After more than
two years since the registration of clinical trials was made mandatory in the
country, the Union health ministry will soon make the registration of
bioavailability and bioequivalance (BA/BE) studies mandatory with the Clinical
Trial Registry of India (CTRI).
According to sources, the Union health ministry has already taken the decision
in-principle to make the registration of BA/BE studies mandatory, on the same
lines of the other clinical trials in the country. The drugs controller general
of India (DCGI) Dr Surinder Singh has already directed the senior officials in
the CTRI to make the necessary changes in its web network to incorporate the
BA/BE features, sources said.
According to sources, just like the clinical trials, the DCGI wanted to streamline
the BA/BE studies in the country. So far, registration of BA/BE studies with
the CTRI was optional. Once the DCGI makes it mandatory, all the BA/BE studies
have to be registered with the CRTI without which the DCGI wil…
The most costly part of new drug discovery is the three phase clinical
research lasting for three to four years involving thousands of human
volunteers and investigators in multi locations. Any of these potential
drug candidates can be abandoned during the trial period if their
adverse drug events are beyond the acceptable limits.
It is certainly a
high risk activity involving millions of dollars and pharmaceutical
companies usually make sure that trial reports reaching the regulatory
authorities are favourable. No new drug can be approved for marketing
without submission of trial reports and their scrutiny by the regulatory
authorities. Because of these reasons, the whole operation of clinical
research is highly secretive.
Apart from top MNCs like Pfizer, GSK,
Novartis and Novo Nordisk, there are a large number of contract research
organizations engaged in clinical trials in India for the last ten
India will soon quantify the amount of compensation to be paid by
pharmaceutical companies, if a volunteer dies or gets injured during a clinical
trial. On October 10,
the Drug Technical Advisory Board (DTAB) gave its nod to the Central Drugs
Standard Control Organization (CDSCO) to prepare a "compensation
chart" or extensive guidelines that will specify the amount to be paid. Ethical
committees of the company will have to decide the quantum of compensation on
the basis of these guidelines. The
compensation has to be paid by the trial's sponsor or its representative within
90 days of the death or injury to the victim or the next of h/his kin. In the
first 30 days, the firm will have to prove to the ethics panel that the death
or injury wasn't due to the drug, else it has to pay. In India,
pharma companies pay compensation "according to their will" that
varies between Rs 1 lakh and Rs 10 lakhs since "no set parameters have
been laid down".
International is the only CRO in India to manage hemophilia trials according to
the Clinical Trials Registry-India (CTRI). Of the total hemophilia trials
currently being conducted in India, Max Neeman can boast supporting 80% of
these with the remaining conducted by pharma companies. Max Neeman
International has established a team of experts specialized in carrying out
hemophilia trials in response to sponsor demand. The team has the required
expertise via involvement of academia with industry, hemophilia trial
experience and extensive database of best Investigators for indication to
develop innovative approaches to optimize complex study design. Often strict
inclusion/exclusion criteria and data analysis for such studies create the
greatest challenge for Biotech and Pharma that the company's expertise can
BE guidelines recommend investigator should possess appropriate
medical qualification, experience for conducting pharmacokinetic studiesCan chairperson of EC directly write to sponsor to clarify some of the queries of clinical trial raised in EC meeting? Dr. Sreevatsa
Please see an extract from FDA's comment on IRB-sponsor relationship.
interrelationship and interaction between the research sponsor (e.g.,
drug, biologic and device manufacturers), the clinical investigator and
the Institutional Review Board (IRB) may be very complex. The
regulations do not prohibit direct sponsor-IRB contacts, although, the
sponsor-IRB interaction customarily occurs through the investigator who
conducts the clinical study.
The clinical investigator generally
provides the communication link between the IRB and the sponsor. Such
linkage is agreed to by the sponsors and investigators when they sign
forms FDA-1571 and FDA-1572, respectively, for drug and biologic studies
or an investigat…
How will we conclude that the subject is illiterate?
Dr Prakash Atlam
The guidelines don’t use the term illiterate. Their focus is subject’s ability to read and/or write.
Schedule Y treats anyone who is unable to read or write in the same way. See the excerpt below.
If the subject or his/her legally acceptable representative is
unable to read/write - an impartial witness should be present during the
entire informed consent process who must append his/her signatures to
the consent form.
While designing a protocol we found that there are high likely
chances of worsening of some of the symptoms. Do we have to wait for
these to happen and report it as SAE or in case we define them in the
protocol upfront then can we prevent from expediting reporting it as
Please see suggested guidance from ICH. Exemption from reporting
such events would require prior agreement with regulatory authorities.
ICH E3 12.2.2 Display of Adverse Events: All adverse events
occurring after in…
Can an Ethics Committee member e.g. layman/chairman or anyone in the committee participate in the trial as a subject?
If an Ethics Committee member becomes a trial subject on a trial
that he/she was involved in approving then there has been a major
conflict of interest. The following situations need to be considered:
● IEC member reviews study without any prior knowledge of the
study, votes, and then afterwards is approached by clinical research
team to participate. Possibly this is OK but the member should no longer
be part of the IEC that reviews that study. This will be difficult in
practice, so therefore it is not advisable.
● IEC member already knows about the study and is voting in order
to be able to participate. This is clearly not acceptable and made worse
if there is additional financial incentive for the study (e.g.
ICH GCP requires Ethics Committee members to be independent of the investigator and the sponsor to avoid conflicts of int…
Is it necessary to obtain DCGI/EC approval for clinical trial of
nutraceutical and register the trial in CTRI? Is it essential to carry
out toxicity studies? Binu Kuruvilla
DCGI approval is not required unless the indication claim is as per
definition of a new drug as per Drugs & Cosmetics Rules.
The definition of drug is as follows:
All medicines for internal or external use of human beings and all
substances intended to be used for or in the diagnosis, treatment,
mitigation or prevention of any disease or disorder in human beings.
In addition, you should consider new drug definition as per Rule 122E.
drug is considered a new drug if
1) it is a new chemical, biological
or recombinant bio-technological or such devices or delivery systems
drug already approved for certain claims is now being considered for
modified or new claims, namely, indications, dosage, dosage form
(including sustained release dosage form) and route of administration
fixed dose combinati…
Please clarify re: patient reported outcome (PRO) instruments: 1) Post translations whose responsibility is it to validate the translated version of the questionnaire? 2) Could the translated version be submitted to the regulatory authority without validation? 3) Whose responsibility is it to submit the translated questionnaire post validation? 4)
If any modification is done in the validated translated version then is
there a requirement to validate the modified version and then submit
the same to the regulatory authority? 5) What if a translated
questionnaire is used without validation considering a situation where
only English document has been submitted to the regulatory authorities
and the translated version have only been submitted to the respective
Ethics Committees?Garima SinghFor 1) & 3) -
FDA has released a guidance on PRO in Dec 2009. It is addressed to
sponsors. Hence, they are responsible for validation of the PRO
instrument - both English as well as translations.…
research is the key to the discovery of latest diagnostic methods and to
develop modern drugs for treatment of diseases. Good Clinical Practices
(GCP) is an ethical and scientific quality standard for designing,
conducting and recording trials that involve the participation of human
subjects. Compliance with this standard provides assurance to public
that the rights, safety and well being of trial subjects are protected,
consistent with the principles enshrined in the Declaration of Helsinki
and ensures that clinical trial data are credible. It
has been widely recognized that India offers unique opportunities for
conducting clinical trials in view of the large patient pool, well-
trained and enthusiastic investigators and premiere medical institutes
available in the country along with considerable low per patient trial
cost, as compared to developed countries. A
A trial patient visited the site
complaining breathlessness and tachycardia. The investigator advised
hospitalization but as subject could not afford the expenses, he refused
for admission. Is this an SAE because investigator advised
hospitalization?G Praveen Kumar.
the patient was not hospitalized, it does not fall into SAE criteria of
hospitalization. However, it appears from your mail that the PI felt
that the event was serious enough to admit the subject for treatment.
This makes it an “important medical event." As per ICH E2A such event
also are considered serious. See the ICH E2A excerpt below:
and scientific judgement should be exercised in deciding whether
expedited reporting is appropriate in other situations, such as
important medical events that may not be immediately life-threatening or
result in death or hospitalisation but may jeopardise the patient or
may require intervention to prevent one of the other outcomes listed in
the definition ab…
In order to cope up with the momentum in registration of clinical trials in the country which has been picking up fast ever since registration of clinical trials was made mandatory by the DCGI from June 15, 2009, the Union Health Ministry has upgraded the Clinical Trial Registry of India (CTRI) with several new features.
In the upgraded version, the CTRI has incorporated new features on audit trial, submission of EC-DCGI approval documents, trial transfer, trial search, etc.
In the new software application, once a trial is registered, all fields would be automatically 'locked' except for 'Recruitment status of trial'. In case changes are desired to be made, request has to be sent to the CTRI, quoting CTRI registration number, indicating the field that is to be changed. Accordingly, only the desired field will be 'unlocked' and once changes have been incorporated, the field will again become 'locked'. Further, all these changes will be avail…
Despite massive advertising and booming prescriptions, use and sales, the new atypical antipsychotic medications such as Seroquel and Abilify – used to treat schizophrenia, bipolar disorder, depression and other illnesses – lack sufficient evidence to support their widespread and generalized usage. This according to a new study out of the Stanford University School of Medicine and University of Chicago.
In the past decade, atypical antipsychotics have rocketed past many commonly prescribed, but older antidepressant and other psychiatric medications. Although initially touted as having few side effects, followup studies have found that atypical antipsychotics have serious side effects, including significant weight gain that can lead to diabetes and heart disease.
“Because these drugs have safety issues, physicians should prescribe them only when they are sure patients will get substantial benefits,” said Randall Stafford, M.D., Ph.D., a Stanford associate professor of medici…