meta analysis master thesis

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Ten simple rules for carrying out and writing meta-analyses

Diego a. forero.

1 Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia

2 PhD Program in Health Sciences, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia

Sandra Lopez-Leon

3 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States of America

Yeimy González-Giraldo

4 Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá., Colombia

Pantelis G. Bagos

5 Department of Computer Science and Biomedical Informatics, University of Thessaly, Lamia, Greece

Introduction

In the context of evidence-based medicine, meta-analyses provide novel and useful information [ 1 ], as they are at the top of the pyramid of evidence and consolidate previous evidence published in multiple previous reports [ 2 ]. Meta-analysis is a powerful tool to cumulate and summarize the knowledge in a research field [ 3 ]. Because of the significant increase in the published scientific literature in recent years, there has also been an important growth in the number of meta-analyses for a large number of topics [ 4 ]. It has been found that meta-analyses are among the types of publications that usually receive a larger number of citations in the biomedical sciences [ 5 , 6 ]. The methods and standards for carrying out meta-analyses have evolved in recent years [ 7 – 9 ].

Although there are several published articles describing comprehensive guidelines for specific types of meta-analyses, there is still the need for an abridged article with general and updated recommendations for researchers interested in the development of meta-analyses. We present here ten simple rules for carrying out and writing meta-analyses.

Rule 1: Specify the topic and type of the meta-analysis

Considering that a systematic review [ 10 ] is fundamental for a meta-analysis, you can use the Population, Intervention, Comparison, Outcome (PICO) model to formulate the research question. It is important to verify that there are no published meta-analyses on the specific topic in order to avoid duplication of efforts [ 11 ]. In some cases, an updated meta-analysis in a topic is needed if additional data become available. It is possible to carry out meta-analyses for multiple types of studies, such as epidemiological variables for case-control, cohort, and randomized clinical trials. As observational studies have a larger possibility of having several biases, meta-analyses of these types of designs should take that into account. In addition, there is the possibility to carry out meta-analyses for genetic association studies, gene expression studies, genome-wide association studies (GWASs), or data from animal experiments. It is advisable to preregister the systematic review protocols at the International Prospective Register of Systematic Reviews (PROSPERO; https://www.crd.york.ac.uk/Prospero ) database [ 12 ]. Keep in mind that an increasing number of journals require registration prior to publication.

Rule 2: Follow available guidelines for different types of meta-analyses

There are several available general guidelines. The first of such efforts were the Quality of Reports of Meta-analyses of Randomized Controlled Trials (QUORUM) [ 13 ] and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) statements [ 14 ], but currently, the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) [ 15 ] has been broadly cited and used. In addition, there have been efforts to develop specific guidelines regarding meta-analyses for clinical studies (Cochrane Handbook; https://training.cochrane.org/handbook ), genetic association studies [ 16 ], genome-wide expression studies [ 17 ], GWASs [ 18 ], and animal studies [ 19 ].

Rule 3: Establish inclusion criteria and define key variables

You should establish in advance the inclusion (such as type of study, language of publication, among others) and exclusion (such as minimal sample size, among others) criteria. Keep in mind that the current consensus advises against strict criteria concerning language or sample size. You should clearly define the variables that will be extracted from each primary article. Broad inclusion criteria increase heterogeneity between studies, and narrow inclusion criteria can make it difficult to find studies; therefore, a compromise should be found. Prospective meta-analyses, which usually are carried out by international consortia, have the advantage of the possibility of including individual-level data [ 20 ].

Rule 4: Carry out a systematic search in different databases and extract key data

You can carry out your systematic search in several bibliographic databases, such as PubMed, Embase, The Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and Google Scholar [ 21 ]. Usually, searching in several databases helps to minimize the possibility of failing to identify all published studies [ 22 ]. In some specific areas, searching in specialized databases is also worth doing (such as BIOSIS, Cumulative index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Sociological Abstracts, and EconLit, among others). Moreover, in other cases, direct search for the data is also advisable (i.e., Gene Expression Omnibus [GEO] database for gene expression studies) [ 23 ]. Usually, the bibliography of review articles might help to identify additional articles and data from other types of documents (such as theses or conference proceedings) that might be included in your meta-analysis. The Web of Science database can be used to identify publications that have cited key articles. Adequate extraction and recording of key data from primary articles are fundamental for carrying out a meta-analysis. Quality assessment of the included studies is also an important issue; it can be used for determining inclusion criteria, sensitivity analysis, or differential weighting of the studies. For example the Jadad scale [ 24 ] is frequently used for randomized clinical trials, the Newcastle–Ottawa scale [ 25 ] for nonrandomized studies, and QUADAS-2 for the Quality Assessment of Diagnostic Accuracy Studies [ 26 ]. It is recommended that these steps be carried out by two researchers in parallel and that discrepancies be resolved by consensus. Nevertheless, the reader must be aware that quality assessment has been criticized, especially when it reduces the studies to a single “quality” score [ 27 , 28 ]. In any case, it is important to avoid the confusion of using guidelines for the reporting of primary studies as scales for the assessment of the quality of included articles [ 29 , 30 ].

Rule 5: Contact authors of primary articles to ask for missing data

It is common that key data are not available in the main text or supplementary files of primary articles [ 31 ], leading to the need to contact the authors to ask for missing data. However, the rate of response from authors is lower than expected. There are multiple standards that promote the availability of primary data in published articles, such as the minimum information about a microarray experiment (MIAME) [ 32 ] and the STrengthening the REporting of Genetic Association Studies (STREGA) [ 33 ]. In some areas, such as genetics, in which it was shown that it is possible to identify an individual using the aggregated statistics from a particular study [ 34 ], strict criteria are imposed for data sharing, and specialized permissions might be needed.

Rule 6: Select the best statistical models for your question

For cases in which there is enough primary data of adequate quality for a quantitative summary, there is the option to carry out a meta-analysis. The potential analyst must be warned that in many cases the data are reported in noncompatible forms, so one must be ready to perform various types of transformations. Thankfully, there are methods available for extracting and transforming data regarding continuous variables [ 35 – 37 ], 2 × 2 tables [ 38 , 39 ], or survival data [ 40 ]. Frequently, meta-analyses are based on fixed-effects or random-effects statistical models [ 20 ]. In addition, models based on combining ranks or p -values are also available and can be used in specific cases [ 41 – 44 ]. For more complex data, multivariate methods for meta-analysis have been proposed [ 45 , 46 ]. Additional statistical examinations involve sensitivity analyses, metaregressions, subgroup analyses, and calculation of heterogeneity metrics, such as Q or I 2 [ 20 ]. It is fundamental to assess and, if present, explain the possible sources of heterogeneity. Although random-effects models are suitable for cases of between-studies heterogeneity, the sources of between-studies variation should be identified, and their impact on effect size should be quantified using statistical tests, such as subgroup analyses or metaregression. Publication bias is an important aspect to consider [ 47 ], since in many cases negative findings have less probability of being published. Other types of bias, such as the so-called “Proteus phenomenon” [ 48 ] or “winner’s curse” [ 49 ], are common in some scientific fields, such as genetics, and the approach of cumulative meta-analysis is suggested in order to identify them.

Rule 7: Use available software to carry metastatistics

There are several very user-friendly and freely available programs for carrying out meta-analyses [ 43 , 44 ], either within the framework of a statistical package such as Stata or R or as stand-alone applications. Stata and R [ 50 – 52 ] have dozens of routines, mostly user written, that can handle most meta-analysis tasks, even complex analyses such as network meta-analysis and meta-analyses of GWASs and gene expression studies ( https://cran.r-project.org/web/views/MetaAnalysis.html ; https://www.stata.com/support/faqs/statistics/meta-analysis ). There are also stand-alone packages that can be useful for general applications or for specific areas, such as OpenMetaAnalyst [ 53 ], NetworkAnalyst [ 54 ], JASP [ 55 ], MetaGenyo [ 56 ], Cochrane RevMan ( https://community.cochrane.org/help/tools-and-software/revman-5 ), EpiSheet (krothman.org/episheet.xls), GWAR [ 57 ], GWAMA [ 58 ], and METAL [ 59 ]. Some of these programs are web services or stand-alone software. In some cases, certain programs can present issues when they are run because of their dependency on other packages.

Rule 8: The records and study report must be complete and transparent

Following published guidelines for meta-analyses guarantees that the manuscript will describe the different steps and methods used, facilitating their transparency and replicability [ 15 ]. Data such as search and inclusion criteria, numbers of abstracts screened, and included studies are quite useful, in addition to details of meta-analytical strategies used. An assessment of quality of included studies is also useful [ 60 ]. A spreadsheet can be constructed in which every step in the selection criteria is recorded; this will be helpful to construct flow charts. In this context, a flow diagram describing the progression between the different steps is quite useful and might enhance the quality of the meta-analysis [ 61 ]. Records will be also useful if, in the future, the meta-analysis needs to be updated. Stating the limitations of the analysis is also important [ 62 ].

Rule 9: Provide enough data in your manuscript

A table with complete information about included studies (such as author, year, details of included subjects, DOIs, or PubMed IDs, among others) is quite useful in an article reporting a meta-analysis; it can be included in the main text of the manuscript or as a supplementary file. Software used for carrying out meta-analyses and to generate key graphs, such as forest plots, should be referenced. Summary effect measures, such as a pooled odds ratios or the counts used to generate them, should be always reported, including confidence intervals. It is also possible to generate figures with information from multiple forest plots [ 63 ]. In the case of positive findings, plots from sensitivity analyses are quite informative. In more-complex analyses, it is advisable to include in the supplementary files the scripts used to generate the results [ 64 ].

Rule 10: Provide context for your findings and suggest future directions

The Discussion section is an important scientific component in a manuscript describing a meta-analysis, as the authors should discuss their current findings in the context of the available scientific literature and existing knowledge [ 65 ]. Authors can discuss possible reasons for the positive or negative results of their meta-analysis, provide an interpretation of findings based on available biological or epidemiological evidence, and comment on particular features of individual studies or experimental designs used [ 66 ]. As meta-analyses are usually synthesizing the existing evidence from multiple primary studies, which commonly took years and large amounts of funding, authors can recommend key suggestions for conducting and/or reporting future primary studies [ 67 ].

As open science is becoming more important around the globe [ 68 , 69 ], adherence to published standards, in addition to the evolution of methods for different meta-analytical applications, will be even more important to carry out meta-analyses of high quality and impact.

Funding Statement

YG-G is supported by a PhD fellowship from Centro de Estudios Interdisciplinarios Básicos y Aplicados CEIBA (Rodolfo Llinás Program). DAF is supported by research grants from Colciencias and VCTI. PGB is partially supported by ELIXIR-GR, the Greek Research Infrastructure for data management and analysis in the biosciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Doing a Systematic Review: A Student's Guide

Student resources, chapter 1: carrying out a systematic review as a master's thesis.

What Is The Difference Between A Systematic Review And A Meta-Analysis?

What Is The Difference Between A Narrative Review And A Systematic Review With Narrative Synthesis?

Conducting a meta-analysis for your student dissertation

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• Published: 12 December 2017

Acceptance of a systematic review as a thesis: survey of biomedical doctoral programs in Europe

• Livia Puljak   ORCID: orcid.org/0000-0002-8467-6061 1 , 2 , 3 &
• Damir Sapunar 3  

Systematic Reviews volume  6 , Article number:  253 ( 2017 ) Cite this article

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Systematic reviews (SRs) have been proposed as a type of research methodology that should be acceptable for a graduate research thesis. The aim of this study was to analyse whether PhD theses in European biomedical graduate programs can be partly or entirely based on SRs.

In 2016, we surveyed individuals in charge of European PhD programs from 105 institutions. The survey asked about acceptance of SRs as the partial or entire basis for a PhD thesis, their attitude towards such a model for PhD theses, and their knowledge about SR methodology.

We received responses from 86 individuals running PhD programs in 68 institutions (institutional response rate of 65%). In 47% of the programs, SRs were an acceptable study design for a PhD thesis. However, only 20% of participants expressed a personal opinion that SRs meet the criteria for a PhD thesis. The most common reasons for not accepting SRs as the basis for PhD theses were that SRs are ‘not a result of a PhD candidate’s independent work, but more of a team effort’ and that SRs ‘do not produce enough new knowledge for a dissertation’. The majority of participants were not familiar with basic concepts related to SRs; questions about meta-analyses and the type of plots frequently used in SRs were correctly answered by only one third of the participants.

Conclusions

Raising awareness about the importance of SRs and their methodology could contribute to higher acceptance of SRs as a type of research that forms the basis of a PhD thesis.

Peer Review reports

Systematic reviews (SRs) are a type of secondary research, which refers to the analysis of data that have already been collected through primary research [ 1 ]. Even though SRs are a secondary type of research, a SR needs to start with a clearly defined research question and must follow rigorous research methodology, including definition of the study design a priori, data collection, appraisal of study quality, numerical analyses in the form of meta-analyses and other analyses when relevant and formulation of results and conclusions. Aveyard and Sharp defined SRs as ‘original empirical research’ because they ‘review, evaluate and synthesise all the available primary data, which can be either quantitative or qualitative’ [ 2 ]. Therefore, a SR represents a new research contribution to society and is considered the highest level in the hierarchy of evidence in medicine [ 3 ].

SRs have been proposed as a type of research methodology that should be acceptable as the basis for a graduate research thesis [ 4 , 5 ]. To the best of our knowledge, there are no reports on the acceptance of SRs as the basis for PhD theses. A recent review addressed potential advantages and disadvantages of such a thesis type and presented opposing arguments about the issue [ 5 ]. However, there were no actual data that would indicate how prevalent one opinion is over another with regard to the acceptance of a SR as the primary research methodology for a PhD thesis. The aim of this cross-sectional study was to assess whether a PhD thesis in European biomedical graduate programs can be partly or entirely based on a SR, as well as to explore the attitudes and knowledge of individuals in charge of PhD programs with regard to a thesis of this type.

Participants

The Organization of PhD Education in Biomedicine and Health Sciences in the European System (ORPHEUS) includes 105 institutional members from 40 countries and six associate members from Canada, Georgia, Iran, Kyrgyzstan, Kazakhstan and the USA [ 6 ]. The ORPHEUS encompasses a network of higher education institutions committed to developing and disseminating best practice within PhD training programs in biomedicine, health sciences and public health. ORPHEUS approved the use of their mailing list for the purpose of this study. The mailing list had 1049 contacts. The study authors were not given the mailing list due to data protection and privacy. Instead, it was agreed that ORPHEUS officials would send the survey via email to the mailing list. The General Secretary of the ORPHEUS contacted individuals responsible for PhD programs (directors or deputy directors) among the institutional members, via e-mail, on 5th of July 2016. These individuals were sent an invitation to complete an online survey about SRs as the basis for PhD theses. We invited only individuals responsible for PhD programs (e.g., directors, deputy directors, head of graduate school, vice deans for graduate school or similar). We also asked them to communicate with other individuals in charge of their program to make sure that only one person per PhD program filled out the survey. If there were several PhD programs within one institution, we asked for participation of one senior person per program.

The survey was administered via Survey Monkey (Portland, OR, USA). The survey took 5–10 min to complete. One reminder was sent to the targeted participants 1 month after the first mail.

The ethics committee of the University of Split School of Medicine approved this study, which formed part of the Croatian Science Foundation grant no. IP-2014-09-7672 ‘Professionalism in Health Care’.

Questionnaire

The 20-item questionnaire, designed specifically for this study by both authors (LP and DS), was first tested for face validity and clarity among five individuals in charge of PhD programs. The questionnaire was then modified according to their feedback. The questionnaire included questions about their PhD program; whether PhD candidates are required to publish manuscript(s) before thesis defence; the minimum number of required manuscripts for defending a PhD thesis; the authorship requirements for a PhD candidate with regard to published manuscript(s); whether there is a requirement for a PhD candidate to publish manuscript(s) in journals indexed in certain databases or journals of certain quality, and how the quality is defined; the description about other requirements for defending a PhD thesis; whether a SR partly or fully meets requirements for approval of a PhD thesis in their graduate program; what are the rules related to the use of a SR as the basis for a PhD thesis; and the number of PhD theses based on SRs relative to other types of research methods.

Participants were also asked about their opinion with regard to the main reasons that SRs are not recognised in some institutions as the basis for a doctoral dissertation, and their opinion about literature reviews, using a four-item Likert scale, ranging from ‘agree’ to ‘disagree’, including an option for ‘don’t know’. In the last question, the participants’ knowledge about SR methodology was examined using nine statements; participants had to rate each statement as either ‘correct’, ‘incorrect’, ‘unsure’ or ‘I don’t know’. Finally, participants were invited to leave their email address if they wanted to receive survey results. The survey sent to the study participants can be found in an additional file (Additional file  1 ).

Data analysis

Survey responses were entered into a spreadsheet, checked by both authors and analysed using Microsoft Excel (Microsoft Inc., Redmond, WA, USA). Descriptive data are presented as frequencies and percentages. All raw data and analysed data sets used in the manuscript are available from authors on request. A point-biserial correlation (SPSS, IBM, Chicago, IL, USA) was used to measure the strength of the association between results on the knowledge test (continuous variable) and the attitude towards SRs as the basis for dissertations (dichotomous variable; we used the answer to the following question as this measure: ‘Do you agree that a systematic review, in whole or in part, meets the criteria for a publication on which a doctoral dissertation can be based?’).

Study participants

There are 105 institutions included in the ORPHEUS network. We received a response from 86 individuals representing 68 institutions from 37 countries (65% institutional response rate). There were more respondents than institutions because some institutions have several PhD programs and thus several program directors. Those responders were used as a unit of analysis in the analysis of attitudes and knowledge; institutions were the unit of analysis when analysing criteria for theses. Some of the questionnaires ( n  = 15) were only partly completed. In most cases, the missing data were related to knowledge about SR methodology.

Overview of requirements for a dissertation

Based on the information provided by the graduate program directors, in the majority of the included PhD programs, students were required to publish a research manuscript prepared within their PhD thesis prior to their thesis defence (83%; n  = 64). Among 13 programs (17%) that did not have this requirement, five respondents (38%) indicated that in their opinion their school’s rules related to a PhD thesis should be changed such as to specify that each thesis should be based on work that is already published in a journal.

The minimum number of published manuscripts necessary for the PhD thesis defence was prespecified in 94% ( n  = 60) of the programs that required publication of research manuscripts prior to the thesis defence. In most of the programs (37%; n  = 22), the number of required manuscripts was three or more. Two manuscripts were required in 30% ( n  = 18) and one was required in 33% ( n  = 20) of the programs. In four programs, there was no formal policy on this matter, but there was a strong expectation that the student will have contributed substantially to several manuscripts in peer-reviewed journals.

In most cases, the PhD candidates’ contribution to published manuscripts within the PhD thesis was determined through first authorship. A requirement that a PhD candidate should be the first author on a manuscript(s) that constitutes a PhD thesis was reported in 82% ( n  = 64) of the graduate programs.

In 60% ( n  = 52) of the graduate programs, the quality of the journals where a PhD candidate has to publish research manuscripts as a part of a PhD thesis was defined by the database in which these journals are indexed. The most commonly specified databases were Web of Science (41%; n  = 35) and MEDLINE/PubMed (13%; n  = 11), followed by Science Citation Index, Scopus, Current Contents, a combination of several databases or, in two cases, a combination of journals from a list defined by some governing body.

Systematic reviews as a PhD thesis

SRs, in whole or in part, met the criteria for acceptable research methodology for a PhD thesis in 47% ( n  = 40) of programs, whereas 53% ( n  = 46) of programs specifically stated that they did not accept SRs in this context (Fig.  1 a, b). Among the programs that accepted SRs, theses could be exclusively based on a SR in 42% ( n  = 17) of programs, while in the remaining programs, SRs were acceptable as one publication among others in a dissertation.

a European PhD programs that recognise a systematic review as a PhD thesis (green dot) and those that do not (red dot). Half red and half green dots indicate the five universities with institutions that have opposite rules regarding recognition of a systematic review as a PhD thesis. The pie chart presents b the percentage of the programs in which systematic reviews, in whole or in part, meet the criteria for a dissertation and c the opinion of participants about whether systematic reviews should form the basis of a publication within a PhD dissertation

The majority of participants (80%; n  = 69) indicated that SRs did not meet criteria for a publication on which a PhD dissertation should be based (Fig.  1 c). The main arguments for not recognising a SR as the basis for a PhD thesis are listed in Table  1 . The majority of respondents were neutral regarding the idea that scoping reviews or SRs should replace traditional narrative reviews preceding the results of clinical and basic studies in doctoral theses. Most of the respondents agreed that narrative or critical/discursive literature reviews preceding clinical studies planned as part of a dissertation should be replaced with systematic reviews (Table  2 ).

Most of the programs that accepted SRs as a research methodology acceptable for PhD theses had defined rules related to the use of an SR as part of a PhD thesis (Fig.  2 ). The most common rule was that a SR can be one publication among others within a PhD thesis. Some of the respondents indicated that empty (reviews that did not find a single study that should be included after literature search) or updated reviews could also be used for a PhD thesis (Fig.  2 ).

Frequency of different rules that define the use of systematic reviews as a part of a PhD thesis in European biomedical graduate programs

The results of the survey regarding knowledge about SR methodology indicated that the majority of respondents were not familiar with this methodology. Only three out of nine questions were correctly answered by more than 80% of the participants, and questions about meta-analyses and the type of plots frequently used in a SR were correctly answered by only one third of the participants (Table  3 ). The association between participants’ results on the knowledge test and attitudes towards SRs was tested using a point-biserial correlation; this revealed that lack of knowledge was not correlated with negative attitudes towards SRs ( r pb  = 0.011; P  = 0.94).

In this study conducted among individuals in charge of biomedical graduate programs in Europe, we found that 47% of programs accepted SRs as research methodology that can partly or fully fulfil the criteria for a PhD thesis. However, most of the participants had negative attitudes about such a model for a PhD thesis, and most had insufficient knowledge about the basic aspects of SR methodology. These negative attitudes and lack of knowledge likely contribute to low acceptance of SRs as an acceptable study design to include in a PhD thesis.

A limitation of this study was that we relied on participants’ responses and not on assessments of formal rules of PhD programs. Due to a lack of familiarity with SRs, it is possible that the respondents gave incorrect answers. We believe that this might be the case since we received answers from different programs in the same university, where one person claimed that SRs were accepted in their program, and the other person claimed that they were not accepted in the other program. We had five such cases, so it is possible that institutions within the same university have different rules related to accepted research methodology in graduate PhD programs. This study may not be generalisable to different PhD programs worldwide that were not surveyed. The study is also not generalisable to Europe, as there are no universal criteria or expectations for PhD theses in Europe. Even in the same country, there may be different models and expectations for a PhD in different higher education institutions.

A recent study indicated a number of opposing views and disadvantages related to SRs as research methodology for graduate theses, including lack of knowledge and understanding by potential supervisors, which may prevent them from being mentors and assisting students to complete such a study [ 5 ]. This same manuscript emphasised that there may be constraints if the study is conducted in a resource-limited environment without access to electronic databases, that there may be a very high or very low number of relevant studies that can impact the review process, that methods may not be well developed for certain types of research syntheses and that it may be difficult to publish SRs [ 5 ].

Some individuals believe that a SR is not original research. Indeed, it has been suggested that SRs as ‘secondary research’ are different than ‘primary or original research’, implying that they are inferior and lacking in novelty and methodological rigour as compared to studies that are considered primary research. In 1995, Feinstein suggested that such studies are ‘statistical alchemy for the 21st century’ and that a meta-analysis removes or destructs ‘scientific requirements that have been so carefully developed and established during the 19th and 20th centuries’ [ 7 ]. There is little research about this methodological issue. Meerpohl et al. surveyed journal editors and asked whether they consider SRs to be original studies. The majority of the editors indicated that they do think that SRs are original scientific contributions (71%) and almost all journals (93%) published SRs. That study also highlighted that the definition of original research may be a grey area [ 8 ]. They argued that, in an ideal situation, ‘the research community would accept systematic reviews as a research category of its own, which is defined by methodological criteria, as is the case for other types of research’ [ 8 ]. Biondi-Zoccai et al. pointed out that the main criteria to judge a SR should be its novelty and usefulness, and not whether it is original/primary or secondary research [ 9 ].

In our study, 80% of the participants reported negative attitudes, and more than half of the respondents agreed with a statement that SRs are ‘not a result of the candidate’s independent work since systematic reviews tend to be conducted by a team’. This opinion is surprising since other types of research are also conducted within a team, and single authorship is very rare in publications that are published within a PhD thesis. On the contrary, the mean number of authors of research manuscripts is continuously increasing [ 10 ]. At the very least, the authors of manuscripts within a PhD will include the PhD candidate and a mentor, which is a team in and of itself. Therefore, it is unclear why somebody would consider it a problem that a SR is conducted within a team.

The second most commonly chosen argument against such a thesis was that SRs ‘do not produce enough new knowledge for a dissertation’. The volume of a SR largely depends on the number of included studies and the available data for numerical analyses. Therefore, it is unfair to label a SR as a priori lacking in new knowledge. There are SRs with tens or hundreds of included studies, and some of them not only include meta-analyses, but also network meta-analyses, which are highly sophisticated statistical methods. However, limiting SRs within a thesis only to those with meta-analysis would be unfair because sometimes meta-analysis is not justified due to clinical or statistical heterogeneity [ 11 ] and the presence or absence of a meta-analysis is not an indicator of the quality of a SR. Instead, there are relevant checklists for appraising methodological and reporting quality of a SR [ 12 , 13 ].

The third most commonly chosen argument against SRs within PhD theses was ‘lack of adequate training of candidates in methodology of systematic reviews’. This could refer to either insufficient formal training or insufficient mentoring. The graduate program and the mentor need to ensure that a PhD candidate receives sufficient knowledge to complete the proposed thesis topic. Successful mentoring in academic medicine requires not only commitment and interpersonal skills from both the mentor and mentee, but also a facilitating institutional environment [ 14 ]. This finding could be a result of a lack of capacity and knowledge for conducting SRs in the particular institutions where the survey was conducted, and not general opinion related to learning a research method when conducting a PhD study. Formal training in skills related to SRs and research synthesis methods [ 15 , 16 ], as well as establishing research collaborations with researchers experienced in this methodology, could alleviate this concern.

One third of the participants indicated a ‘lack of appreciation of systematic review methodology among faculty members’ as a reason against such a thesis model. This argument, as well as the prevalent negative attitude towards SRs as PhD theses, perhaps can be traced to a lack of knowledge about SR methodology; however, although the level of knowledge was quite low in our study, there was no statistically significant correlation between knowledge and negative attitudes. Of the nine questions about SR research methodology, only three questions were correctly answered by more than half of the participants. This could be a cause for concern because it has been argued that any health research should begin with a SR of the literature [ 17 ]. It has also been argued that the absence of SRs in the context of research training might severely hamper research trainees and may negatively impact the research conducted [ 18 ]. Thus, it has been recommended that SRs should be included ‘whenever appropriate, as a mandatory part of any PhD program or candidature’ [ 18 ].

It has recently been suggested that the overwhelming majority of investment in research represents an ‘avoidable waste’ [ 19 ]. Research that is not necessary harms both the public and patients, because funds are not invested where they are really necessary, and necessary research may not be conducted [ 17 ]. This is valid not only for clinical trials, but also for other types of animal and human experiments [ 20 ]. SRs can help improve the design of new experiments by relying on current evidence in the field and by helping to clarify which questions still need to be addressed. SRs can be instrumental in improving methodological quality of new experiments, providing evidence-based recommendations for research models, reducing avoidable waste, and enabling evidence-based translational research [ 20 ].

Four respondents from three institutions indicated that empty SRs are accepted as a PhD thesis. While it makes sense to include such a SR as a part of the thesis to indicate lack of evidence in a certain field, it is highly unlikely that an entire thesis can be based on an empty SR, without a single included study.

There are many advantages of a SR as a graduate thesis [ 4 , 5 ], especially as a research methodology suitable for low-resource settings. A PhD candidate can prepare a Cochrane SR as a part of the PhD thesis, yielding a high-impact publication [ 4 ]. Non-Cochrane SRs can also be published in high-impact journals. A PhD candidate involved in producing a SR within a PhD thesis goes through the same research process as those conducting primary research, from setting up a hypothesis and a research question, to development of a protocol, data collection, data analysis and appraisal, and formulation of conclusions. Graduate programs can set limits, such as the prevention of empty reviews and the recognition of updated reviews as valid for a PhD thesis, and engage experienced researchers as advisors and within thesis evaluation committees, to ensure that a candidate will conduct a high-quality SR [ 4 ]. Conducting a SR should not be mandatory, but candidates and mentors willing to produce such research within a graduate program should be allowed to do so.

Further studies in this field could provide better insight into attitudes related to SRs as graduate theses and explore interventions that can be used to change negative attitudes and improve knowledge of SRs among decision-makers in graduate education.

Raising awareness about the importance of SRs in biomedicine, the basic aspects of SR methodology and the status of SRs as original secondary research could contribute to greater acceptance of SRs as potential PhD theses. Our results can be used to create strategies that will enhance acceptance of SRs among graduate education program directors.

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Acknowledgements

The authors thank the ORPHEUS secretariat for administering the survey and the study participants for taking time to participate in the survey. We are grateful to Prof. Ana Marušić for the critical reading of the manuscript.

This research was funded by the Croatian Science Foundation, grant no. IP-2014-09-7672 ‘Professionalism in Health Care’. The funder had no role in the design of this study or its execution and data interpretation.

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Puljak, L., Sapunar, D. Acceptance of a systematic review as a thesis: survey of biomedical doctoral programs in Europe. Syst Rev 6 , 253 (2017). https://doi.org/10.1186/s13643-017-0653-x

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A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER)

Affiliations.

• 1 Department of Radiation Oncology, University of California, Los Angeles, CA, USA.
• 2 Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
• 3 Department of Medicine, Statistics Core, University of California, Los Angeles, CA, USA.
• 4 Department of Urology, Mayo Clinic, Rochester, MN, USA.
• 5 Department of Urology, University of California, Los Angeles, CA, USA.
• 6 Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Division of Hematology and Oncology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
• 7 Ahmanson Translational Theranostics Division, Department of Molecular & Medical Pharmacology, University of California, Los Angeles, CA, USA.
• 8 Department of Radiation Oncology, University of California, Los Angeles, CA, USA; Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
• 9 Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
• 10 Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
• 11 Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
• 12 Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA.
• 13 Department of Radiation Oncology, University of California, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, CA, USA. Electronic address: [email protected].
• PMID: 33309278
• PMCID: PMC10262981
• DOI: 10.1016/j.eururo.2020.11.010

Context: Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality.

Objective: To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy.

Evidence acquisition: We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities.

Evidence synthesis: A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified.

Conclusions: Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted.

Patient summary: In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.

Keywords: Cryotherapy; High-dose-rate brachytherapy; High-intensity focused ultrasound; Low–dose-rate brachytherapy; Meta-analysis; Prostate cancer; Radiation therapy; Radical prostatectomy; Radiorecurrent prostate cancer; Salvage therapy; Stereotactic body radiotherapy.

Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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(A–F) Forest plots showing…

(A–F) Forest plots showing individual study values of 2-yr RFS estimates for…

(A–E) Forest plots showing…

(A–E) Forest plots showing individual study values of 5-yr RFS estimates for…

(A–F) Forest plots showing individual study values of severe GU toxicity estimates…

(A–F) Forest plots showing individual study values of severe GI toxicity estimates…

• Reply to Sungeun Kim, Jae Il Shin, and Jonathan Evan Shoag's Letter to the Editor re: Luca F. Valle, Eric J. Lehrer, Daniela Markovic, et al. A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER). Eur Urol. In press. https://doi.org/10.1016/j.eururo.2020.11.010. Valle LF, Kishan AU. Valle LF, et al. Eur Urol. 2021 Jul;80(1):e15-e16. doi: 10.1016/j.eururo.2021.04.010. Epub 2021 Apr 29. Eur Urol. 2021. PMID: 33934928 No abstract available.
• Re: Luca F. Valle, Eric J. Lehrer, Daniela Markovic, et al. A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER). Eur Urol. In press. https://doi.org/10.1016/j.eururo.2020.11.010. Kim SE, Shin JI, Shoag JE. Kim SE, et al. Eur Urol. 2021 Jul;80(1):e14. doi: 10.1016/j.eururo.2021.04.011. Epub 2021 Apr 30. Eur Urol. 2021. PMID: 33941402 No abstract available.
• Mastering the Landscape of Postradiation Local Prostate Salvage Therapy. Zheng J, Crook J. Zheng J, et al. Eur Urol. 2021 Sep;80(3):293-294. doi: 10.1016/j.eururo.2021.04.032. Epub 2021 May 15. Eur Urol. 2021. PMID: 34006445 No abstract available.

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Women’s Leadership Dilemma: Why Ethiopian Women in Academia Prefer to Stay away from Decision-Making?

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• Published: 21 August 2024

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• Tesfaye Semela   ORCID: orcid.org/0000-0001-8937-898X 1 , 2 &
• Sintayehu Hailu   ORCID: orcid.org/0000-0001-9341-8219 2  

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Notwithstanding the growing visibility in political and administrative positions, women are not sufficiently represented in higher education leadership in Ethiopia. The present study attempts to unravel why women do not take up leadership against the backdrop of “female leadership advantage’’ and favourable policy environment that purportedly exist. Based on re-analysis of secondary quantitative data and an in-depth interview with 20 current and former female academic leaders, it is found that more and more women in academia are less willing to take up leadership roles. Furthermore, the study is unable to confirm the widely advertised political will and policy promises to ensure gender inclusion in higher academic leadership due to the erratic trends of gender balance over the past half a decade.

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Semela, T., Hailu, S. Women’s Leadership Dilemma: Why Ethiopian Women in Academia Prefer to Stay away from Decision-Making?. High Educ Policy (2024). https://doi.org/10.1057/s41307-024-00371-2

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Published : 21 August 2024

DOI : https://doi.org/10.1057/s41307-024-00371-2

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