NIS Considerations
CHCUK NewsletterOctober/November 2010
In this Month's Issue
Latvia: New NIS Regulations
Romania: Updated COP
GRACE Principles
UK: Proportionate Ethics Review
Advertising Opportunity: NIS Report - Europe Part 2
CHCUK NIS Regulatory Map




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Welcome to the October/November edition of our NIS Considerations newsletter.

If you have previously prchased a copy of Part 1 of our NIS report and haven't yet received a copy of the 2nd Edition please contact me as soon as possible.

Best wishes,

Stuart McCully
Tel: +44 (0) 1997 42 33 11
Mobile: +44 (0) 7909 111 510
Latvia: New NIS Regulations
Cabinet Regulation 289 Lays Down Requirements for Obs Studies 
Latvian Flag
Cabinet Regulations No 172 of 28th February 2006 has been replaced/ repealed by Cabinet Regulations No 289 of 23rd March 2010 which now lays down requirements for Observational Studies in Latvia which include the requirement for both Competent Authority and Ethics Committee approval prior to study start.

Prior to commencement of observational studies, a physician or a representative of the medicinal product manufacturer, who is responsible for coordination of the observational study, shall submit the below listed documents to the State Agency of Medicines and the Ethics Committee:

An application containing the following details:

  • Name of the observed medicinal product, its generalized name, form and strength;

  • Description of the observational study project (as well as criteria for inclusion of patients in the observational study and data analysis methods to be used);

  • Physicians participating in the conduct of the observational study, stating the name, surname and speciality);

  • Medical institutions participating in the conduct of the observational study;

  • The planned number of patients to be involved;

  • Whether the disease, which is supposed to be treated using the observed medicinal product, is included into the medicine refund system;

  • Whether the observed medicinal product is included into the list of refunded medicines;

  • Period of the observational study, stating the days of commencement and completion;

  • A specimen of a document whereby a patient shall certify his/her consent to the treatment data collection and processing;

  • A specimen of an observational data recoding document

The applicant shall cover all costs related to reviewing of his/her request for authorization of an observational study in accordance with the State Agency of Medicines' pricelist for public services.


An observational study may be commenced if the Ethics Committee has issued a favourable opinion and the State Agency of Medicines has not informed the applicant of its grounds for non-acceptance within 30 days of the day the request was filed.


The physician shall report any adverse drug-related reactions stated during the observational study to the State Agency of Medicines in compliance with the regulation on adverse reaction surveillance.


Within 90 days of completion of an observational study, the physician or the person referred to in Paragraph 129 of these Regulations, shall notify the State Agency of Medicines in writing about the completion of the observational study and submit a consolidated report on the number of patients involved and any adverse drug-related reactions stated.


The compliance of observational studies with these Regulations shall be supervised by the State Agency of Medicines and inspected by the Health Inspection within the limits of their competency.


Persons involved in observational studies shall not disclose the personal and clinical data of the patients except in cases the said data are requested by the institutions, which are entitled to familiarize themselves with patient's data as provided by the Law on Medical Care.

These regulations came into effect on 1 April 2010.

For further information refer to:

Cabinet Regulations No 289: Procedures for Clinical Trials and Observational Studies of Administration of Medicinal Products, Marking of Investigational Medicines and Assessment of Conformity to Good Clinical Practice
Romania: Updated COP
ARPIMs Code of Practice has been Updated
The ARPIM CODE OF ETHICS IN THE PROMOTION OF MEDICINES has been updated.  The 2010 version came into effect on 1 April 2010.

There are no evident changes to Article 14 (Non-interventional Studies).  However, the reader is cautioned to verify this for themselves.
GRACE Principles
IPSE Endorses the GRACE Principles
Grace Principles
As of April 2010, the International Society of Pharmacoepidemiology (IPSE) has endorsed the "GRACE Principles".

According to the document summary:

"The GRACE principles describe a hierarchy of evidence for observational research on comparative effectiveness that can be used by decision-makers, as well as key elements of good practice including defining research questions and methods a priori; collecting valid, clinically relevant data; analyzing, interpreting and reporting data, including sensitivity analyses and alternative explanations for findings; and conducting these studies in accordance with accepted good practices. This living document is formed as three groups of questions that can be used to evaluate studies; it also provides guidance about what constitutes higher quality in terms of the accuracy of information generated and how to evaluate areas of uncertainty. No scoring system is provided or encouraged, since interpretation of these studies requires weighing all available evidence, tempered by judgment of their applicability to routine care."

This is obviously very topical given the recent news (refer to link) that The Agency for Healthcare Research and Quality (AHRQ) of the US Department for Health and Human Services (HHS) has awarded US$473 million in grants and contracts to support projects concerned with patient-centred outcomes or comparative effectiveness research.
UK: Proportionate Ethics Review
UK NRES Extends its Proportionate Review Pilot to the Whole of England

The UK's National research Ethics Service recently piloted a "propotionate Review" initiative which allowed applicants to submit research they consider to present no material ethical issues for proportionate review.  The benefits being that, should the application be valid, the review takes just 14 days versus the standard 60 days.

This initiative has been extended to the whole of England.

For your application to be suitable for proportionate review, it should fit one of the categories listed in the No Material Ethical Issues Tool (NMEIT):

  • Research using data or tissue that is anonymous TO THE RESEARCHER
  • Research using existing tissue samples already taken with consent for research
  • Research using "extra tissue" (e.g. further blood taken at time of routine sampling or tissue taken at "clinically directed" operation)
  • Questionnaire research that does NOT include highly sensitive areas or where accidental disclosure would NOT have serious consequences
  • Research interview / focus group that does NOT include highly sensitive areas or where accidental disclosure would NOT have serious consequences
  • Research surveying the safety or efficacy of established non drug treatments, involving limited intervention and NO change to the patients' treatment
Full details can be found on the NRES Website
Advertising Opportunity: NIS Report - Europe Part 2
Part 2 of the NIS (Europe) Report is now being Updated
CHCUK Service Providers
Part 2 of our series of reports on NIS in Europe is now due for revision and will be provded free of charge, once revised, to any clients who have previously purchased the report.

If any clients wish to advertise their services within the report, you will be pleased to know that we are adding a new ""SERVICE PROVIDERS" section to each of the country sub-sections to aid readers in finding country-specific service providers.  Further information can be found in our "Information for Advertisers " document.

The prices listed below are inclusive of an advert placed in all 17 country-specific sections:
  • Text only entry: 75
  • Full A4 graphical advert: 250
  • Half A4 graphical Advert: 125
If you would like to take advantage of this opportunity, please note your interest by 30 Novermber 2010

Telephone: +44 1997 42 33 11

CHCUK NIS Regulatory Map
The CHCUK NIS Regulatory Map has been Updated
NIS Regulatory Map (Oct 2010)
We've recently updated the NIS Regulatory map on our website.

Reason for Update:
  • Added link to the GRACE Principles for observational comparative effectiveness research wich were endorsed by IPSE in April 2010
  • Added a link to the 2009 edition of the WHO/CIOMs International Ethical Guidelines for Epidemiolgical Studies
  • Added a link to ICH E6
  • Updated the link to the European Commission's guidance document applying to clinical trials (Eudralex Volume 10 - Chapter 5: Questions and Answers, Version 7 ) which was revised in September 2010
  • Updated Regulatory Map to include a summary of the UK requirements for NIS