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Title: An Overview to Voluntary Harmonization Procedure (VHP)-Approach to Clinical Trial Applications (CTA)

Authors: Anil Eknath Khedkar

Topic: Clinical Research

Abstract:

The clinical trial application (CTA) approval in the European Union (EU) member state has been subject to national legislation. Due to this the assessment of a CTA that was filed simultaneously in several EU member states often resulted in varying final decisions and unnecessary delays. Sometimes country-specific modifications to the application often occurred due to changes requested by the different regulatory/competent authorities (RA/CA) and ethics committees (EC). Sometimes a clinical trial might even be approved in one member state and rejected in another. The whole procedure could be extremely time-consuming and the country-specific modifications risk the scientific value of clinical trial results. The Voluntary Harmonisation Procedure (VHP) offers sponsors of multinational clinical trials involving three or more EU member states a harmonised procedure for the regulatory assessment of clinical trial authorisation applications. The Voluntary Harmonisation Procedure makes it possible to obtain a coordinated assessment of an application for a clinical trial that is to take place in several European countries.

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    COMMENT - 1

  • PRAJNA KUMAR (Viewer) 29th Jan 2015 - 7:48 PM
    A good read and general overview of the VHP process, however the information in the article is already available via myriads of available literature. Could not find anything novel or exciting to address the inefficiencies in the current process. At present the way the article is designed it lacks direction or meaningful recommendations. The article also fails to cite references in the body. The article also has several abbreviations and does not spell it out for the readers.

    It would have been meaningful to see how the directive has improved the conduct of clinical trials and how the harmonization of core requirements, has provided greater assurance of patient safety and clinical data quality to support the Marketing Authorization Application. It would have been beneficial to see a comparative analysis of pros and cons using the VHP, current challenges and future recommendation to simplify the process or make it more streamlined and efficient.

    The VHP offers a short- to medium-term alternative to the purely national system of the management of clinical trials in the EU. However, it applies only to health authority submissions, not to Ethics Committees or Institutional Review Board submissions. An overview of how this is impacting current submissions and recommendations to improve could have been meaningful from publication perspective.

    Also, the VHP is not anchored in any EU directive or regulation, and countries can opt out of the procedure if they wish. This results in uncertainties for overall clinical development. Recommendations for how this could be managed would have been meaningful for publication or policy recommendations.

    A retrospective analysis of studies that have used VHP process and the savings in resource and how it aligns with CT cost could have been another interesting perspective o research on.

    Some of the recommendations could have been

    1. All submissions in electronic in one electronic formats
    2. A common application form for all NCA and ECs in English and no ‘extra’ national forms
    3. One harmonized checklist for national submission documents including Ethics Committees and no local ‘additional documents’
    4. English as only language for all clinical trial regulatory documents, will help reduce translation requirements to documents for the public and trial participants 5.Integration of EC assessment and feedback into the VHP process and timelines – perhaps with an ‘EC coordinator 6. More EU guidance and training for EC members on
    – Advances in protocol design (e.g. adaptive design)
    – Standardizing informed consent requirements
    – EU harmonized data protection requirements

    The article mentions an interesting fact that the CTA applications in EU has decreased from 2007 to 2010, how this ties in with VHP process was not mentioned and if it does, then this would have been an interesting study to investigate.
    Another angle from VHP process and interesting topic to discover would have been challenges sponsors/CROs are facing with the VHP process and a prospective survey analysis to investigate this would have been interesting.

    All in all, interesting topic, several possibilities to strengthen the article and there are several opportunities to explore this topic from benefit to CT cost and resource and future possibilities of this process streamlining and utilized by global regulatory bodies and recommendations in that direction would have been critical from publication perspective.
    • ANIL EKNATH KHEDKAR (Author) 9th Feb 2015 - 4:45 PM
      Dear Prajna Kumar,

      Thanks for your time to review the article. I appreciate your comments over the harmonization process and the the key recommendations.

      For the CTA future there are three main issues:
      (1) the divergent application of the Clinical Trials Directive in the Member States;
      (2) the increased administrative burden for clinical trials in view of regulatory requirements which do not take into account practical necessities and
      constraints;
      (3) the fact that clinical trial regulation does not sufficiently take into account the increasingly global scale of clinical trials.

      There is discussing on going within health authorities and stake holder for improvement to the current legislation and process;

      Single application for Ethics and Regulatory
      approval
      • Consistent submission requirements and format
      • Greater predictability over review times for multi country studies
      • Shorter review times for multi country studies
      • Acknowledgement of the risk level of the trial
      • Inclusion of the concept of co-sponsorship of trials
      • National indemnification schemes for noncommercial sponsors

      Hopefully we will see more advancement to the current legislation for harmonization in the application process.

  • COMMENT - 2

  • MADHURI DINESHBHAI PATEL (Viewer) 1st Feb 2015 - 4:30 PM
    Dear Anil, the article is well structured and provides important information regarding VHP and importance of standardization. As a researcher, we are facing certain problems which could be handled well if systems are harmonized. Pharmaceutical and clinical research industries embraced globalization as a core component of business. In this scenario we also should focus on how the VHP model can be implemented and used to improve quality standard in other countries as well.
    • ANIL EKNATH KHEDKAR (Author) 9th Feb 2015 - 4:50 PM
      Dear Madhuri Patel ,

      Thanks for your comments and I am glad you found this article useful for research purpose and its implementation across the globe .

      At the moment the health authorities and stake holders having discussion on improvement to the current legislation and the application process within EU and by 2016 we may see the new harmonised process and subsequently this can be used by other countries to improve quality standards in clinical trials authorization.

  • COMMENT - 3

  • PRANEETH KUMAR (Viewer) 3rd Feb 2015 - 2:27 PM
    Mr. anil . the topic was very interesting. A decent read and general outline of the VHP process, however the data in the article is now accessible by means of heaps of accessible writing. Couldn't discover anything novel or energizing to address the inefficiencies in the current procedure. At present the way the article is composed it needs bearing or important proposals. The article additionally neglects to refer to references in the body. The article likewise has a few shortenings and does not delineate it for the perusers.
    • ANIL EKNATH KHEDKAR (Author) 9th Feb 2015 - 4:57 PM
      Dear Praneeth kamarapu,

      Thanks for your time to review the article. I appreciate your comments and recommendations.

      Currently there is a discussion on going within health authorities and stake holder for improvement to the current legislation and process like single application for Ethics and Regulatory approval, Consistent submission requirements and format, Greater predictability over review times for multi country studies, Shorter review times for multi country studies, Acknowledgement of the risk level of the trial, Inclusion of the concept of co-sponsorship of trials, National indemnification schemes for non-commercial sponsors.

      By 2016 we may see more advancement and harmonization to the current application process and updated legislative system..

  • COMMENT - 4

  • MANAN K TRIVEDI (Viewer) 5th Feb 2015 - 5:08 PM
    Good initiative in EU but i think there is already centralized procedure and de-centralized procedure already present such approval but thing is that if you opt for centralized you are covered for all EU MS not specific to 2 or 3 MS so if sponsor plans to get CTA approval in customized way perhaps this procedure will be helpful for 3-4 countries or MS?
    Also similar kind of Asian countries initiative and other initiative should Standard to avoid delay in approval procedures.
    • ANIL EKNATH KHEDKAR (Author) 9th Feb 2015 - 5:02 PM
      Dear Manan,

      Thanks for your time to read through the article.

      At the moment there are centralized and decentralized processes in place for marketing authorization application (MAA). For clinical trails application (CTA) there are teo routes of applications national and voluntary hospitalization procedure (VHP) - which is discussed in this article.

      Currently the health authorities and stake holders having discussion on improvement to the current legislation and the application process within EU and by 2016 we may see the new harmonised process and subsequently this can be used by other countries to improve quality standards in clinical trials authorization.

  • COMMENT - 5

  • AVI NAHAR (Viewer) 7th Feb 2015 - 8:44 PM
    Dear Anil Eknath Khedkar,

    As was stated by me in the earlier phase of discussion, congratulations once again, for a well structured & very informative review of article. VHP is something still very new for developing Asian nations & it will be great to have such standards & processes laid down which are internationally acceptable. Hopefully, this will lead to more effective Trials on large scale & across the regions with meaningful conclusions.
    • ANIL EKNATH KHEDKAR (Author) 9th Feb 2015 - 5:07 PM
      Dear Dr. Avi Nahar,

      Thanks for your time to read through the article and your comments.

      Certainly VHP is good intiative taken by EU to improve authorisation process. Currently there is a discussion on going within health authorities and stake holder for improvement to the current legislation and process.

      Entry into force 2014; Application from 2016
      • Being debated by European Parliament – 754 Members from, 27 Member States
      • Three year period where both systems are in place

      After successful implementation of new legislation in EU, hopefully other countries may use that as a base to make harmonized way of application in respective regions and across the globe.
      • AVI NAHAR (Viewer) 9th Feb 2015 - 5:25 PM
        Dear Mr. Anil Khedkar,
        Looking forward to it Sir! Harmonization of processes will help maintaining uniformity as well as quality of Study designs.

  • COMMENT - 6

  • ANIL EKNATH KHEDKAR (Author) 9th Feb 2015 - 4:57 PM
    Dear Praneeth kamarapu,

    Thanks for your time to review the article. I appreciate your comments and recommendations.

    Currently there is a discussion on going within health authorities and stake holder for improvement to the current legislation and process like single application for Ethics and Regulatory approval, Consistent submission requirements and format, Greater predictability over review times for multi country studies, Shorter review times for multi country studies, Acknowledgement of the risk level of the trial, Inclusion of the concept of co-sponsorship of trials, National indemnification schemes for non-commercial sponsors.

    By 2016 we may see more advancement and harmonization to the current application process and updated legislative system..