials. Testing within a small group of people (20–80)
to evaluate safety, determine safe dosage ranges, and begin to identify side
Phase
Screening for safety effects. A drug's side effects could be subtle or long term, or may only
1
happen with a few people, so phase 1 trials are not expected to identify all
side effects.

Testing with a larger group of people (100–300) to determine efficacy and to

Phase Establishing the efficacy of the drug, usually
further evaluate its safety. The gradual increase in test group size allows for
2 against a placebo
the evocation of less-common side effects.
 Testing with large groups of people (1,000–3,000) to confirm its efficacy,
Phase
Final confirmation of safety and efficacy evaluate its effectiveness, monitor side effects, compare it to commonly used
3
treatments, and collect information that will allow it to be used safely.

Postmarketing studies delineate additional information, including the

Phase treatment's risks, benefits, and optimal use. As such, they are ongoing during
Safety studies during sales
4 the drug's lifetime of active medical use. (Particularly after approval
under FDA Accelerated Approval Program)

Trial design[edit]

Contract research organizations (CROs) provide clinical trial and other research support services for the
pharmaceutical, biotechnology, medical device industries and also serve government institutions, foundations, and
universities.

In the changing economy, pharmaceutical companies are increasingly looking to outsource critical functions, including
manufacturing and research. More and more of the major corporations are using CROs to lead clinical trials and develop
new medications.

What is a Contract Research Organization?

A CRO is an organization contracted by another company to manage and lead the company's trials, duties, and functions.

Organizations and businesses that contract with CROs do so to acquire specific expertise without hiring permanent staff.
CRO trade groups claim that when firms or public entities outsource to a CRO, it reduces the time it takes to conduct a trial
versus doing the trial in-house, and that translates to significant cost savings. A contract with an outside company means that
the hiring organization does not need the infrastructure, office space or manpower to run these trials themselves.

Some CROs manage almost all aspects of a clinical trial, from site selection and patient enrollment through final regulatory
approval from the Food and Drug Administration and European Medicines Agency.

Although a trial sponsor may transfer all trial functions to a third-party CRO, the sponsor remains responsible for the
integrity of the trial data and to ensure it is all factual and backed by good science.

Types of Services Provided by CROs

Contract research organizations offer comprehensive services, including:

 Project management
 Database design & build

A Growing Sector, CROs Play a Major Role in Drug Development. Contract research organizations (CROs)
provide clinical trial and other research support services for the pharmaceutical, biotechnology, medical device
industries and also serve government institutions, foundations, and universities. Feb 19, 2017
Who’s in Charge at the Study Site? s in Charge at the Study Site? Clinical investigators are in charge
and held accountable – FDA regulations permit sponsors to delegate their responsibilities to
Contract Research Organizations (CROs) but do not permit clinical investigators to delegate their
general responsibilities to CROs or site management organizations, subinvestigators, or study staff
Penalties for significant noncompliance – Warning Letters (posted on FDA website) –
Disqualifications/Restrictions/Debarments (posted on FDA website) – Criminal
prosecutions/prison/fines

Informed consent is a process that includes all of these steps:

 You are told (or get information in some way) about the possible risks and benefits of the
treatment.

 You are told about the risks and benefits of other options, including not getting treatment.

 You have the chance to ask questions and get them answered to your satisfaction.

 You have had time (if needed) to discuss the plan with family or advisors.

 You are able to use the information to make a decision that you think is in your own best interest.

 You share your decision with your doctor or treatment team.

If you have gone through these steps and decide to get the treatment or procedure, you are usually asked
to sign a paper called a consent form. The completed and signed consent form is a legal document that lets
your doctor go ahead with the treatment plan. The consent form names the procedure or treatment to be
done. The rest of the form may be very general, stating only that you have been told about the risks of the
treatment and other available options. Or it may be very detailed, outlining what the risks and other options
are. Depending on how it’s presented, you may sign for one certain procedure or treatment, or you may
give approval for any treatments and procedures that the health provider decides are needed.

From the doctor’s viewpoint, informed consent means that:

 A doctor or nurse must make every effort to be sure the patient understands the purpose, benefits,
risks, and other options of the test or treatment. Then the doctor or nurse must get the patient’s
consent before starting. In some cases, even a simple blood test or an injection (“shot”) requires
written consent from the patient.

 As long as adult patients are mentally able to make their own decisions, medical care cannot begin
unless they give informed consent.

 If the patient is a minor (under age), has a serious mental disability, or cannot give consent, then
the parent, legal guardian, or a person authorized by the court must give consent before treatment
can start. This is usually a close family member who has reason to know what the patient would
want. (See “Who besides the patient can give consent?” in the section “What are the legal
requirements of informed consent?”) As some very public court cases have shown, an elaborate
legal system is in place to guide cases in which the patient is mentally or physically unable to give
 informed consent for treatment. These cases tend to come up when the patient is in a coma
(unconscious) or on life support.

Sometimes health care workers refer to the consent form itself as an “informed consent.” This is not quite
accurate. Informed consent is the process and actions that take place as you learn about and think about a
treatment before you agree to it. Your signature on the form is taken to be evidence that this took place. If
you decide that you don’t want the procedure or treatment, you should not sign the consent form. In this
case, you may be asked to sign an informed refusal form or a form that states you are choosing not to
follow medical advice. Your signature on this form implies that you know the risks of refusing, so be sure
that you understand these risks and know your other options before you sign. (See the section called “What
if I don’t want the treatment being offered?”)

 Written by

How is informed consent for a clinical

trial or research study different from
consent for standard treatment?
Informed consent for a clinical trial or investigational drug or procedure (where new treatments are
compared to the current standard treatment) usually includes more information than the consent for
standard treatment. The informed consent process should tell you:

 What the clinical trial is set up to find out

 What is expected of you – what will be done and how long you will take part

 Expected benefits

 What’s known and not known about the new drug or procedure

 Any possible risks to you (if known)

 Whom you should contact with questions about or problems with the study

 Other possible treatment options

 That you can leave the study with no penalty and opt for standard medical care at any time

 How your personal information will be protected

The informed consent process is meant to give you ongoing explanations that will help you make educated
decisions about whether to start or stay in a clinical trial. The most important part of this process is your
everyday interaction and discussions with the research team and other medical staff before, during, and
after the trial. The consent form can be a great tool to help get this conversation started.

This is all done so that you can make the best decision for yourself, and to be sure that you are able to
choose freely whether to enroll in or stay in the study. Much of this information may be on the consent form
itself, which also usually explains that you can withdraw from the study at any time without penalty. The
doctor or nurse may encourage you to take extra time to think it over and come back with any questions. If
you are giving consent for your child, both parents may be required to sign the form in order for the child to
take part in the clinical trial.

Before you decide, the research team will talk with you about the clinical trial’s purpose, procedures, risks,
possible benefits, and your rights as a participant. If you decide to take part, the team will keep you up to
date on any new information that may affect you and your situation. Before, during, and even after the
clinical trial, you will have the chance to ask questions and talk about your concerns. Informed consent for
clinical trials goes on for as long as the research lasts, and even afterward.

The process varies among different research institutions and clinical centers, but normally informed
consent for a clinical trial includes these steps:

A first meeting. This is when you meet with a member of the research team who gives
you the informed consent document and explains it to you. This discussion may also
include your oncologist (cancer specialist), primary care doctor, and a nurse. Sometimes
a social worker, patient representative, or staff psychologist may be there, too. You can
bring along a family member or friend for support, and to help you keep track of the
information. The information should be given in a way you can understand. It should also
be given at a comfortable pace, with time allowed for you to think it over and ask
questions. Some centers offer a video, audio recording, or an interactive computer
module to help you better understand the information in the consent form.

Time to take in the information. It can be hard to absorb so much new information in
one sitting, espe

Who besides the patient is allowed to

consent?
For children or others who are unable to make the decision for themselves, the parent or legal guardian is
legally responsible for getting the information, making the decision, and signing the consent form. But that
doesn’t mean that the child or patient who is not considered mentally competent is always left out of the
process. Some facilities require the assent of older children before they go into a research study, even after
the parents have agreed on the child’s behalf. Assent means that, even though the parents sign the form,
the child must also be OK with the plan before the facility will do the treatment.

Along the same lines, people who are unable to manage their daily affairs because of impaired thinking or
emotional problems might still be able to understand the medical situation and make their wishes known.
They should be given information in a way they can understand, and asked what they want to do.

In the event that you become unable to take in information and make your wishes known, another person
may be asked to take part in the process of informed consent. There are several ways that person can be
chosen.

Durable power of attorney for health care

The only way you can choose the person to make these decisions for you is to set up a durable power of
attorney for health care (also called a health care power of attorney). In this case, if you are unable to
speak for yourself, the person you chose becomes legally responsible for making medical decisions on
your behalf. This person is sometimes called your proxy, agent, or surrogate. For more on health care
powers of attorney, see our information, Advance Directives. (You can read it on our website, or call us for
a copy.)

Court-appointed proxy
Another option is a court-appointed surrogate or proxy. This is someone a judge chooses to make medical
decisions for you. If you become unable to make decisions for yourself, someone else – such as the doctor,
facility, a friend, or a family member – m

A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who
attends the informed consent process if the subject or the subject's legally acceptable representative cannot read, and
who reads the informed consent form and any other written information supplied to ...

Query on Legally Acceptable Representative

and Impartial Witness
(04/06/2010)

Question 1:

I have a query regarding Legally Acceptable Representative (LAR) and Impartial Witness (IW). The question and my reasoning
for the question is mentioned below.

Question- Can LAR act or play a role of impartial witness?

Reason- I think LAR can play a role of impartial witness.

When patient is illiterate then as per GCP we require an individual independent of trial to assure that consent process was
conducted explaining all the information mentioned in the Informed consent documents to patient. We just want to ensure that
no advantage of the illiteracy of the patient is taken by investigator while performing Informed consent process. So we ensure
it by keeping a person who has no link with investigator or site staff or site to just witness the informed consent process. This
requirement is fulfilled by impartial witness.

Now LAR is used when patient is minor, unconscious or not capable / eligible to give consent to participate in trial. Now LAR
gives consent on behalf of patient to participate in trials.

My point is if we allow LAR to give consent on behalf of the patient when patient can not, then why in illiterate patient we
should not consider or count LAR's presence in Informed consent procedures to witness and declare that all the content of
informed consent documents were explained to patient.

How LAR can be bias while acting as a witness to ICF procedures, and if LAR can be bias then how we can allow him to consent
on behalf of patient.

Why is it that LAR can give consent on behalf of patient but can not stand in ICF as a witness to guaranty the ICF process? One
can say that because LAR is not impartial but that's not all, why his presence should not be counted to perform a role of IW.

Please try to understand and then answer my query. I have asked it to many clinical trial professionals and to my colleagues
but what answer I get is definitions of all the terms and guideline statements of when to use LAR and impartial witness. I
expect strong reasoning to do certain thing or to not to do certain thing. Please reply or show me the way where to ask my
query.

Answer 1:

Under FDA's regulations, the legally authorized representative (LAR) and the impartial witness (IW) perform different roles in
the informed consent process and if both are required in a given situation, then different individuals would need to fulfill these
roles.

If a patient is illiterate but can provide consent, then only an IW is needed. An LAR would not be needed just because the
patient is illiterate. If the patient cannot provide consent, then an LAR would be needed but an IW would not be needed unless
the LAR was also illiterate, in which c

Objectives ◦ Review the basic process of obtaining informed consent ◦ Describe how to
obtain consent through fax or email ◦ Distinguish when it is appropriate to use a legally
authorized representative (LAR) ◦ Detail how to obtain consent from illiterate or blind
subjects ◦ Cover the documentation of consent in other languages (translated consents, short
forms) ◦ Review commonly observed mistakes in the consent process 2 ICF= Process +
Documentation ◦ More than just a signature on a form ◦ Process of information exchange that
may include: ◦ Subject recruitment materials ◦ Verbal instructions ◦ Reading and signing the
ICF ◦ Q+A sessions and measures of subject understanding ◦ Documentation that the consent
process has been handled correctly is crucial Who Handlease both an LAR and IW would be needed.

Who Handles the Consent Process? ◦ Person should be trained regarding informed consent process
and be knowledgeable about study ◦ FDA Requirements: IRB must know who will conduct consent
process ◦ FDA does not require the that the PI personally conduct the consent process, but the PI is
always responsible for ensuring that the process is completed correctly ◦ Study team should verify
who can conduct the consent discussion with the sponsor and staff members who will obtain
consent should be listed on the delegation of authoConsent Discussion ◦ An approved study team
member should review the form with the subject and have a conversation about the study ◦ The
conversation should allow for the subject to ask any questions he or she may have and for the
researcher to assess the subject’s level of understanding ◦ The study team should take the time to
ensure the subject understands all aspects of the study thoroughly, even if the subject claims to
have read the document prior to the discussion rity l

Provide the subject a copy of the form to keep for reference ◦ The form has contact information in it
in case the subject has any questions later ◦ If the study is following ICH-GCP, make sure the subject
receives a signed copy of the ICF

How to obtain consent through fax or email o First, make sure this method was approved by the IRB
o Send the ICF to the subject through the IRB-approved method o Carry out the consent process by
phone while the subject or representative reads along o After the discussion, the subject or
representative can sign the form and return it to investigators via fax, through secure email, or by
posting it to a secure website o “Secure” means HIPAA-c

How to obtain consent through fax or email o The subject may also bring the signed and dated
consent form to the next study visit or mail it to the investigator o Be sure that the person obtaining
consent signs and dates at the time the returned form is truly received o Any delays should be
explained in the Consent Process Note. Do not provide a date or a time that is inaccurateHow to
obtain consent through fax or email with minor subjects 12 ◦ Use the same procedure to obtain
consent from the parent or legal guardian and assent from the minor subject ◦ Be sure to document
assent based on age-based guidelines, or IRB requirements ◦ If the only contact with subjects is
completed remotely, please contact the IRB to decide how to appropriately verify the identity of the
parent or guardian providing consent for the minor subject’s participation Suggestion for
documenting

Illiterate or blind subjects ◦ The PI should read the entire consent or assent document aloud and
document that the subject cannot read ◦ An impartial individual should witness the process and
document that the process took place, that the subject understands, and the subject consented to
participate

Commonly Observed Errors in Consent Documentation ◦ Faxed/Emailed forms: wrong date or time is
used to match subject’s signature ◦ Person obtaining consent signs before subject ◦ Person obtaining
consent dates and times subject’s signature ◦ Corrections made inappropriately ◦ Consents
faxed/emailed when the study wasn’t approved for that process 23

Commonly Observed Errors in Consent Documentation ◦ Fields left blank in the ICF ◦ The
original document cannot be located, only a copy exists ◦ Unapproved study staff performing
informed consent discussion ◦ No consent process note or note to file regarding irregularities

Some examples of situations that might warrant re-consent include:

 ▶ Failing to inform the subject about important risks related to the study.

 ▶ Conducting the consent when the subject’s decision-making capacity was compromised or the subject was
under duressSignificant changes in the research procedures, risks, potential benefits, or alternatives.
 ▶ The subject’s medical condition worsens or does not respond to treatment.8
 ▶ Research in which paediatric subjects will reach adulthood while the study is still in progress, such as a
longitudinal, prospective cohort study that follows children from birth through adulthoo
 Significant changes in the research procedures, risks, potential benefits, or alternatives.
 ▶ The subject’s medical condition worsens or does not respond to treatment.8
 ▶ Research in which paediatric subjects will reach adulthood while the study is still in progress, such
as a longitudinal, prospective cohort study that follows children from birth through adulthoo

 .

Duplicate publication, multiple publication, or redundant publication refers to publishing the same intellectual material more than
once, by the author or publisher. It does not refer to the unauthorized republication by someone else, which
constitutes plagiarism, copyright violation, or both.

"stealing and publication" of another author's "language, thoughts, ideas, or

Pliagarism;
expressions" and the representation of them as one's own original work. ... Recently,
cases of 'extreme plagiarism' have been identified in academia.
Multiple submission is not plagiarism, but it is today often viewed as academic misbehavior[
 High- Altitude

Experiment Mustard Gas

Experiment