Contact Us

Home

About us

Services

AI Excellence

case studies

publications

HEOR Certificationheor Certification

AI for Medical Writing

Contact

  • An Overview Of The EMA Proactive Transparency Policy (EMA Policy 0070)

    An Overview Of The EMA Proactive Transparency Policy (EMA Policy 0070)

    The policy on “publication of clinical data for medicinal products for human use”, also referred to as the “policy 0070” was launched in 2015 by the European Medicines Agency (EMA), to comply with the growing demand from stakeholders for additional transparency in the clinical data that form the basis of regulatory decisions. (1-3)

    Policy 0070 allows global access to regulatory documents for non-commercial reasons. The policy defines ‘clinical data’ to include clinical overviews, summaries, and clinical study reports (CSRs), along with the CSR appendices [including protocol and protocol amendments, sample case report form(s) and documentation of statistical methods (clinical study statistical analysis plan (SAP)]. Under this policy, clinical data is published through central regulatory applications in an anonymised portable document format. The reason for anonymity is to ensure that the public disclosure of data will lower the risk of re-identification of trial participants from the information available contained within these documents, including any retained narrative information relating to individual participants.(4, 5) In simple words, this policy enables people, including researchers and academics, to precisely access information from the CSRs submitted by pharmaceutical companies to EMA pertaining to the marketing authorisation applications for new medicines.(6)

    The original Policy 0070 document had two phases, phase 1 was about the publication of only CSRs; while phase 2 was slated for a later implementation and will look into the publication of individual patient data (IPD).(1, 3) However, the revision of the policy in 2019 covered both CSRs and IPD under ‘clinical data’.(2)

    EMA believes that such refined transparency initiative will bring regulators one step closer to the EU citizens and promote well-informed use of medicines. Additionally, it is also estimated that the access to clinical data will benefit future public health. By creating a platform for all medicine developers to learn from the past successes and failures, the policy has demonstrated the ability for a more efficient medicine development. Furthermore, it will help the global scientific community to make use of a wide range of clinical data to establish new evidence in the interest of public health. Access to clinical data will facilitate third party verification of the original research to further analyse and assess the regulators’ positions and challenge them where deemed fit.(3)

    Going by the same principles, the EMA launched exceptional measures during the COVID-19 pandemic to enhance the transparency of its regulatory activities on COVID-19 treatments and vaccines that are either approved or are under evaluation for approval. The purpose of these measures is to regulate the high interest for information while supporting the worldwide research on COVID-19 treatments.(7, 8)

    Globally, EMA is the first regulatory body to offer open access to clinical data submitted by companies for marketing authorisation applications. Moreover, this proactive transparency policy has moved the worldwide conversation towards more transparency, as other regulators, like the US Food and Drug Administration (USFDA) and Health Canada, have eventually implemented – or are planning to implement – similar transparency initiatives.(6)

    Become A Certified HEOR Professional – Enrol yourself here!

    References

    1. European Medicines Agency policy on publication of clinical data for medicinal products for human use. (EMA/240810/2013)
    2. European Medicines Agency policy on publication of clinical data for medicinal products for human use. 2019 Revision. (EMA/144064/2019). Available at: https://www.ema.europa.eu/en/documents/other/european-medicines-agency-policy-publication-clinical-data-medicinal-products-human-use_en.pdf
    3. External guidance on the implementation of the European Medicines Agency policy on the publication of clinical data for medicinal products for human use. (EMA/90915/2016). Available at: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/external-guidance-implementation-european-medicines-agency-policy-publication-clinical-data_en-1.pdf
    4. Ferran JM, Nevitt SJ. European Medicines Agency Policy 0070: an exploratory review of data utility in clinical study reports for academic research. BMC Med Res Methodol 2019; 19(204).
    5. European Medicines Agency: External guidance on the implementation of the European Medicines Agency policy on the publication of clinical data for medicinal products for human use, Revision 3. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_001799.jsp&mid=WC0b01ac0580b2f6ba
    6. European Medicines Agency: News: EMA’s proactive publication of clinical data a success. July 2018. Available at: https://www.ema.europa.eu/en/news/emas-proactive-publication-clinical-data-success
    7. European Medicines Agency: News: Extra transparency measures for COVID-19 vaccines and therapeutics. October 2019. Available at: https://www.ema.europa.eu/en/news/extra-transparency-measures-covid-19-vaccines-therapeutics
    8. European Medicines Agency. Transparency: exceptional measures for COVID-19 medicines, Available at: https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/transparency-exceptional-measures-covid-19-medicines

    MarksMan Healthcare

    ,

  • Publication Bias, Favourable Results And Publicly Funded Studies

    Publication Bias, Favourable Results And Publicly Funded Studies

    Clinical practice should ideally rely on robust scientific evidence, the standard for which are systematic reviews and meta-analyses of all randomised controlled trials (RCTs). (1,2) Therapeutic decisions in healthcare must be informed by clinical research findings, and patients and prescribers must be able to trust the presented research evidence. However, this evidence can be considered valid only if the studies included in reviews and meta-analyses signify the complete publications, without any bias. (2) Recently, the reliability of much of the evidence base for several popular therapeutic and preventive interventions has been challenged due to the publication bias. (3)

    What is ‘publication bias’? It refers to data distortion in scientific journals mainly due to the increased likeliness of publications of those studies with significant and positive results compared to those with unfavourable or negative or insignificant results. (2)  Publication bias, in essence, is a threat to the core principle of evidence-based medicine that is based on systematic reviews of published evidence providing accurate assessments of an intervention’s actual safety and efficacy data. (4) Moreover, the methods used to conduct the systematic review represent their validity. The presence of a systematic bias of favouring the publication of studies with statistically significant or positive findings substantially threatens the validity of the conclusions of a systematic review. (5) Study selection based on their status of publication (submitted or accepted), duplicate, undetected publications, and selective reporting are some of the factors that lead to publication bias. In addition, the bias also occurs when the publication selectively depends on the nature and direction of the study findings, (6) which will then be thoroughly different from those of unpublished studies.(2)

    Evidence from literature confirms that the probability of the publication of studies with positive and favourable results is more than that of studies with negative or unfavourable results.(1,2,7) For instance, a systematic review and meta-analysis of 85 cohorts assessed their likelihood of publication based on different variables, such as favourability of results, statistical significance, study sponsorship, number of study centers, study phases, study design, study size, and country of origin; with the outcome of interest being complete publication in a peer-reviewed journal.(4) The authors found that favourability of results, statistical significance, and multicenter status were all significantly impacted the probability of publication. Moreover, the likeliness of publication of the studies presented as abstracts was significantly higher if a sponsor funded the studies. Therefore, the likeliness of publication for favourable study findings was significantly influenced by the study’s funding status.(3) This only goes on to suggest a strong association of differential publication due to the favourability of study findings and the status of sponsorship from the industry.(4)

    The decision-making in clinical and medical practice should depend on the entirety of research evidence and not on a sample that is biased by selective publication only of studies showing favourable findings.(6) To overcome the hurdle of bias and support the complete, unbiased publication of studies, researchers are suggesting a mandate for clinical trials to register before recruiting patients so that the authors of systematic reviews know about all potentially eligible studies, notwithstanding their findings. It will also help if authors of systematic reviews ensured the assessment of the potential problems of publication bias in their review, thus considering methods for addressing this issue and confirming an inclusive search for both published and unpublished trials. (5) Finally, precise and robust measures, if taken by the scientific and medical organizations, ethical committees, regulatory bodies, journal editors, and the industry itself, will ensure that commercial interests of pharmaceutical companies do not weaken the knowledge of scientifically correct study planning, study execution, and publication.(2)

    Become A Certified HEOR Professional – Enrol yourself here!

    References  

    1. Melander H, Ahlqvist-Rastad J, Meijer G, Beermann B. Evidence b(i)ased medicine: selective reporting from studies sponsored by pharmaceutical industry; review of studies in new drug applications. BMJ. 2003; 326:1171-3.
    2. Kerekovska A, Galunska B. Publication bias in clinical research sponsored by pharmaceutical industry. Scripta Scientifica Pharmaceutica. 2014; 1:7-13.
    3. Jefferson T. Sponsorship bias in clinical trials: growing menace or dawning realisation? Journal of the Royal Society of Medicine. 2020; 113(4):148-157.
    4. Canestaro WJ, Hendrix N, Bansal A, et al. Favorable and publicly funded studies are more likely to be published: a systematic review and meta-analysis. J Clin Epidemiol. 2017; 92:58-68.
    5. Hopewell S, Loudon K, Clarke MJ, et al. Publication bias in clinical trials due to statistical significance or direction of trial results. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: MR000006.
    6. Song F, Eastwood AJ, Gilbody S, et al. Publication and related biases. Health Technology Assessment. 2000; 4(10):1-105.
    7. McGauran N, Wieseler B, Kreis J, et al. Reporting bias in medical research – a narrative review. BioMed Central Trials. 2010; 11:37.

    MarksMan Healthcare

    ,

  • The Impact Of PRISMA Statement On Systematic Review Publications

    The Impact Of PRISMA Statement On Systematic Review Publications

    Systematic reviews (SRs) are crucial in health and scientific research as they offer a thorough understanding of the findings from research. (1) They provide critical information on different aspects of research, such as answers to the questions not often addressed by individual studies, problems in primary research that need to be avoided in future studies, and theories on how’s and why’s. Therefore, they create a knowledge base for different types of stakeholders, viz. healthcare providers, patients, fellow researchers, as well as regulators and policymakers. (2)

    An SR is valuable only when it is prepared with transparent, comprehensive, and precise objectives. If the information presented in SRs is ambiguous, the readers may not interpret or reproduce the findings precisely. Additionally, it may also lead to the failure to implement the SR findings into clinical practice. (3) Adherence to clear, up-to-date reporting guidelines enables authors to achieve reliable, good-quality SRs. (4,5)

    The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement is a reporting guideline published in 2009, developed to curb poor reporting of SRs. (6) This statement comprises a checklist of 27 items recommended for reporting in SRs, as well as an “explanation and elaboration” paper that provides additional regulations for an individual item, along with examples of exemplar reporting. (7) As observed in 2017, the PRISMA 2009 statement reportedly had a very high uptake from the biomedical research community. However, not all published SRs were observed to cite the guideline. (8) As of 2020, the endorsement and adoption of the statement were more expansive, as observed through its co-publication in several journals, citation in over 60,000 reports, (9) commendation from nearly 200 journals, SR organizations, and uptake in various fields.(2)

    The PRISMA 2009 statement and extensions certainly helped in facilitating meta-research. Evidence also suggests that adherence to some PRISMA items was better than others. (3) Moreover, findings from observational studies have shown the use of the PRISMA 2009 statement to result in thorough reporting of SRs,(8) although with more scope to improve adherence to the same. (3) A scoping review was conducted to analyze the uptake and impact of the PRISMA 2009 statement, which considered 57 studies assessing adherence to the statement (reporting of SRs in line with PRISMA 2009 guidance).(3) Findings of this review showed, out of 57 studies considered, adherence to the statement was reported in 27 studies. However, lack of transparency was still an issue for many published SRs, which was shown with adherence shown to very few items from the statement among very few SRs.(3)

    In 2020, the PRISMA 2009 statement was updated and replaced by PRISMA 2020 statement. This update can be attributed to the perpetual changes in the health and life sciences research domain, such as technological advancements like natural language processing (NLP) and machine learning (ML) for robust identification of relevant evidence, development of novel methods for assessing the risk of bias, and transformation of publishing landscape, among others.2 The PRISMA 2020 statement provides updated reporting recommendations for SRs that consider advancements in methods to identify, select, and assess studies. This updated statement comprises a checklist of 27 items, an extended checklist detailing guidance for an individual item, the PRISMA 2020 abstract checklist, and amended flow diagrams for original and updated reviews.(2)

    It is believed that the use of PRISMA 2020 will potentially benefit many stakeholders, including authors, editors, peer reviewers for SRs, along with a varied range of SR audiences, including guideline developers, policymakers, healthcare providers, and patients among others. Furthermore, the uptake of the PRISMA 2020 guidance will lead to a more transparent, comprehensive, and precise SR reporting, thus enabling informed and evidence-based decision-making.(2)

    Become A Certified HEOR Professional – Enrol yourself here!

    References  

    1. Peričić T, Tanveer S. Why systematic reviews matter – A brief history, overview and practical guide for authors. Author’s Update. Elsevier. July 2019. Available at: https://www.elsevier.com/connect/authors-update/why-systematic-reviews-matter
    2. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372:n71.
    3. Page MJ, Moher D. Evaluations of the uptake and impact of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement and extensions: a scoping review. Syst Rev 2017; 6:263.
    4. Moher D, Tetzlaff J, Tricco AC, Sampson M, Altman DG. Epidemiology and reporting characteristics of systematic reviews. PLoS Med 2007; 4:e78.
    5. Page MJ, Moher D. Mass production of systematic reviews and metaanalyses: an exercise in mega-silliness? Milbank Q 2016; 94(3):515-9.
    6. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009; 151:264-9, W64.
    7. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009; 62:e1-34.
    8. Page MJ, Shamseer L, Altman DG, et al. Epidemiology and reporting characteristics of systematic reviews of biomedical research: a cross-sectional study. PLoS Med 2016; 13(5):e1002028.
    9. Scopus Preview. August 2020. Available at: https://www.scopus.com/home.uri?zone=header&origin=

    MarksMan Healthcare

    , , ,