Skip to main content

EC chairperson can serve as legal expert during the meeting

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 Singh
For 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.
For 2) - The FDA expects the sponsor to submit validated translations (see below appendix to the FDA guidance).
VIII. Language Translation and Cultural Adaptation
  • Process used to translate and culturally adapt the instrument for populations that will use them in the trial
  • Description of patient testing, language- or culture-specific concerns, and rationale for decisions made to create new versions.
  • Copies of translated or adapted versions
  • Evidence that content validity and other measurement properties are comparable between the original and new instruments
For 4) - If there is a modification, following documents are required.


  • Any change in the original instrument (e.g., wording of items, response options, recall period, use in a new population or indication)
  • Rationale for and process used to modify the instrument
  • Copy of original and new instruments
  • Evidence that content validity and other measurement properties are comparable between the original and modified instruments (including use in a new indication or population).
For 5) - It would be necessary to validate the translated instrument before using it in the patients. So even if it submitted/approved by EC, the validation is a must. Also, as per FDA guidance, the validated translation must be submitted to FDA.

Can EC chairperson act as legal expert during the meeting (dual role)? Please let me know if in this case, EC quorum met as per Schedule Y?
A. Mohammed Asif
The chairperson can serve as a legal expert. However, the person should be officially designated in the EC SOPs as legal expert for all meetings/quorum. The quorum requires the following EC members representing different roles
For review of each protocol the quorum of Ethics Committee should be at least 5 members with the following representations:
  • basic medical scientists (preferably one pharmacologist).
  • clinicians
  • legal expert
  • social scientist / representative of non-governmental voluntary agency / philosopher /  ethicist /  theologian or a similar person
  • lay person from the community.
 It does not give EC titles e.g. chairperson. Hence, a chairperson serving as a lawyer can fulfill the requirements of quorum.

Protocol requires that when study drug X+Y is to be administered, drug Y is supposed to be administered first, followed by a normal saline flush, then drug X to be administered. In one patient, drug X was administered first then Y. Is it a protocol deviation or violation?
Praveen
There is no official definition of protocol violation / deviation. However, some guidance is given below:

EFGCP Audit Working
Party 2001

Protocol Violation: Serious non-compliance - may lead to exclusion of patients from eligibility analysis and/or their discontinuation from the study
Protocol Deviation: Less serious non-compliance - may not render a patient ineligible
Norman M. Goldfarb J of Clinical Research Best Practices Nov 2005
  • Protocol Deviation. A protocol deviation occurs when, without significant consequences, the activities on a study diverge from the IRB-approved protocol, e.g., missing a visit window because the subject is travelling. Not as serious as a protocol violation.
  • Protocol Violation. A divergence from the protocol that materially (a) reduces the quality or completeness of the data, (b) makes the ICF inaccurate, or (c) impacts a subject’s safety, rights or welfare. Examples of protocol violations may include:
  • Inadequate or delinquent informed consent
  • Inclusion/exclusion criteria not met
  • Unreported SAEs
  • Improper breaking of the blind
  • Use of prohibited medication
  • Incorrect or missing tests
  • Mishandled samples
  • Multiple visits missed or outside permissible windows
  • Materially inadequate record-keeping
  • Intentional deviation from protocol, GCP or regulations by study personnel
  • Subject repeated non-compliance with study requirements
Please find out why the protocol requires IP administration in a specific way. Is there any impact on efficacy / safety if the order of administration is reversed? Is there a pharmaceutical / pharmacological / pk interaction between 2 drugs? If so, it will be a protocol violation.  


Source: Pharmabiz

Comments

Popular posts from this blog

FDA Restricts Use of Diabetes Drug Avandia

FDA Decides Not to Ban Avandia, but Puts Restrictions on How It’s Used.
By Daniel J. DeNoon
WebMD Health News

Sept. 23, 2010 -- The FDA will not ban Avandia -- but stringent restrictions will make it far harder for doctors to prescribe the safety-troubled diabetes drug.

The European Medicines Agency took harsher action. European sales of Avandia-containing drugs will be suspended over the next few months, although the agency did not formally withdraw approval.

The 600,000 U.S. patients currently taking Avandia can continue to take the drug only if their doctors officially attest that their patients understand the risks, that the drug is helping them, and that no other diabetes drug can keep their blood sugar under control.

New Avandia prescriptions can only be written for patients who, for medical reasons, cannot take Actos. Actos, a diabetes medication in the same class as Avandia, does not cause the heart problems linked to Avandia.

"Avandia will be available to new pat…

The Influence of TheTourniquet on blood draw

[1] Various methods are used to obtain specimens for hematocritdetermination in neonates. We evaluated arterial sampling andfound this method to be acceptable. Arterial values correlatedclosely with simultaneously obtained venous samples. Venousblood obtained with a tourniquet had a significantly higherhematocrit than that obtained without a tourniquet.[2] Influence of tourniquet application on venous blood sampling for serum chemistry, hematological parameters, leukocyte activation and erythrocyte mechanical propertiesBackground: Venous blood sampling is usually performed using a tourniquet to help locate and define peripheral veins to achieve successful and safe venipuncture. Despite widespread usage of tourniquets for venipuncture by medical and laboratory staff, very few are aware of the effects of tourniquet application on laboratory parameters. In addition, definitive guidelines regarding when and how to use a tourniquet for blood sampling are lacking. The aim of the present stu…

Isotretinoin in India: A tragedy in the offing

Isotretinoin in India: A tragedy in the offing
Wednesday, March 28, 2007 08:00 IST 
Seema Thakral

Isotretinoin is the drug of choice for severe calcitrant cystic acne vulgaris, which often causes scarring and depression from disfigurement. Isotretinoin has been called "the greatest medical advance of the 1980's." A majority of patients with acne are permanently cleared after a four to five months course of treatment. It has also been used off-label for a variety of oncology uses including: cervical cancer, head and neck cancer, squamous cell cancer of the skin, juvenile chronic myelogenous leukemia (CML), and neuroblastoma. However, the drug is a proved teratogen and carries a significant risk of birth defects, if it taken during pregnancy. Birth defects, which have been documented following isotretinoin exposure include abnormalities of the face, eyes, ears, skull, central nervous system, cardiovascular system, and thymus and parathyroid glands. There is an increased risk …