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         EDITORIAL COMMENTARY Year : 2022  |  Volume : 68  |  Issue : 3  |  Page : 129-130

Under-reporting of safety data – cause for concern

S Gajbhiye
Department of Pharmacology, All India Institute of Medical Sciences, Nagpur, Maharashtra, India

Date of Submission11-Apr-2022Date of Decision25-Apr-2022Date of Acceptance04-May-2022Date of Web Publication16-Aug-2022

Correspondence Address:
S Gajbhiye
Department of Pharmacology, All India Institute of Medical Sciences, Nagpur, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jpgm.jpgm_326_22

How to cite this article:
Gajbhiye S. Under-reporting of safety data – cause for concern. J Postgrad Med 2022;68:129-30

One of the important aspects of clinical trials is assessing safety, as the major reason for conducting a trial is to understand the benefit in light of the risk. There are various guidance documents related to how to report safety.[1] It is the responsibility of all stakeholders to report, assess, and analyse these safety reports. However, it is noted that the study team conducting the clinical trials is under an assumption that the adverse events are to be adequately managed and need not be reported if they are not 'significant'.[2]

The study conducted by Konwar et al.[3] published in the current issue, highlights a serious concern regarding the trend of under-reporting of safety data. The papers analysed in the study are from a reputed journal and the duration is over a five-year period. It is very startling to know that less than half of the randomized controlled trials (RCTs) have reported safety statistics with the significance levels or confidence intervals. A checkpoint at multiple places is needed to tackle this issue.

The development of clinical trial protocol is the responsibility of the sponsor and the sponsor must ensure the appropriate capture using case record form and elucidating reporting of safety related updates. Incorporating the patient-reported outcome in assessment of safety is very vital.[4] There are reports on inappropriate reporting of adverse events in literature. A study on recombinant human bone morphogenetic protein 2 used in spinal fusion, showed that as compared to the actual data (based on individual participant data or internal industry reports), 56% to 88% of effectiveness outcome and 23% of adverse events only were reported in published literature.[5] Another study found that 64% of adverse events were not reported in journal publication.[6] The sponsor has access to a clinical database and must meet the larger responsibility to report safety information to all stakeholders. Also, investigators must build a mechanism to reduce the influence of sponsors on the data reported.

Another important stakeholder is the investigator who apart from observing, evaluating, and managing the adverse event must ensure that all the adverse events are reported to ethics committees and sponsors. It has been reported in study conducted by Weston et al.,[7] that the safety assessment and reporting is not only incomplete but is also not conforming with protocols. Documentation of the subjective symptoms reported by participants must be ensured, because if they are neglected, it might affect treatment decisions later in clinical practice.[8] Thus, investigators have a higher responsibility on their shoulders to project the true picture regarding the potential harm in clinical trials. Also, as highlighted by the authors it is important that the reviewers or editors of the papers acquire participant data and suggest incorporation of key findings related to safety.

One of the positive findings of the study by Konwar et al.[3] is that the investigator-initiated studies (IIS) have higher reporting of safety data. These studies do have a more unbiased stand in reporting both components (benefits and risk) as suggested by this study. Landewé et al.[9] reported receiving huge data in the form of safety updates and highlighted that these can be overwhelming for the ethics committees. The safety data thus needs to be analysed appropriately and summarised in a meaningful manner when given to various stakeholders.

The downside of not reporting these safety updates could be manifold. The under-reporting of the safety updates in published literature will affect the analysis in future systematic reviews and meta-analyses. Also, it will have an impact on everyday clinical practice as the prescribers will not expect these adverse reactions and have false opinions regarding the drug's safety. The patient will be at a greater loss as the informed decision that they make while choosing a particular therapy over others with the prescribers is not based on true facts about the drug. These can also over-estimate the maximum tolerated dose which the patients may not be able to tolerate in routine practice and this might have an overall impact on compliance of therapy. The pharmacoeconomic analysis done will have to include the cost of managing the adverse reactions which might hamper the predictions made for the drug. Thus, the problem must be addressed as the observation, collection, interpretation, analysis, reporting, and dissemination of this information is extremely important to protect the safety and well-being of the society at large.

 

 :: References 
1.Food and Drug Administration. Guidance for Industry and Investigators: Safety Reporting Requirements for INDs and BA/BE Studies. Food Drug Adm 2012;32. Available from: https://www.fda.gov/files/drugs/published/Safety-Reporting-Requirements-for-INDs-%28Investigational-New-Drug-Applications%29-and-BA-BE-%28Bioavailability-Bioequivalence%29-Studies.pdf. [Last accessed on Apr 2022 Apr 07].  
    2.Sil A, Das N. Ethics of safety reporting of a clinical trial. Indian J Dermatol 2017;62:387-91.  
[PUBMED]  [Full text]  3.Konwar M, Mamde A, Patankar P, Thatte UM, Gogtay NJ. An audit of safety reporting in randomized controlled trials over a five-year period in a high impact factor journal. J Postgrad Med 2022;68:133-7.  
[PUBMED]  [Full text]  4.Heneghan C, Goldacre B, Mahtani KR. Why clinical trial outcomes fail to translate into benefits for patients. Trials 2017;18:122.  
    5.Rodgers MA, Brown JVE, Heirs MK, Higgins JPT, Mannion RJ, Simmonds MC, et al. Reporting of industry funded study outcome data: Comparison of confidential and published data on the safety and effectiveness of rhBMP-2 for spinal fusion. BMJ 2013;346:f3981.  
    6.Golder S, Loke YK, Wright K, Norman G. Reporting of adverse events in published and unpublished studies of health care interventions: A systematic review. PLoS Med 2016;13:e1002127.  
    7.Weston J, Dwan K, Altman D, Clarke M, Gamble C, Schroter S, et al. Feasibility study to examine discrepancy rates in prespeci fi ed and reported outcomes in articles submitted to The BMJ. BMJ Open 2016;6:e010075.  
    8.Liu L, Suo T, Shen Y, Geng C, Song Z, Liu F, et al. Clinicians versus patients subjective adverse events assessment : Based on patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). Qual Life Res 2020;29:3009-15.  
    9.Landewé RBM, Smolen JS, Weinblatt ME, Emery P, Dougados M, Fleischmann R, et al. Can we improve the performance and reporting of investigator-initiated clinical trials? Rheumatoid arthritis as an example. Ann Rheum Dis 2014;73:1755-60.