Karmela Krleža-Jerić

SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

Reporting of methodologic information on trial registries for quality assessment: a study of trial records retrieved from the WHO search portal

Background Although randomized clinical trials (RCTs) are considered the gold standard of evidence, their reporting is often suboptimal. Trial registries have the potential to contribute important methodologic information for critical appraisal of study results. Methods and Findings The objective of the study was to evaluate the reporting of key methodologic study characteristics in trial registries. We identified a random sample (n = 265) of actively recruiting RCTs using the World Health Organization International Clinical Trials Registry Platform (ICTRP) search portal in 2008. We assessed the reporting of relevant domains from the Cochrane Collaborations ‘Risk of bias’ tool and other key methodological aspects. Our primary outcomes were the proportion of registry records with adequate reporting of random sequence generation, allocation concealment, blinding, and trial outcomes. Two reviewers independently assessed each record. Weighted overall proportions in the ICTRP search portal for adequate reporting of sequence generation, allocation concealment, blinding (including and excluding open label RCT) and primary outcomes were 5.7% (95% CI 3.0–8.4%), 1.4% (0–2.8%), 41% (35–47%), 8.4% (4.1–13%), and 66% (60–72%), respectively. The proportion of adequately reported RCTs was higher for registries that used specific methodological fields for describing methods of randomization and allocation concealment compared to registries that did not. Concerning other key methodological aspects, weighted overall proportions of RCTs with adequately reported items were as follows: eligibility criteria (81%), secondary outcomes (46%), harm (5%) follow-up duration (62%), description of the interventions (53%) and sample size calculation (1%). Conclusions Trial registries currently contain limited methodologic information about registered RCTs. In order to permit adequate critical appraisal of trial results reported in journals and registries, trial registries should consider requesting details on key RCT methods to complement journal publications. Full protocols remain the most comprehensive source of methodologic information and should be made publicly available.

Do trialists endorse clinical trial registration? Survey of a Pubmed sample

IntroductionDespite intense interest in trial registration, there is a wide gap between theoretical postulates on trial registration and its implementation worldwide.ObjectiveWe aimed to evaluate trialists views about current international guidelines on trial registration, including the World Health Organizations (WHO) International Clinical Trials Registry Platform (ICTRP) policies and the Ottawa Statement, as well as their intention to register any future clinical trials they conduct.MethodsWe identified all 40,158 PUBMED-indexed clinical trials published from May 2005 to May 2006 using an advanced search strategy. From a random sample of 500 confirmed clinical trials, corresponding authors with e-mail contact addresses were surveyed.ResultsA total of 275 (60%) questionnaires from 45 countries were completed. 31% of the respondents had received only nonindustry funding during the past ten years, while 5% and 61% had received only industry or mixed funding respectively. Approximately two third of participants supported registration of all 20 WHO Data Set items, and endorsed the Ottawa Statement part 1 and part 2. Delayed public disclosure of some essential data in instances where they may be considered sensitive for competitive commercial reasons was supported by 30% of the participants, whereas immediate disclosure was supported by 53%. Only 21% of participants had registered all of their ongoing trials since 2005, while 47% stated that they would provide the 20 WHO Data Set items to a publicly accessible register for all their future clinical trials; a significantly higher proportion of participants who received only nonindustry funding (62%) was found among those who would always provide the 20 WHO items for future trials, compared to 42% of participants who received mixed or only industry funding. Among those who were undecided about endorsing registration. One third of participants expressed a lack of sufficient knowledge as the primary reason.ConclusionAlthough disagreement was apparent on certain issues, our findings illustrate that trial registration is gradually becoming part of the current research paradigm internationally. Our results also suggest that researchers require more knowledge to inform their decision to comply with the International standards at this early stage of voluntary trial registration.

Prospective registration and results disclosure of clinical trials in the Americas: a roadmap toward transparency

The objective of this article is to propose a roadmap toward transparency of clinical trials in the Americas by their prospective registration and results disclosure. This will broaden access to more complete and accurate data and facilitate evidence-informed decision-making and participation in research. Consequently, it should have a positive impact on peoples health and should promote trust in health research. Existing initiatives were identified, registration of trials was analyzed following the World Health Organization (WHO) standards on trial registration, and a roadmap is proposed to address the gaps in advancing transparency. The analysis shows that, in spite of numerous regional and country initiatives, clinical trials taking place in nonEnglish-speaking parts of the Americas are underregistered. A roadmap is proposed to enhance research governance and good research practice by improving the transparency of clinical trials. The proposed roadmap includes strategies for implementing WHO international standards for trial registration, for developing international standards of public disclosure of trial results, and for a potential role of the Pan American Health Organization.

Sharing and reuse of individual participant data from clinical trials: principles and recommendations

Objectives We examined major issues associated with sharing of individual clinical trial data and developed a consensus document on providing access to individual participant data from clinical trials, using a broad interdisciplinary approach. Design and methods This was a consensus-building process among the members of a multistakeholder task force, involving a wide range of experts (researchers, patient representatives, methodologists, information technology experts, and representatives from funders, infrastructures and standards development organisations). An independent facilitator supported the process using the nominal group technique. The consensus was reached in a series of three workshops held over 1 year, supported by exchange of documents and teleconferences within focused subgroups when needed. This work was set within the Horizon 2020-funded project CORBEL (Coordinated Research Infrastructures Building Enduring Life-science Services) and coordinated by the European Clinical Research Infrastructure Network. Thus, the focus was on non-commercial trials and the perspective mainly European. Outcome We developed principles and practical recommendations on how to share data from clinical trials. Results The task force reached consensus on 10 principles and 50 recommendations, representing the fundamental requirements of any framework used for the sharing of clinical trials data. The document covers the following main areas: making data sharing a reality (eg, cultural change, academic incentives, funding), consent for data sharing, protection of trial participants (eg, de-identification), data standards, rights, types and management of access (eg, data request and access models), data management and repositories, discoverability, and metadata. Conclusions The adoption of the recommendations in this document would help to promote and support data sharing and reuse among researchers, adequately inform trial participants and protect their rights, and provide effective and efficient systems for preparing, storing and accessing data. The recommendations now need to be implemented and tested in practice. Further work needs to be done to integrate these proposals with those from other geographical areas and other academic domains.

Spirit 2013 statement: Defining standard protocol items for clinical trials

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

Clinical Trials Registries and Results Databases

Trial registration and results disclosure are considered powerful tools for achieving higher levels of transparency and accountability for clinical trials. New emphasis on knowledge sharing and growing demands for transparency in clinical research are contributing to a major paradigm shift in health research that is well underway. In this new paradigm, knowledge will be generated from the culmination of all existing knowledge – not just from parts and bits of previous knowledge, as is largely the case now. The full transparency of clinical research is a powerful strategy to diminish publication bias, increase accountability, avoid unnecessary duplication of research, advance research more efficiently, provide more reliable evidence for diagnostic and therapeutic prescriptions, and regain public trust. Transparency of clinical trials, at a minimum, means sharing information about design, conduct, and results. The information itself must be explicitly documented, but then an access location or medium for distribution must be provided. In the case of clinical trials, the public disclosure of data is realized by posting them in well-defined, freely accessible clinical trial registries and results databases.

Outcome reporting bias in government-funded RCTs

In response to Pasquale Moja and associates, we would first like to clarify 2 points in their letter. First, it would be more accurate to state that a median of 26 outcomes was declared in both the protocols and the publications, rather than in the protocols alone. Also, with regard to the assertion