Review Article

Quality of the systematic reviews in cochrane multiple sclerosis related articles

Introduction

In recent decades, the remarkable proliferation of journals and articles, considering the advancements in medical science, has brought the structure of articles and research methodology into sharper focus.^1,2 It is clear that the quality of articles directly influences the quality of results; therefore, it is vital to adhere to the research principles. Substandard research can negatively impact healthcare quality, influencing public health policies and treatments in detrimental ways.¹ Systematic reviews and meta-analyses, as the most reliable sources of information, play a pivotal role in synthesizing data from available evidence. The quality of these reviews is paramount, as they often guide clinical practice and policy.³ The methodological quality of randomized controlled trials (RCTs) included in systematic reviews can vary, considering the reliability of the review’s conclusions. The Cochrane Database of Systematic Reviews is a collection of high-quality, independent evidence, designed to inform healthcare decision-making. This database, which contains systematic reviews and meta-analyses of healthcare interventions, is widely recognized as a reliable source of current information on the effectiveness of healthcare treatments. Each review within the database, undergoes a rigorous editorial process to ensure its quality and relevance, making it an invaluable resource for healthcare professionals, researchers, and policymakers. This database comprises 53 review groups, each concentrating on a specific topic, including the Cochrane Multiple Sclerosis (MS) group.

MS, the most common non-traumatic disability in young adults, is not confined by geographical boundaries, and its prevalence is increasing in both developed and developing countries.^4,5 This disease occurs more frequently in the age range of 20 to 45 years and is twice as common in women as in men.^6-8 Factors such as genetics and environmental influences, including exposure to sunlight for vitamin D, ultraviolet radiation, the Epstein-Barr virus, obesity, and smoking, have a significant impact on patients with MS.⁹

For MS patients, where treatment decisions can profoundly affect the quality of life, the stakes are particularly high. Assessing the quality of studies and interventions becomes not just a matter of academic rigor but a necessity for ensuring patient safety and optimal outcomes. The “risk of bias”, “sample size”, and “blinding” are among the critical factors that determine the quality of a study. In this context, the article aims to explore the methodologies employed in assessing RCT quality within systematic reviews, with a focus on those of MS. It will delve into the challenges faced in this endeavor and propose strategies to overcome them, ultimately aiming to contribute to the enhancement of healthcare quality for MS patients.

Methods

This study was conducted on 57 articles published by the Cochrane Neurological Condition Group until July 2023. We searched the Cochrane database in July 2023 and included all systematic reviews and meta-analyses published up to that date. Studies involving animals and those that did not assess bias as per the Cochrane risk of bias tool were excluded. The Cochrane Library comprises databases that contain a wealth of high-quality, independent evidence. The Cochrane Neurology Group covers a range of topics including stroke, dementia and cognitive disorders, epilepsy, peripheral neuropathies, movement disorders, headache and migraine, cancers, motor neuron disease, neurodevelopmental disorders, neuromuscular junction disorders, spinal cord disorders, sleep disorders, and MS. As of the search date, it consisted of 1001 Cochrane reviews and 215 protocols. We accessed the Cochrane Library using a subscription managed by our organization and selected reviews on MS. Initially, we extracted general information from all studies, including topics, year of publication, author names, and other required information such as interventions, outcomes, and results.

We applied the Joanna Briggs Institute (JBI) Critical Appraisal tool, which contains 11 questions, to each Cochrane review to assess the risk of bias. The validity of the reviews was evaluated by two reviewers using standardized critical appraisal instruments from the JBI (JBI-MAStARI). Any disagreements were resolved through discussion, and if consensus could not be reached, a third assessor was consulted. The JBI is an international research organization specializing in evidence-based healthcare. It is renowned for promoting the synthesis, transfer, and utilization of evidence in healthcare. The Institute provides resources to help healthcare professionals integrate the best available evidence into their practice. The JBI critical appraisal tools used in this study are designed to help users assess the methodological quality of research studies, thereby determining the availability and reliability of the study results. These tools are particularly useful for researchers conducting systematic reviews or evidence synthesis. Each tool provides a checklist of specific criteria to be considered when evaluating a study, such as the appropriateness of the study design, the methods used for data collection and analysis, potential biases, and the relevance of the results. Responses to these criteria are “yes”, “no”, “unclear”, or “not applicable”. The PRISMA statement is a widely recognized set of guidelines for reporting systematic reviews and meta-analysis in health research. It helps authors improve the reporting of their results, thereby facilitating critical appraisal and interpretation.

We first assessed the included systematic reviews and meta-analyses through critical appraisal. Then, we extracted a collection of biases from all understudied RCTs in these systematic reviews, which were appraised by the authors of the systematic reviews using the Cochrane standard risk of bias tool. Finally, we extracted the results of the risk of bias assessment in each Cochrane review. The Cochrane Risk of bias tool is a checklist used to assess the risk of bias in clinical trials. It aids reviewers in evaluating the validity of included studies and is widely used in systematic reviews and meta-analyses. This tool includes several key domains: Selection, Performance, Detection, Attrition, Reporting, and other sources of bias. Each domain is evaluated to determine the potential risk of bias within the study. Reviewers assign a judgment of “Low risk”, “Unclear risk”, or “High risk” for each domain based on the information provided in the study. Descriptive statistics was used to analyze the data using SPSS software versions 16.

Results

A total of 57 systematic review articles and meta-analyses, encompassing a subset of 509 clinical trials, were studied and evaluated. The analysis of clinical trials included in systematic reviews related to MS Cochrane yielded the following results: Our primary objective was to assess the appropriateness of research questions in these trials. The analysis revealed that all systematic review studies from the Cochrane MS Group posed appropriate research questions. Table 1 provides details related to the objectives of these included studies.

Following this, we assessed the quality of each Cochrane systematic review study using the JBI checklist (Table 2).

The results of this evaluation are presented in Table 3, indicating that all studies met the acceptable quality standards.

In the process of conducting quality reviews of clinical trials under systematic review studies, the most frequently observed risk of bias was a low outcome for Selective Reporting (data reporting), followed by an unclear outcome for allocation concealment (selection bias) (Figures 1 and 2).

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Figure 1.

Evaluating the extent of selection bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

Figure 1.

Evaluating the extent of selection bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

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Figure 2.

Evaluating the extent of selection bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

Figure 2.

Evaluating the extent of selection bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

Conversely, the group of blinding of participants and personnel (performance bias) exhibited the highest risk of bias (Figure 3), while the selective reporting (data reporting) group demonstrated the lowest risk of bias.

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Figure 3.

Evaluating the extent of performance bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

Figure 3.

Evaluating the extent of performance bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

The risk of bias was also evaluated across different time frames. Specifically, the risk of bias was assessed in two distinct periods: up to 2015 and from 2016 to 2023. In the initial period, the most prevalent risk of bias was a low outcome for Selective Reporting (data reporting). However, in the recent years, the most common risk of bias shifted to a low outcome for Random Sequence Generation (selection bias).

Figures 1 to 8 provide a detailed representation of biases across these different time intervals.

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Figure 4.

Evaluating the extent of detection bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

Figure 4.

Evaluating the extent of detection bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

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Figure 5.

Evaluating the extent of attrition bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

Figure 5.

Evaluating the extent of attrition bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

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Figure 6.

Evaluating the extent of performance and detection bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

Figure 6.

Evaluating the extent of performance and detection bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

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Figure 7.

evaluating the extent of repotting bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

Figure 7.

evaluating the extent of repotting bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

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Figure 8.

Evaluating the extent of other possible bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

Figure 8.

Evaluating the extent of other possible bias in trials incorporated into the systematic reviews of the Cochrane multiple sclerosis group

Discussion

The rapid increase in medical journals and articles has brought the structure of articles and research methodology into sharper focus. High-quality research is crucial as it directly impacts healthcare outcomes, influencing public health policies and treatments. Improving the quality and reducing bias in studies can enhance patient care and reduce healthcare costs.

The Cochrane Library, with its 53 review groups, including the Cochrane MS Group, provides a credible information base for medical decision-making. This systematic review, assesses the risk of biases in published RCTs on MS, within the Cochrane Database, known for its rigorous methodology and stringent bias assessment tools.

MS, a common neurological disease causing significant disability in young adults, necessitates high-quality clinical trials and systematic reviews.⁵ The management and treatment of this condition are continually evolving, with many RCTs evaluating interventions efficacy. These RCTs, when systematically reviewed, provide valuable insights that guide clinical decisions and health policies.¹ However, the reliability of these systematic reviews hinges on the quality of the included RCTs. Biases in RCTs can lead to inaccurate conclusions and harmful clinical recommendations, making bias assessment crucial.

Previous studies have highlighted the variability in the quality of systematic reviews across medical fields. For instance, Gagnier and Kellam⁶⁷ questioned the credibility of orthopedic systematic reviews, while another study found that only a small fraction of internal medicine systematic reviews achieved high scores on the AMSTAR scoring system.⁶⁸

Salehi-Pourmehr et al⁶⁹ reviewed Cochrane systematic reviews in urologic cancers, finding that the most common bias was unclear result for selection bias (allocation concealment and random sequence generation). The highest risk of bias was performance bias (blinding of participants and personnel), while the least was attrition bias (selective and incomplete outcome data). They also noted that some biases are decreasing over time, while some others are increasing.

Hajebrahimi et al⁷⁰ examined the quality of systematic review articles in gynecologic cancers and found that the most common biases were unclear result for selection bias (allocation concealment), and performance bias (blinding of participants and personnel). Also, the highest risk of bias was in Blinding participants and personnel (performance bias), and Incomplete outcome data (attrition bias) while, the lowest risk was in Incomplete outcome data (attrition bias) and Random sequence generation (selection bias).

Despite some biases decreasing, others are increasing, and many remain unclear. This indicates that, despite advancements in study quality assessment and the promotion of systematic reviews, achieving ideal quality in clinical studies is still a work in progress.

Our assessment examined various biases, including selection, performance, detection, attrition, and reporting biases, which can compromise the internal validity of an RCT. Using the PRISMA tool, we found that all studies included in this review met the acceptable quality standards according to the JBI criteria. The most common risk of bias was a low result for selective reporting bias, followed by unclear result for allocation concealment (selection bias). The highest risk of bias was in blinding personnel and participants (performance bias), while the lowest was in selective reporting (reporting data). Selection bias, can lead to imbalances between groups. Also performance and detection biases can influence the outcomes. Additionally, attrition bias can skew the results and reporting bias can misrepresent the intervention’s effect.

Our preliminary findings indicate varying degrees of bias across RCTs, emphasizing the need for more rigorous conduct and reporting to minimize biases. This highlights the importance of considering bias risk when interpreting systematic reviews. Given that the current research is limited to Cochrane Library articles, future studies should also examine articles from other databases for various biases.

Conclusion

Based on the results of the current study, the risk of various biases in most studies conducted in recent years in the field of MS has been declining in all three groups: Low, Unclear, and High, compared to previous years. However, it should be noted that part of this issue may be due to the fewer number of articles entered in the study from 2016 onwards compared to the years before that. In conclusion, despite significant enhancements in improving the quality of studies, there is still a far way to achieve the ideal quality.

Competing Interests

The authors state no Competing interests.

Ethical Approval

This systematic review was conducted with a commitment to transparency and integrity. All included studies were selected based on predefined criteria to ensure an unbiased and comprehensive review.

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