This qualitative study investigates factors that may impede or facilitate inclusion of systematic evidence assessments in academic clinical trials using interviews with Swiss stakeholders and international funders. What are the practices and attitudes of Swiss stakeholders and international funders regarding conducting systematic evidence assessments in academic clinical trials?In this qualitative study in which 48 Swiss clinical trial stakeholders and 9 international funders were interviewed, responses varied widely regarding how previous evidence should be summarized and assessed when planning a new clinical trial. A lack of obligation, time, competent support, and financial resources was identified as a barrier for an evidence-based approach.There may be a need for more explicit requirements from funders and ethics committees to clarify the level of comprehensiveness needed in summarizing existing evidence for different types of clinical trials. A systematic assessment of existing research should justify the conduct and inform the design of new clinical research but is often lacking. There is little research on the barriers to and factors facilitating systematic evidence assessments.To examine the practices and attitudes of Swiss stakeholders and international funders regarding conducting systematic evidence assessments in academic clinical trials.In this qualitative study, individual semistructured qualitative interviews were conducted between February and August 2020 with 48 Swiss stakeholder groups  and between January and March 2021 with 9 international funders of clinical trials from North America and Europe with a reputation for requiring systematic evidence synthesis in applications for academic clinical trials.The main outcomes were practices and attitudes of Swiss stakeholders and international funders regarding conducting systematic evidence assessments in academic clinical trials. Interviews were analyzed using conventional content analysis.Of the 57 participants, 40 (70.2%) were male. Participants universally acknowledged that a comprehensive understanding of the previous evidence is important but reported wide variation regarding how this should be achieved. Participants reported that the conduct of formal systematic reviews was currently not expected before most clinical trials, but most international funders reported expecting a systematic search for the existing evidence. Whereas time and resources were reported by all participants as barriers to conducting systematic reviews, the Swiss research ecosystem was reported not to be as supportive of a systematic approach compared with international settings.In this qualitative study, Swiss stakeholders and international funders generally agreed that new clinical trials should be justified by a systematic evidence assessment but that barriers on individual, organizational, and political levels kept them from implementing it. More explicit requirements from funders appear to be needed to clarify the required level of comprehensiveness in summarizing existing evidence for different types of clinical trials. Verbal informed consent was obtained from participants at the start of the interview. The study followed the Consolidated Criteria for Reporting Qualitative Research . Additional participants were identified using snowball sampling.36 Participants were contacted by email and suitable dates for an interview were found with those willing to participate. The study consisted of 57 participants from 2 different samples. In the first sample, 48 Swiss stakeholders from 4 different groups were recruited: 27 primary investigators, 9 funders and sponsors, 6 clinical trial support organizations, and 6 ethics committee members. In the second sample, 9 international funders from North America and Europe with a reputation for implementing an evidence-based approach for clinical trials were recruited.24 Interviews were conducted between February and August 2020 with Swiss stakeholders and between January and March 2021 with international funders. One participant provided their response in writing via email; the remaining interviews were conducted via a telephone or video call. All interviews were conducted in English. Only the participant and the researcher were present during the interview. A researcher-developed semistructured interview guide was created for each group to guide the discussion . Analysis commenced while interviews were ongoing and used an iterative approach in which initial codes common across participants as well as those unique to individuals were identified using a process of open coding and developed as the analysis progressed. B.N.-S., L.G.H., and M.B. reviewed the initial analysis to clarify and refine codes, and conversations among the investigators continued until coding differences were resolved and consensus was achieved. Findings are presented as higher- and lower-level categories in a coding frame.Of the 57 participants, 40 (70.2%) were male. Swiss participants universally acknowledged the importance of having a comprehensive understanding of the previous evidence when designing and justifying a new clinical trial. However, it was reported that most investigators in Switzerland were not currently conducting systematic reviews, and it was estimated that systematic reviews only happened in 10% to 30% of trials. Many participants disagreed that systematic reviews were always necessary before a new clinical trial and reported that the need for a systematic review depended on the type of clinical trial and available evidence. Only a few participants said a systematic review should always be done before a new clinical trial if no systematic review had been recently published on the topic by other researchers .In contrast, international funders reported a clear expectation that academic clinical trial proposals should include some form of systematic evidence synthesis . HoweverThe level of comprehensiveness that participants expected in summaries of existing evidence typically depended on the type of clinical trials being funded. A funder of large, late-stage multicenter clinical trials reported that they expected a formal systematic review to be provided; this was seen as important owing to the focus on public funding and accountability in their country, with systematic reviews being a part of opening the scientific process to public scrutiny. However, most funders of smaller, earlier-stage clinical trials reported that they did not mandate formal systematic reviews and only required a systematic search of the literature (including the search strategy and databases used). Nevertheless, 2 international funders who were members of the Ensuring Value in Research Funders’ Forum reported that they did not have explicit requirements regarding evidence assessment and left it to investigators what to provide.Most funders reported having a 2-step funding process. Although 1 funder required systematic evidence assessments to be provided at the preapplication stage, most funders required it at the full application stage. Participants from the latter group reported that the key reason for requesting the evidence assessment at the second step was the limited space available in preapplications and the desire to reduce the work of the funder and the applicants who would not be funded.Swiss participants identified 3 key barriers that may explain why systematic reviews are used infrequently.The first barrier was investigator perceptions. Participants reported that various views of principal investigators led them to not conduct systematic reviews before a new trial, including the view that they were experts in the field and already knew the relevant research; the view that their study was very innovative, and therefore, a systematic review did not make sense because of the limited evidence available; and the belief that an evidence-based approach could be achieved without a formal systematic review.The second barrier was practical challenges. Some practical challenges were also identified by participants as reasons why systematic reviews were not conducted, including systematic reviews being very time consuming; a lack of specific funds, which led to systematic reviews often being done without funding; insufficient personnel with the right expertise to conduct systematic reviews; and a lack of awareness and knowledge of systematic reviews among investigators and funding panels.The third barrier was lack of enforcement. Participants also reported that none of the funders of academic clinical trials in Switzerland were currently requiring a systematic review, that the method for reviewing the existing research was left to principal investigators, and that funders relied on the expertise of reviewers to evaluate whether the information presented in applications was sufficient. Participants also reported that ethics committees did not require systematic reviews and that although ethics committees checked whether the literature review conducted was generally sufficient and might ask for more information if the review was clearly inadequate, they ultimately saw this as the responsibility of the principal investigator and outside the task of ethics committees.International funders did not report perceiving substantial barriers. Investigators were seen to have sufficient awareness and knowledge and generally accepted the funder’s expectations regarding evidence assessment. The practical challenges of time and resources were identified as the main barriers to formal systematic reviews. Because formal systematic reviews were perceived as time consuming and typically unfunded, these participants reported that mandating them could create problems and undermine innovative research. However, a funder of larger clinical trials noted that if an investigator was applying for a substantial sum of money to run a large multicenter clinical trial, they would expect the investigator to have the resources to do this sort of preparatory work.Many Swiss participants reported that the best way to facilitate systematic evidence assessments was for funders to make them mandatory. Although participants said they wanted such a requirement to be feasible and flexible, many reported that funders were the most suitable stakeholder to enforce evidence assessments and said that knowing what the current evidence is for a research question should be a prerequisite for academic clinical trials, particularly if large amounts of public funds are involved. However, many participants also acknowledged that any such requirement would need to be combined with better support from academic institutions and associated clinical trial support organizations.In contrast, multiple international funders highlighted how evidence assessment communities had become firmly established in their countries, with sufficient capacity now existing for training, expertise, and collaboration, which had been important in promoting a systematic approach. Moving forward, some funders said that it would be helpful to provide investigators with more explicit requirements to clarify the level of comprehensiveness expected. However, funders identified a need to improve their own knowledge of the different types of evidence assessment  and for more research on the advantages and disadvantages of each approach.To our knowledge, this is the first qualitative study to examine the barriers to and factors facilitating an evidence-based research approach with several stakeholders in the context of academic clinical trials. This study found general agreement among Swiss stakeholders and international funders that new clinical trials should be justified by a systematic evidence assessment, but there seemed to be substantial variation among stakeholders in terms of the expected comprehensiveness and transparency of evidence assessments. Formal systematic reviews are currently not expected and not conducted before most clinical trials, but most international funders expect a systematic search for the existing evidence. Whereas time and resources were reported by all participants as barriers to conducting systematic reviews, the Swiss research ecosystem was reported not to be as supportive of a systematic approach compared with international settings. Moving toward a more evidence-based research approach in academic clinical trials requires changes on multiple levels.39 In addition, it seems necessary to raise awareness within the scientific community that expert opinion and narrative reviews are not enough to implement evidence-based research. They have a high risk of being distorted by confirmation bias—the tendency to search and interpret information in a way that supports one’s own beliefs—and therefore are not sufficient to foster transparent evidence-based research.40On an individual level, we identified a lack of awareness and knowledge of the importance of systematic reviews as well as a lack of skills to conduct systematic reviews. Providing training and integrating courses into the curricula of life sciences to build capacity in evidence-based research as well as more support from academic institutions  could help to overcome these barriers.41 Rapid reviews, “a form of knowledge synthesis that accelerates the process of conducting a traditional systematic review through streamlining or omitting specific methods to produce evidence for stakeholders in a resource-efficient manner,”42 have emerged as pragmatic alternatives to systematic reviews and could enable primary researchers to sustainably adopt an evidence-based approach.44 Conducting a systematic review is  a prerequisite during the application stage, meaning that the update or conduct of a systematic review is often not funded. Thus, researchers may opt to apply for a clinical trial grant without putting unpaid resources into the production of a systematic review. Funders could consider financially supporting the production of systematic reviews or providing grant application funds. Although this might cost money initially, it could save money and resources by avoiding research waste in the long run.At an organizational level, resource constraints  often hinder the conduct of comprehensive systematic reviews. Conducting a comprehensive systematic review can take up to 1 to 2 years.17 For smaller, earlier-stage clinical trials, funders could also explicitly clarify the requirements with respect to a systematic evidence assessment . Ethics committees have also been called on to more vigorously advocate for an evidence-based approach.45On a political level, the lack of funders and ethics committees requiring systematic reviews was perceived by the study participants as a barrier. Making systematic evidence assessments mandatory for funding and ethics approval emerged as the most promising factor to facilitate implementation of evidence-based research. According to the National Institutes of Health Research in the UK, specifically requiring systematic reviews to justify the need for a new large multicenter trial can increase their use to nearly 100%.46 or they specifically focused on a survey of methodologists on their opinions about a conditional trial design framework using network meta-analysis for the planning of new trials.47 The current study contributes to the findings of the preliminary survey of methodologists by Clayton et al18 by including perceptions of various stakeholders outside the UK and Ireland and by conducting in-depth interviews, which resulted in a more thorough understanding of barriers to and factors facilitating an evidence-based approach when designing a new trial.This study fills a research gap because, to our knowledge, other studies generally investigated the “natural history of conducting and reporting clinical trials” in interviews, with trialists only touching on “insufficient reference to previous research” when planning a new trial,48 Given that the results were critical of current practice, we believe such a bias is limited. Third, with the exception of funders, all participants were from Switzerland, compromising the generalizability of the findings to some degree. However, the findings are generally in line with existing research,18 and probing current practices of funders from different countries that have the reputation of endorsing an evidence-based approach and contrasting their views with Swiss stakeholders has yielded rich findings about knowledge gaps and insufficient clarity of funder requirements regarding evidence assessments. There appear to be a number of common issues across countries, which likely make our findings of interest to many countries.This study has limitations. First, this qualitative study did not use a random sample of stakeholders. However, we included a range of experts who had direct experience with systematic evidence assessment in academic clinical trials, which makes it likely that this study captured key aspects of a multisided issue and provided applicable results. Second, a bias might have existed toward the reporting of socially desirable attitudes.45 In addition, universities should train students and researchers in evidence-based methods and raise awareness of the importance of a systematic and transparent approach to justify new trials.In this qualitative study, there was general agreement among Swiss stakeholders and international funders that new clinical trials should be justified by a systematic evidence assessment. However, investigators reported that barriers on individual, organizational, and political levels still regularly kept them from implementing these assessments. In their role as gatekeepers, funding agencies and ethics committees are in a position to enforce an evidence-based research approach by making it mandatory for new clinical trials.


Guidelines are the product of an explicit, systematic approach to the evaluation and synthesis of available information on a particular clinical topic. They are not a compilation of truths, but are a summary of what is accepted by the authors as the best available evidence at that time’ [Sepsis is a major cause of death worldwide, not least because complex interventions need to be provided within a short window of opportunity. Evidence-based guidelines for the treatment of sepsis are therefore welcome, providing a common ground for all clinicians involved in decision-making regardless of their expertise. Such guidelines should therefore serve as an overarching reference document. As previously stated, ‘at time’ .As the evidence base evolves over time, the new Surviving Sepsis Campaign (SSC) guidelines  are timeintensive to adopt a generalized approach, yet customization is surely the underlying foundation of intensive care. When we forget the fundamental importance of individualized management, the ultimate result is that few interventions improve meaningful patient outcomes, especially mortality [“Good doctors use both individual clinical expertise and the best available external evidence, and neither alone is enough. Without clinical expertise, practice risks becoming tyrannised by evidence, for even excellent external evidence may be inapplicable to or inappropriate for an individual patient. Without current best evidence, practice risks becoming rapidly out-of-date, to the detriment of patients.” [.The most severely ill patients usually suffer less from a single condition than from a complex physiological imbalance that defies specific disease definitions. Management that strictly adheres to guidelines may not necessarily be the best option. However, personalizing management of these patients mandates that the treating clinician appreciates the clinical implications of the underlying disease(s) and individual host factors . Additionally, the individual response to interventions must be closely monitored and, depending on that response and whether or not the pre-set goal of that intervention has been achieved, the clinician can then decide to maintain or alter the intervention accordingly. We fully acknowledge this is demanding in resources, time, personnel, and bedside expertise. It is more convenient and less labor-ortality . We musttients.” .The conundrum is how to encourage guideline implementation yet at the same time promote personalized medicine. The new guidelines  offer liWe have therefore taken the liberty of putting forward some proposals of how guidelines could be adapted to individualize care Table . We fullEvidence based medicine is not "cookbook" medicine. (…) External clinical evidence can inform, but can never replace, individual clinical expertise, and it is this expertise that decides whether the external evidence applies to the individual patient at all and, if so, how it should be integrated into a clinical decision.” [one size does not fit all”.The way forward is to be bold enough to question how we can do better. It may be time to move from a mass approach, based on pragmatic studies performed on heterogeneous populations, to tailored studies allowing both dissection and integration of the information collected in specific sepsis phenotypes. We need to embrace theragnostic approaches, using biomarkers to identify only those patients for whom the intervention is suited, and to titrate dose and duration to optimal effect. Crucially, we need to restore the application of physiology and biochemistry to the forefront of our clinical practice. Returning to Sackett: “cision.” . Sepsis


Forensic entomologists are most often tasked with determining when arthropods colonized living or deceased vertebrates. In most cases, this estimation involves humans; however, pets, livestock, and other domesticated animals can also be illegally killed or victims of neglect. Globally, there is no standard format for the case report, and much of the content is based on the personal preferences of the analyst or standards set within a country. The article below proposes a general overview of sections to be considered when drafting a case report.Forensic practitioners analyzing entomological evidence are faced with numerous challenges when presenting their findings to law practitioners, particularly in terms of terminology used to describe insect age, what this means for colonization time of remains, and the limitations to estimates made. Due to varying legal requirements in different countries, there is no standard format for the entomological case report prepared, nor any guidelines as to the sections that are required, optional or unnecessary in a case report. The authors herein propose sections that should be considered when drafting an entomological case report. The criteria under which entomological evidence is analyzed are discussed, as well as the limitations for each criterion. The concept of a global, standardized entomological case report is impossible to achieve due to national legislative differences, but the authors here propose a basic template which can be adapted and changed according to the needs of the practitioner. Furthermore, while the discussion is fairly detailed, capturing all differences between nations could not be accomplished, and those initiating casework for the first time are encouraged to engage other practicing forensic entomologists or professional associations within their own nation or region, to ensure a complete report is generated that meets lab or national requirements, prior to generating a finalized report. In the last ~20 years, developments in the field of forensic entomology have progressed greatly and at pace. These increased research efforts and applications have resulted in over 1100 research and review articles, and books, published since 2000 . Of courDue to such standards being in place in most parts of the world, efforts have been aimed at developing specific guidelines for forensic entomology. Accreditation standards, such as those implemented by the European Association for Forensic Entomology (EAFE) for the sampling and evaluation of entomological traces, and the certification of entomological experts by the American Board of Forensic Entomology (ABFE), as well as the accreditation of laboratories  , have alForensic entomologists are often tasked with determining “how long the victim has been dead” by law enforcement and other officials , and mayThe overarching principle of forensic entomology is based on the arrival of insects to remains shortly after death, whereafter eggs or larvae are deposited. Larvae develop on the remains, and the age of the oldest developmental stages can be determined when the remains are discovered . AssuminEnvironmental weather records in the area reflect those at the body, and thus directly affect the development of the arthropods present:The consideration of temperature is fundamental in estimating the age of insects ,8. The mPublished developmental datasets based on laboratory studies accurately reflect developmental patterns in the nature of the insect evidence collected:The vast majority of published and accepted insect developmental datasets have been derived under laboratory conditions. These conditions usually applied a range of temperature profiles (constant or with daily variations), controlled humidity and specified light: dark cycles. When developing in a natural environment, none of the above-mentioned factors are controlled, and can affect development accordingly ,11,12. TColonization occurred after death :In certain situations, oviposition or larviposition may occur before death, for example, when the decedent has open and possibly necrotic wounds such as decubitus ulcers (bed sores). Myiasis is the colonization of a living vertebrate host by fly larvae , and if Specimens collected and analyzed developed on the body of the victim:Contamination of insect evidence can occur from other organisms that are deceased and within close proximity of the remains under scrutiny. For example, in an outdoor case, empty puparia in soil samples from a crime scene could originate from flies that had developed on a dead animal in the immediate vicinity at an earlier time. Carrion-colonizing Diptera are diurnal and do not usually oviposit at night:Nocturnal oviposition is very rare and is thus usually excluded from analyses. Historically, it was assumed that oviposition only occurs during the day and, thus, hours of darkness were not considered when estimating the minPMI based on calculating the time of oviposition ,20,21. Carrion-colonizing insects  have free access to the body:Oviposition or larviposition on the deceased occurs shortly after death without hindrance . However, in medico-legal cases where entomological evidence is to be obtained, a decedent may be concealed in order to prevent law enforcement from finding the body. This concealment may include burial, wrapping or disposal in bodies of water. In such instances, carrion-colonizing arthropods are limited in their access to the remains, often only gaining access after the remains have been discovered or exposed by the elements or by scavengers. In such instances particularly, the entomological evidence obtained provides details regarding the period of environmental exposure, provided the remains have always been in the conditions of their discovery, but cannot provide more specific information regarding a time frame of the decedents’ death.Faunal succession patterns on, in and under the body can be used in estimating colonization intervals:While faunal succession patterns are somewhat predictable , they arDue to the ectothermic nature of insects, much of their physiology, ecology, and behavior has been documented in relation to environmental conditions, especially temperature, but also including humidity, light intensity and wind. Insects inhabiting carrion, which include mainly flies  and beetles , have been extensively studied and various criteria have been set forth to evaluate their development and succession on remains for a forensic report. The author of a forensic report should never assume  anything; nevertheless, there are certain criteria related to insect biology which have support from scientific study and can act as guides to an analysis of insect evidence, unless there is compelling evidence to the contrary. Some of the basic criteria used by forensic practitioners, as well as their limitations, are listed below :EnvironWhile the above criteria and limitations are broadly applicable to most cases, it must be noted that each case containing entomological evidence is unique and should be analyzed accordingly—there is no “one size fits all” approach.There have been some disputes in recent years regarding the terminology used by forensic practitioners concerning entomological evidence . HistoriA myriad of alternative terms has been introduced to describe the activity of arthropods on remains. In some manner or another, each term that is used describes the time since arthropods have colonized the remains. The terms include: minPMI; post-colonization interval (PCI); and time of colonization (TOC) ,34.Irrespective of the terminology selected by the practitioner, it is critical that the reader understands what the term used in the report is referring to and what it means; namely, a period of time which has passed at least since the occurrence of death. The clarification of terms is important for interpretation of the report by individuals without entomological/scientific training, such as law practitioners or judges/jurors. Numerous dichotomous and pictographic keys exist for the identification of arthropods based on physical characteristics. These keys are still the most frequently used means of identification for both immature and adult specimens of forensic importance. In many instances, samples may be received by the practitioner that have been damaged or are missing body parts. In such situations, the use of a dichotomous or pictographic key may not be the best avenue, as these keys reference specific body regions. Resources such as Lucidcentral  allow foLucilia cuprina (Wiedemann) and L. sericata (Meigen) [Hemilucilia segmentaria (Fabricius) and H. semidiaphana (Rondani)  [With the advent of molecular identification techniques, such as DNA barcoding, arthropod identification, especially that of insect fragments, has become easier ,38,39,40(Meigen) , or Hemihoridae) . While thoridae) .Whichever method of identification is used by the practitioner to identify specimens must be mentioned in the report.The following proposed sections for an entomological case report have been adapted and extended from those proposed in the Standard Operating Protocol for medico-criminal case reports by the American Board of Forensic Entomology in 2009 :This should include a working postal or email address and contact telephone number. The practitioner’s title and affiliation should be included.3.Contact information of investigating officer or law practitioner :Again, a working postal or email address and contact telephone number, plus title and affiliation of contact person included.4.Instructions received:This section should include a brief note on when and how the practitioner was contacted and a precise description of what was being asked of them by the investigating officer or other person requesting evidentiary analysis.5.Case information (summary based on case file):The purpose of this section is not to restate the entirety of the case file; rather, a brief summary of the biographic details of the case  and details pertinent to the victim(s) and entomological evidence.6.Summary of insect evidence received, including at least a description of different developmental stages:Many practitioners relabel evidence once received, based on their own preferences or the labeling system of their laboratory. Both the original evidence details and the renamed details should be included here, to cover the bases for chain of custody.If vials containing evidence are split or repackaged for any reason, this should be indicated, with a reasonable explanation as to the reasoning behind repackaging . Vials that have been split into multiple sections must be relabeled, and new labels names indicated as well. This should follow chain of custody protocols as dictated by the regulating authority of the country.For preserved evidence, the time of collection and time of preservation should be included.If used, the preservation medium used by the practitioner should be indicated—often law enforcement officials do not have the necessary chemicals for preservation available at a collection scene and will use any suitable substance that is readily available . Evidence is then analyzed and replaced into vials with a more standard ethanol preservative (the concentration of which must be indicated).If live samples were provided, a detailed timeline of collection and transportation should be provided. This includes storage conditions , if oxygen supply was limited in a sealed container, as well as dietary medium provided during transport. If samples were further reared once reaching the practitioner, rearing details  should also be provided.This would also be an appropriate section to indicate any external factors that may have affected insect colonization and development on the remains .7.Environmental conditions obtained from weather stations:Since weather stations are not always conveniently located near crime scenes, it is advisable to use the most relevant climatic data available, from a certified meteorological organization, such as the national meteorological institution of your jurisdiction/country, and also indicate if data loggers placed at the scene after body discovery have been used to reconstruct scene data.The weather conditions at the time of insect collection should also be included if they were provided by the investigating officer.8.Identification of species and biological background:A brief background of the species identified should be presented, including geographic range and life cycle.Suitable references that have been used in the analysis should also be included here. These should include references to the identification keys, voucher specimens and molecular techniques used for identification and comparison;If a large number of specimens were provided, and only a subset analyzed, the criteria for subset selection should be mentioned.9.Estimation of insect age:This section, the bulk of the report, should be a brief summary of the estimation of the age of insect evidence based on temperature. This section should be broken down by species identified.10.Case summary (including date range of colonization if applicable):This section should highlight the most important findings and/or date range of colonization if applicable.There are a number of ways this could be presented; it may be helpful to separate date ranges by species, with a conclusive statement encompassing the chosen range.11.Criteria/caveats:There is a long list of criteria as stated above. It should not be necessary to include all of these, but definitely those most pertinent to the specific case. These can also be included wherever relevant throughout the report, rather than as a separate section.12.Declaration:This should be based on the requirements of the legal system into which the report is submitted, which can vary greatly, and include a statement indicating that analyses were performed based on currently available information and, should more information become available, the findings are subject to change.13.Signature:The report should be signed in accordance with the local requirements for documents of legal value.14.Accreditation statement (if available):A list of professional qualifications of the author can be included here, including professional qualifications and the number of cases worked. This section may be omitted where national legislature does not require it, or where pre-accredited lists exist which include such information.15.Reference list:Citations identified in the report should be provided. These citations support the approaches, interpretation, and conclusions made in the report (see discussion below).16.Supplementary documentation (if required):Chain of custody documents (courier receipts etc.) if available.Developmental data sets and calculations (upon request).Tabulated weather data (upon request).Locality:Where applicable, the datasets used should be based on insect populations as close to where the evidence was collected as possible. In cases where no local datasets are available, the practitioner should include a statement indicating that local data were not available. It must be noted, however, that developmental patterns by geographic separation may not always differ, and, in some cases, are comparable irrespective of location ,43.2.Species specificity:Where available, datasets pertaining to the actual species identified should be used. When this is not possible, it is preferable to exclude these species from analysis rather than use a dataset for a closely related species. However, the exclusion of such data is at the discretion of the practitioner, provided they maintain transparency regarding their findings, as sometimes it might be better to guide an investigation with a much more general conclusion based on data from a related species, suitably qualified with regard to accuracy, than to provide no conclusion. In such cases, the practitioner may refer to a generalized larval life cycle of the organisms concerned, or datasets for closely related species, to indicate a possible time of colonization estimate based on prevailing conditions. Irrespective of which sources a practitioner opts to utilize, these sources should be cited and the data should be accessible to any individual who is to read/analyze the submitted report.References included in the case report should reflect the locality of the entomological evidence as far as possible, as well as being relevant to the species identified. Key aspects to consider when compiling/utilizing references include:The goal of any entomological report is a reliable estimate of the TOC, which some interpret as a minPMI, of vertebrate remains by arthropods in cases where such events occurred after death. The report should be written and constructed in such a way that it is understood by individuals regardless of their level of scientific training. The report should be grounded in scientific principles and expertise, but not so saturated with scientific jargon that non-scientists struggle to understand or interpret the report. We acknowledge that an entomological report is not a scientifically peer-reviewed paper, but it should be prepared to the same high standards and, in order to meet legal standards , a significant element of scientific expertise is required. Quality assurance in entomological reports is of the highest importance, and fact-based evidence will be critical. However, it is acknowledged that every report will also contain opinion-based evidence, based on the knowledge and experience of the person compiling the report, and the judge presiding over the case will need to acknowledge that each case is unique and will need to be considered, in some aspects, independently of other case reports and studies .As indicated by the title of this communication, the points expressed above are recommended contents and points for consideration when compiling an entomological report for any legal purposes, including investigations of death, neglect, or stored product scenarios. As forensic practitioners, we understand that standards and legislation differ by country, and some sections may need to be revised to deviate slightly from those discussed, or the order of topics restructured to reflect the specific needs of the investigating officer or person requesting the report for its intended purpose . Without a global standard of legislature, the implementation of a standard entomological report may not be possible, but, at the very least, we hope this manuscript can provide a framework which entomological practitioners in any area can modify to develop a standardized report that is accepted by the respective jurisdiction in which the report is to be presented.


Dampened behavioral inhibition and overactive behavioral approach motivation systems(i.e. BIS/BAS) are associated with cannabis use disorder (CUD), although the underlyingneural mechanisms of these alterations have not yet been examined. The brain’s executivecontrol network (ECN) plays a role in decision-making and is associated with BIS/BAS. Inthis study, we tested the hypothesis that altered ECN resting-state functionalconnectivity (rsFC) underlies dysfunctional behavioral inhibition and approach motivationin cannabis users. To that end, we collected resting-state functional magnetic resonanceimaging scans in 86 cannabis using adults and 59 non-using adults to examine groupdifferences in the relationship between ECN rsFC and BIS/BAS. Our results showed that BISwas positively correlated with left ECN rsFC in cannabis users, while it was positivelycorrelated with right ECN rsFC in non-users. There was a trend-level moderation effect ofgroup on the association between BIS/BAS and ECN rsFC, showing a weaker association inBIS/BAS and ECN rsFC in cannabis users compared to non-users. An exploratory mediationanalysis found that the severity of CUD mediated the relationship between users’ BISscores and left ECN rsFC. These findings suggest that cannabis use may lead todysregulation in typical ECN functional organization related to BIS/BAS. Motivation mediates goal-directed behavior and is an important component of the addictionprocess. Specifically, an imbalance between increased drug-oriented motivation and dampenedbehavioral inhibition is considered to contribute toward the development and maintenance ofsubstance use disorders (SUDs). Empirical evidence for altered motivation in SUD has beenreported through behavioral assessments and cue-exposure paradigms —underlying motivated behavior . In thiset al., 2013). In substance abuse, there arecurrently three studies that examined differences in ECN and its relationship with BIS/BASalterations. These studies found greater resting-state functional connectivity (rsFC) in theleft ECN in stimulant . The ECN is a resting-state network (RSN) implicated in decision-makingprocesses related to goal-directed behaviors such as maintenance of sustained attention and response selection. The relationship betweenBIS/BAS and ECN appears to be lateralized. Studies have suggested that BIS is associatedwith the right ECN  recruitedfrom the Dallas metro area who provided informed consent to take part in a study aimed todetermine the neurobiological mechanisms of CUD . CannabiWe used the BIS/BAS scale to measuWe collected measures on lifetime and current CUD symptom using SCID. We also assesseddepression using the Beck Depression Inventory . Scans were collected while the participants were toldto close their eyes for 5 min and think about nothing in particular. High-resolutionstructural scans were collected using an MPRAGE sequence (TR/TE/Inversion Time (TI):8.2/3.70/1100 ms, flip angle: 12°, FOV: 256 × 256 mm, slab thickness: 160 mm alongleft-right direction, voxel size: 1 × 1 × 1 mm, total scan time: 3 min 57 s).MRI scans were collected using a 3T Philips whole body scanner equipped with Quasargradient subsystem  at the University ofTexas Southwestern Medical Center’s Advanced Imaging Research Center. Resting-statefunctional MRI (fMRI) scans were collected using a gradient echo, echo-planar sequencewith the intercomissural line (AC–PC) as a reference (Repetition Time (TR): 2.0 s, EchoTime (TE): 29 ms, flip angle: 75°, matrix size: 64 × 64, 39 slices, voxel size:3.44 × 3.44 × 3.5 mmDuring the second session, users were scanned following a 72 h abstinence from cannabisuse. Self-reported abstinence was verified via reduction in THC metabolites  (via GC/MS) following the 72 h abstinence relative to baseline. Participantswere also asked to abstain from alcohol for 24 h  and from caffeine and cigarettes for the 2 h before their scheduled scan. Onlyindividuals with confirmed abstinence were included in this study.We used t-tests to examine group differences on the three BAS subscale scores  and BIS scale scores between users andnon-users.The pre-statistical processing of rsFC data consisted of motion correction usingMCFLIRT, removal of timepoints corrupted by large motion using FSLMotionOutliers, brainextraction using BET and spatial smoothing using a Gaussian kernel of full-width athalf-maximum of 5 mm. To reduce very-low-frequency artifacts such as scanner drift, ahigh-pass filtering cut-off set at 100 s was applied. Registration to high-resolutionstructural and standard space images was carried out using FEAT (http://fsl.fmrib.ox.ac.uk/fsl).Given our interest in determining both within- and between-network connectivity, weselected an ICA approach (vs. seed-based connectivity). Noise components were identifiedand regressed from the single-subject ICA results using FMRIB's ICA-based X-noiseifier(FIX), before group ICA. FIX is an automated classification algorithm that attempts toidentify components as ‘good’ or ‘bad’ based on a set of training data obtained by firstmanually classifying a subset of participants’ components ,Version 3.15 part of FSL v. 6.0.0  to correlate BIS/BAS scoresand ECN rsFC. We modeled the main effects of BIS/BAS scores and group as well as theirinteraction on ECN rsFC. Seven GLM models tested the correlations between BIS and BASsubscale scores  and rsFC of the ECN inusers and non-users separately. These models were separated by group (two GLMs for usersand two for non-users) and by the scale being examined . The interaction effects of rsFC of the ECN and the BIS/BAS scoresbetween cannabis users and non-users were modeled using four additional GLMs. The firstGLM was tested using individual BIS scores as covariates, while the other three GLMswere tested using individual BAS subscale scores as covariates. Statistical thresholdingwas applied using FSL’s Randomise permutation-testing tool (5000 permutations). Clusterswere determined using threshold-free cluster enhancement and a FWE-corrected clustersignificance threshold of To evaluate a potential imbalance between the two motivation systems, we calculated theBIS:BAS ratio according to Schutter and colleagues  and non-users .Refer to The total number of individual components produced for each participant prior to noiseremoval ranged from 38 to 56 components. The number of components from each participantthat FIX classified and removed ranged from 5 to 24 components. The total varianceexplained by the independent components removed by FIX for each participant did notsignificantly differ between users  and BIS scoresand left ECN rsFC were greater in non-users than users.Groups moderated the association between BIS/BAS and ECN rsFC at trend-levelsignificance such that correlations between BAS reward subscale scores and left ECN rsFC(p = 0.025). The BIS:BAS ratio did notcorrelate with ECN rsFC in either group. There was no significant interaction effectbetween the BIS:BAS ratio and ECN rsFC in users and non-users.The BIS:BAS ratios in users were more negative, showing that users had a greaterimbalance toward BAS compared to non-users  and lifetime CUD symptom count. As an imbalance in BIS:BAS ratio may contribute to CUD initiation and maintenance, weexplored the relationship between the BIS:BAS ratio and CUD symptom count. The resultsshowed that the BIS:BAS ratio was positively correlated with current.We also found that there was a significant correlation between current CUD symptom countand left ECN rsFC   × (1.84) = 0.24. We tested the significance of this indirect effect usingbootstrapping procedures. Unstandardized indirect effects were computed for each of the1000 bootstrapped samples, and 95% confidence intervals (95% CIs) were computed. Thebootstrapped unstandardized indirect effect was significant ( < 0.05) . Because BIS:BAS may reflect an imbalance between RSNs rather than within ECN alone, wetested the notion that BIS:BAS may be a function of the interaction between the ECN andother networks, specifically, the salience network (SN) or the default mode network(DMN). For this post-hoc analysis, we used the same methods as described above toextract the SN and the DMN from ICA results . Becauseinteraction effects are typically small, it is possible that the absence of a significanteffect was due to statistical limitations related to the binary (vscontinuous) classification of cannabis use . Thehemispheric lateralization of BIS/BAS has been attributed to associated differences inemotional valiance/motivational direction  in substance use, which includes the relationship betweenmotivation systems and reward sensitivity as suggested by et al., 2011a; et al. (2011a) found that certain components of BAS, specificallyincreased fun-seeking and reward responsivity scores, can predict initiation of cannabis usein adolescents. Overall, the combined results of the van Leeuwen et al.’s(2011a) study in adolescents and our current study of residual cannabis use effects inregularly using adults suggest that altered components of behavioral approach contribute tocannabis use initiation and maintenance.Consistent with previous findings, we found higher BAS fun-seeking subscale scores and amore negative BIS:BAS ratio in users compared to non-users . This suggests the possibility that dysregulation in neural networksmay be remediated with the resolution of CUD. Taken together, these findings provideevidence for individual differences in the neuropsychopathology of addiction of Determining the underlying neural mechanisms of the BIS/BAS and their relationship tocannabis use provides important information for the advancement of treatment and preventionstrategies. Specifically, differential relationships between BIS and BAS components with ECNnetwork connectivity likely alter cannabis users’ evaluation of choices when making adecision. This altered processing of choices, as evidenced by increased BAS fun-seekingscores and an imbalance toward BAS in the BIS:BAS ratio, likely leads to risky decisionsthat contribute to the initiation and maintenance of cannabis use. Thus, emphasizingeffective decision-making and challenging cannabis users’ propensity to value rewardingoutcomes while downplaying potential consequences of their choices may help decrease relapserates and improve poor treatment outcomes in CUD treatment .Interpretation of these findings should take into consideration that our primary finding ofinteraction effects was weak and only approached trend-level significance. While interactioneffects often suffer from low statistical power, these findings demonstrate largecorrelations between BIS/BAS and rsFC in cannabis users and non-users that future studiesshould consider.The implications of the current study’s results are also limited by the duration of theresting-state scan (i.e. 5 min). While there is currently no standard optimal scan duration,arguments have been made for longer resting-state fMRI scans to increase the reliability andstability of results (To conclude, we found implications of disrupted ECN organization that underlie BIS incannabis users, which is partially mediated by the severity of CUD. These findings suggestthat cannabis use may lead to dysregulation in typical ECN functional organization relatedto BIS/BAS. Dysregulation of BIS may underlie attenuated motivation to avoid harm thatcontributes to risky decision-making in cannabis users.nsab054_SuppClick here for additional data file.


Proper collection and analysis of physical evidence including insects, bloodstains, or any other material can be of probative value in a court of law. This is the first casework where hairs were involved as insect-related evidence. Hairs constitute important categories of trace evidence as they can provide useful information for an association between a suspect and a crime scene or a suspect and a victim. Two “cold cases” occurred in two different European countries in which the trace evidence relating to insects was the last piece of a complex puzzle useful for the conviction of the perpetrator.Insect-related evidence must be considered of probative value just as bloodstains, fingerprints, fibers, or any other materials. Such evidence if properly collected and analyzed can also provide useful details in the reopening of old unsolved murders, also called “cold cases”. This paper presents the case of two murders that occurred in two different European countries and remained unsolved for years. The remains of a girl found in Italy 17 years after her disappearance helped to solve a murder that occurred in Britain 8 years prior. The cases were unexpectedly linked together because of the similarities in the ritualistic placing of strands of hair and connections with the suspect. The trace evidence relating to insects and hairs played a relevant role in the conviction of the perpetrator. In Italy, the defense raised the doubt that the strands of hair found nearby the skeletal remains could be the result of insect feeding activity and not the result of a cut by sharp objects. Therefore, it was fundamental to distinguish between sharp force lesions and insect feeding activity on hair. This unusual application of insect-related evidence clearly emphasizes the importance of an appropriate professional collection and analysis of any physical evidence that could be of robust probative value. The major goal of medicocriminal entomology is the determination of time, cause, and manner of an investigated death . The mosSeveral useful elements can be inferred from the study of insects found on the cadaver or nearby. The correct analysis and interpretation of insect evidence can be crucial in any death investigation, especially when dealing with badly decomposed or skeletonized human remains. Insect-related evidence can provide valuable information to answer questions concerning the use of drugs, child and elderly neglect, sexual abuse, cadaver transfer and concealment of the remains following death, victim identification, determination of specific sites of antemortem trauma, and postmortem artefacts on a body and at the death scene ,7. The fTherefore, insect-related evidence must be considered of probative value just as bloodstains, fingerprints, hairs, fibers, or any other biological materials. In the recent past, several papers have highlighted the crucial role of correct procedures in sampling and storing entomological evidence ,9,10. IfThis paper presents the case of two murders that occurred in two different European countries and remained unsolved for years. The murders were unexpectedly linked together because of the similarities in the ritualistic placing of strands of hair and connections with the suspect. Hair evidence and its postmortem infestation by insects played a relevant role in the conviction of the perpetrator. The remains of a girl found in Italy 17 years after her disappearance helped to solve a murder that occurred in Britain 8 years prior.Diptera puparia (mostly parasitized) and cast pupal skin of clothes moths (Lepidoptera) were present on the body and nearby the corner of the church’s loft where the victim was dragged and concealed. Among the Diptera species, Sarcophagids, Phoridae, Fanniidae, Muscids of Muscina stabulans, and Calliphorids of Calliphora vicina, Lucilia sericata, and Chrysomya albiceps, on which the clothes moths fed, were found  were found on the skeletal remains. Large amounts of re found . Among ted hands .The murder case showed some coincidences with a similar case that occurred in England 8 years prior. A 48 year old seamstress was found dead in her apartment on 12 November 2002. The woman was beaten with a hammer-type object before her throat was cut and body mutilated. She was also stabbed several times and strands of hair were placed in both of her hands. The lock of hair in the victim’s left hand was cut from her own head, but that in her right hand was not hers. The main suspect in this murder was the victim’s neighbor. He was a 39 year old Italian male who arrived in England several years before from a small town in southern Italy, where the teenage girl went missing. Although the neighbor initially became the main suspect, the British police was unable to collect sufficient evidence for prosecution. After the discovery of the Italian girl in 2010, the cases were linked together because of the similarities in the ritualistic placing of strands of hair and connections with the suspect. The manner in which the English woman was murdered was considered a trademark of the suspect, and the killing was linked to the murder of the adolescent girl in Italy. Two months after the discovery of the Italian girl in 2010, the suspect was arrested in England and charged with the murder of the British woman. In June 2011, he was found guilty by the English jury and sentenced to spend the rest of his life in prison. On October 2014, he was also condemned by the Italian Supreme Court to 30 years in prison for the murder of the 17 year old teenage girl.At the trial, the perpetrator consistently denied any involvement in both cases. However, under cross-examination he admitted to having a hair fetish and cutting the hair of girls occasionally met on the street. He liked to touch and smell the hair of girls without planning cutting episodes. According to such admission, the two murders were referred as hair fetish murders. Hair fetishism or trichophilia is a paraphilia, which is a sexual perversion, a condition characterized by abnormal sexual desires. In the case of hair fetishism, seeing or touching hair is particularly erotic and sexually arousing for a person . During Tineola bisselliella Lepidoptera, Tineidae) and carpet beetles  [In Italy, the defense raised the doubt that the strands of hair found nearby the skeletal remains were not cut by sharp objects but could be the result of insect feeding activity on hair. Therefore, it was fundamental to distinguish between sharp force lesions and insect feeding activity on hair. In order to study if the features in hair lesions were caused by traumatic/sharp forces or by insects, hair samples were subjected to blunt and sharp force trauma and used as pabulum for common clothes moth (estidae) . These sestidae) ,15, feedestidae) . Artefacestidae) .The hair samples examined by stereomicroscopy and scanning electron microscopy (SEM) showed clear differences in hair lesions depending on the type of trauma. They can be summarized as follows: (1) irregular edges without striations and concavities, but with hair elements on different levels in hair locks manually broken; (2) regular edges with parallel striations (similar to marks from sharp weapons observed on bone and cartilage) and hair elements on the same plane in hairs cut by a knife, with the same features but of oval shape due to the compression of the two edges of scissors in hairs cut by scissors; (3) irregular edges with concave shape lesions and cocoons in hair locks used as pabulum for insects .The strands of hair found close to the hands of the victim showed regular edges of the hair lesions with parallel striations of oval shape consistent with hairs cut by scissors. These findings and the results of the experimental study were considered of probative value. The hair lesions distributed on the same plane were clearly cut and not the result of gnawing activity easily distinguishable from breaking and tearing. In the Italian case, the hypothesis of insect feeding on hair was ruled out.Hair evidence is one of the most common pieces of physical evidence applied in criminal investigations . The forDiptera larvae can also produce relevant modifications of superficial injuries on the human body. Stab wounds and gunshot injuries can be easily enlarged, distorted, or made unrecognizable by the feeding larval activity at the injury site [At a death scene, fly and larval activity can produce several different types of artefacts: from fly specks due to regurgitation and defecation to floor and wall stripes due to post-feeding larval dispersal . Other mury site . Larvae ury site ,24.Diptera puparia.Artefacts made by insects that arrive late on the body are also reported. Dominant taxa in the late stages of decomposition are commonly species of Coleoptera and Lepidoptera such as the clothes moths (Tineidae), very common in mummies and skeletonized bodies ,15. Thesn-acetylglucosamine that is similar to keratin in human hair. Keratin and keratin-associated proteins are the major structural components of human hair fiber. Human hairs are proteinaceous shafts with circular or elliptical cross-sections with three morphologically distinct regions in each hair  [Puparia consist largely of chitin, a long, complex polysaccharide polymer composed of cuticle) . They cacuticle) . The strDiptera puparia may represent useful evidence for reconstructing postmortem events in both forensic and archaeo-funerary contexts [The structure and mechanical properties of puparia and human hair explain why sclerotized puparia and hairs do not degrade much, which allow samples to survive for thousands of years ,26. Fly contexts . Howevercontexts .The taphonomic degradation process for teeth and bones is well studied, but the same cannot be said for human hair as very little is known about how environmental conditions may alter hair morphology . A recenFungi and bacteria can break down hair; however, insects such as clothes moths and carpet beetles can also easily destroy such evidence as they feed on dried food sources such as natural fibers ,35,36. MThe mutually beneficial relationship between research and casework was largely discussed by Hall . The unuThe take-home message is to call the attention of forensic entomologists to hair examination in skeletonized or mummified bodies or in an advanced stage of decay. Forensic experts should cover every corner of the crime scene and treat each and every piece of evidence as vital. Investigative research has contributed to advancing knowledge of the basic biological and ecological processes of human and animal decomposition, increasing the chances for the admissibility of entomological evidence ,40. Beca


While epidemiological and economic evidence has the potential to provide answers to questions, guide complex programmes and inform resource allocation decisions, how this evidence is used by global health organisations who commission it and what organisational actions are generated from the evidence remains unclear. This study applies analytical tools from organisational science to understand how evidence produced by infectious disease epidemiologists and health economists is used by global health organisations. A conceptual framework that embraces evidence use typologies and relates findings to the organisational process of action generation informs and structures the research. Between March and September 2020, we conducted in-depth interviews with mathematical modellers (evidence producers) and employees at global health organisations, who are involved in decision-making processes (evidence consumers). We found that commissioned epidemiological and economic evidence is used to track progress and provides a measure of success, both in terms of health outcomes and the organisations’ mission. Global health organisations predominantly use this evidence to demonstrate accountability and solicit funding from external partners. We find common understanding and awareness across consumers and producers about the purposes and uses of these commissioned pieces of work and how they are distinct from more academic explorative research outputs. Conceptual evidence use best describes this process. Evidence is slowly integrated into organisational processes and is one of many influences on global health organisations’ actions. Relationships developed over time and trust guide the process, which may lead to quite a concentrated cluster of those producing and commissioning models. These findings raise several insights relevant to the literature of research utilisation in organisations and evidence-based management. The study extends our understanding of how evidence is used and which organisational actions are generated as a result of commissioning epidemiological and economic evidence. Despite numerous initiatives to enhance knowledge utilisation, the understanding of how burden of disease and vaccine impact estimates are used by global health organisations that commission research evidence production is limited.Our study draws on an organisation science framework to examine the role of burden of disease and vaccine impact estimates for global health organisations.We found that burden of disease and vaccine impact estimates are not directly translated into organisational actions but are used by global health organisations to demonstrate accountability, to solicit funding and to get the buy-in from external partners.We found that evidence consumers can perceive evidence as ‘negative’, if their entrenched knowledge, built up over time, is challenged, or if the evidence does not meet their expectations, thus impeding its use.Interactions between evidence producers and consumers are vital so that evidence is produced in correspondence to questions of evidence consumers.Commissioned models, global in their scope, appear to serve a specific purpose, distinct from other academic modelling efforts.Their value lies in their ability to track progress and thus advocate for resources.Is there a missed opportunity given their disconnect from national-level resource allocation decisions?Cocreating a research agenda may enhance evidence consumers’ willingness to embrace model limitations and caveats thus allowing for more innovative methods to be employed in the evidence production process.In addition to domestic efforts, global health organisations (GHOs), such as the Bill & Melinda Gates Foundation and associated partnerships, such as the Global Alliance for Vaccines and Immunization, play a prominent role in low and middle-income country (LMIC) immunisation programmes.6In the effort to act on the impact of long-standing, emerging and re-emerging infectious diseases, GHOs work closely together with researchers by commissioning research projects that have the potential to solve complex problems.12–14Despite numerous initiatives to enhance knowledge utilisation, the understanding of how BOD & VIE are used by GHOs is limited. Research utilisation studies have predominantly been conducted in other organisational contexts. Therefore, the objective of this study was to understand how BOD & VIE are used by the GHOs that commission the research and what actions are generated following the commissioning of evidence production.action generation. Evidence use in the process of action generation is ascribed to three overarching categories of evidence use: instrumental, conceptual and symbolic.Research for this paper was informed by a conceptual framework, which addresses possible types of evidence use throughout different organisational processes.10.1136/bmjgh-2021-006827.supp1Supplementary dataet al to study research utilisation.28We conducted in-depth, semistructured interviews to explore how global BOD & VIE are used by GHOs as recommended by Hanney evidence producers and evidence consumers. For the purpose of this study, mathematical modellers commissioned to produce global BOD & VIE take up the role of evidence producers. Producers include individuals who work as epidemiologists or health economists at a research institution and who have extensive experience in the mathematical modelling of vaccine-preventable diseases. Moreover, they produce and disseminate BOD & VIE as academic outputs with the intent to inform decision-makers. Producers were initially identified as individuals, who are specialised in the mathematical modelling of a vaccine-preventable disease and were commissioned to produce the specific type of research evidence, global BOD & VIE by GHOs. Evidence consumers are employees at GHOs that commission research to, among other things, inform global resource allocation decisions and strengthen global immunisation systems through their organisational strategy. Consumers were initially identified by researching profiles of individuals employed at GHOs that grant funding to evidence producers and provide DAH to countries to support global vaccination initiatives. Evidence consumers do not have to be the final decision-makers but can sit along the pathway from receiving evidence to disseminating it to higher level decision-makers within the organisation . This is important to note as previous studies have found that decisions are rarely made by a single individual31Beyer and Trice identify two main stakeholder groups in research utilisation: consumers may have taken the role of producers in previous occupations or may even be evidence producers as part of their current position within their organisation. Therefore, we assign the informant to the organisation where they are employed at the time of the interview. We recognise that BOD & VIE may also be produced within the organisations at which the evidence consumers are employed. For this reason, we specifically asked informants about the use of global BOD & VIE that were formally commissioned to external constituencies.We acknowledge that the line between evidence producers and consumers is blurred.Data were collected from purposively sampled individuals between March and September 2020 by PC. Snowball sampling was used to expand the study population to those who had not been identified previously but matched the outlined study eligibility criteria. Data saturation was achieved when ideas and/or opinions were repeated in different interviews. All interviews were conducted via the telecommuting software Zoom. Informed consent was obtained for every participant. A prewritten interview guide with open-ended questions was used . Additio3310.1136/bmjgh-2021-006827.supp2Supplementary data10.1136/bmjgh-2021-006827.supp3Supplementary dataIn total, we approached 21 potential participants, 2 individuals refused to participate and 6 individuals did not respond. Interviewees included seven evidence producers (epidemiologists (n=6), a health economist (n=1)) and six evidence consumers (senior programme officers (n=4), team lead of the department of immunisation (n=1), medical epidemiologist in the department of immunisation (n=1)). All evidence producers held a position as postdoctoral fellow (n=3), assistant professor (n=2) or professor (n=2). Evidence consumers held a PhD (n=4), MSc (n=1), MPH (n=1) and/or MD (n=2). All interviewees were based in Europe (n=5) or North America (n=7), except for one evidence producer based in Asia.The data were analysed using the framework method developed by Ritchie and Lewis,Our results focus on how global BOD & VIE are used and what actions are generated by GHOs as a result of receiving this evidence, with respect to the research utilisation spectrum and associated explanatory models , and draThe design and conduct of the study, the development of the research question and outcome measures did not involve patients.Instrumental evidence use describes the systematic production and use of evidence in a linear process, implying that BOD & VIE would directly influence a decision or act as a solution to a specific problem. In line with this interpretation, there was general agreement and criticism among evidence producers and consumers that the production of BOD & VIE is dictated by evidence consumers, who set out the research agenda explicitly by providing funding for specific types of evidence. Yet, no specific decisions made by GHOs could be traced to a specific piece of research.For this model to apply, production of research evidence considered for use by evidence consumers should be driven by academic curiosity. Evidence producers and consumers agreed that this is rarely the case; however, opportunities exist for more of the processes along the evidence use route to be more knowledge driven.An evidence producer highlighted that evidence producers should lead the discussion on ‘what should be done’ that would be of value to evidence consumers. Thereby, the research agenda should be agreed on for each pathogen and for mathematical models of the same pathogen  (P1). The interviewee described the research agenda to be determined by evidence consumers:We aren’t answering any questions about really what is actually happening at the policy level whether it is country-level policy and decision-making or global […] level decision-making. […], we are handed the demographics, we are handed the coverage assumptions and it is just running it through a population [pathogen] model, by age and time, to say what the impact of those assumptions would be. We are not really doing anything in terms of the research agenda. (P1)Evidence consumers and producers argued against the value of following the knowledge-driven route to evidence use. Informants stressed that changes in long-standing mathematical models can be a barrier to evidence use, as one evidence producer highlighted:… for the most part, we are always a little cautious about dramatic changes in models because we’re really trying to translate observed changes in coverage, which is what [a GHO] has been investing in and understanding what that means for deaths averted [rather than] new modelling assumption. (C1)Furthermore, evidence producers  referred to the delicate balancing act of responding to specific commissions for prescribed global burden models, while also still trying to fund models driven by more personal academic interests linked to knowledge gaps and methodological advances:It’s sort of a little like a chicken and egg thing, I think. Like, you want to have those discussions, but […] I think, people don’t feel that they should give you the time or why would they give you the time if you haven’t done some work already? (P2)There was a general agreement that a linear evidence production and consumption process, initiated by evidence producers, is rare and unrealistic given its reluctance towards innovation and changes in evidence.Interviewees addressed some principles of instrumental evidence use following the problem-solving model indirectly through the process of commissioning evidence producers and setting out deliverables through contractual agreements.Both evidence producers and consumers stressed that evidence production is led by evidence consumers as they are commissioning the evidence production. Thereby, the evidence consumer is viewed as a major influence on evidence production and determines its direction and organisation (C4). They predetermine research questions and become ‘technical agencies’ determining the research agenda, as one interviewee stated:When you, as an academic institute get funding, you will not argue with your donors, which are funding you. So, you follow the donor, you follow the money. […] [The funding organizations] are not only funding, they are doing more and more technical assistance, they are very much involved in the model set up, in everything from contracting to implementing. (C4)An evidence producer also raised concern about the fact that the research agenda and problem definition is led and decided on by evidence consumers. While progress, goals and activities are discussed, grant deliverables that define the research agenda are set ex ante (P7). Evidence producers and consumers stated that this ignores the expertise of the evidence producer, who is arguably more aware of what requires further research . However, an evidence producer highlighted that commissioned research should be the result of discussions for the evidence to be ‘usable’ to decision-makers:I’d say that the questions need to be applicable, usable, and so [the decision-makers] very much should be in the discussion of setting those questions. (P6)Interative Model).It is evident that the interviewee sees value in more interaction between actors, also reflected in the interactive model (section Questions posed by decision-makers when commissioning research may not necessarily be the ‘right’ questions or lead to decisions that are ‘right’ (P2). An evidence producer raised concerns that aggregating the impact of all mathematical models and projecting results to a global scale limits sufficient attention on specific national and subnational questions. For example, assumptions that all children who have received a first vaccine dose are also administered the second vaccine dose if required can lead to misleading outcomes (P1).In this next subsection, we explore the extent evidence permeates actions in more indirect ways leading to incremental changes in knowledge, understanding and/or attitude of evidence consumers as a result of using BOD & VIE.According to informants, evidence influences the organisational agenda incrementally over time. Which vaccines drive the most impact is ingrained in people’s knowledge as estimates have been seen many times (C2):Our management isn’t using the numbers in a one-to-one way to make trade-offs. But it’s more that this is really foundational information for us to understand what the most important areas for us are to invest in. And then that drives more on an underlying fundamental basis, what we invest in immunizations. (C2)Another evidence consumer highlighted that the evidence is not used by decision-makers at a high level to understand details of the impact of pathogen-specific interventions that are modelled mathematically  (C5).Further, investment decisions made by an organisation’s management affect the work of all other departments within the organisation (C2):So [BOD & VIE are] not the only thing that we would factor in, but it would be something that helps us to prioritize which countries we will most focus on investing in. And then that trickles down to all the rest of our work. (C2)Therefore, research evidence shows to be ‘creeping’ into decisions, which is consistent with principles of the enlightenment model to evidence use. The applicability of the enlightenment model is further discussed under specific subthemes.Interactive Model). If the evidence does not support the evidence consumer’s belief, and questions How well has the model done at predicting things that we know have happened in the past? Why are model estimates not meeting the consumers’ expectations? Can estimates be trusted? (P4)What explains changes in the mathematical model which affect the estimated impact? Do we believe that these are good changes or are they going to end up going the other direction the next year when the modellers update their assumptions again? (C1)Is a change in BOD & VIE the result of something that happened in the world? Did the coverage decrease? Did the production not happen? Did something in the model change? Did the understanding of the epidemiology of a pathogen evolve? (C2)What drives differences in impact estimates from different models? Are the multiple models valid for the same pathogen? Is there an error in one of the models? (C2)What can models do and cannot do? What improvements may be needed? With the aim of eliminating specific diseases, how does the mathematical model need to be aligned or changed? (P1)What is the population-level impact that goes beyond direct protection (herd immunity effect) in lower income settings where data are limited? (P5)How can estimates be additive in terms of not just using them in a vacuum, but using them to better understand and validate admin data estimates that come out? (C5)How do you interpret the relative contribution of different source of vaccination to the overall burden? That is, routine immunisation programmes (multiple doses), pulse national campaigns or national or subnational campaigns, outbreak response. (P3)What are the assumptions around the treatment for a disease? (C1)As of interviewees’ accounts, the dissemination of BOD & VIE is often formally set out through reporting channels. This challenges the applicability of the enlightenment model, which defines the route of evidence permeation to be unguided and indirect. Tools to disseminate evidence suggest a guided evidence use process; however, the understanding of evidence cannot always be facilitated through these means as the argument-generating questions suggest.Social interaction allows evidence to be produced with reference to what evidence consumers need to know in an iterative process (C4). Therefore, evidence consumers should be included in the early stages of the evidence development, including the set-up of the model structure and defining the outcomes that are required . Further, social interactions are required to answer the questions .Moreover, interactions through long-standing relationships reduce disruptiveness when the evidence changes over time, especially if conclusions are different from previous ones, leading to a shift in resource allocations . Changes in mathematical models and evidence supplied to consumers were viewed as a major point for discussion in interactions between evidence producers and consumers. Foundational knowledge, which has entrenched within evidence consumers over time, is being challenged, if new evidence does not meet its consumers’ expectations (P4). A lack of relationships may lead to challenges when trying to get the buy-in from stakeholders to use the evidence .Overall, there was a consensus among evidence producers and consumers that the interactive model should define the route to evidence use. However, this model cannot necessarily be used to explain the current evidence use at stakeholders’ organisations. Interactions, especially at an early stage of evidence production, are required specifically for ensuring that evidence and its limitations and caveats are understood to promote its use and avoid evidence consumers ignoring it.Under the symbolic evidence use category, which stands in stark contrast with instrumental evidence use, evidence is used in a strategic manner for decisions that have already been taken. The symbolic use identified in this study aligns with the political explanatory model, that is, evidence is used to support the evidence user’s standpoint. No respondents spoke of the tactical model where solely the fact that research is being conducted is used in evidence users’ actions.An evidence consumer interviewee refers to ‘meta-questions’, which should be addressed by evidence producers (C5):But [evidence producers are] answering kind of a more existential question rather than a specific programmatic question. (C5)Probing revealed that evidence from mathematical models is mainly used for strategic thinking, planning purposes (C3), accountability and advocacy purposes when engaging with external funding partners of evidence consumers . BOD & VIE are used to solicit funding for further rounds of funding from donor partners (C1):The impact numbers are probably the most important numbers that we use for replenishment efforts and for reporting to donors, so for high-level kind of accountability. (C1)Sometimes, evidence is used for framing the setting or as contextual information for anyone trying to make the case for why the organisation should invest in a particular project over another one (C2). Evidence on vaccine impact comes into play when someone needs supporting evidence for his/her argument (C2) or to track the organisations’ progress (C5).An evidence producer stated that despite estimates from multiple models for the same pathogen being hugely different, the main conclusions remain (P4). Details on BOD & VIE are of less interest to evidence consumers (C4). Rather, evidence consumers are interested in the direction of impact to support his/her argument (C4).Overall, the political model describes evidence use once the evidence is engrained in the decision-makers’ understanding and the organisation’s agenda. Evidence consumers agree that research evidence is often used to inform and communicate targets to donors and to support an argument when wanting to receive more funding. Evidence producers did not provide any information alluding to the applicability of the political model.This paper set out to examine how one type of commissioned research evidence  is used by GHOs that aim to strengthen global immunisation systems. The findings highlight that BOD & VIE are not directly translated into GHOs’ actions, that is, systematically translated into vaccine resource allocation decisions, but are used to demonstrate accountability and solicit funding from external partners. While GHOs’ actions are partially influenced by BOD & VIE, the evidence is mainly used anecdotally. With regard to the conceptual framework used to analyse the results, the conceptual model and the political model best describe how evidence is used by GHOs.Previous studies have furthered our understanding of evidence use by individuals, national governments and organisations on a variety of public health policies and decisions, such as maternal and child healthGHOs operate in a highly competitive environment.BOD & VIE also come into play when someone requires supporting evidence for their argument within the organisation. GHOs are ‘political’ organisations, in which several potentially conflicting interests and stakeholder groups exist.Research evidence use by GHOs happens over a prolonged time in which many people within the organisation learn about the evidence. Over time, evidence on disease burden and vaccine impact becomes ingrained in people’s knowledge. From organisational theory, we learn that organisational norms and objectives are entrenched in employees’ minds.et al advocate for platforms for exchange and the institutionalisation of a multistakeholder approach.50This study showed that, unsurprisingly, open interactions between evidence consumers and producers are vital to facilitate understanding of the evidence and its caveats and limitations.Consistent with findings of previous studies, our study showed that trusted relationships can lead to trust in evidence and the acceptance and adoption of new evidence, which may otherwise be regarded as controversial or ‘negative’ evidence.While the benefits of interactions among evidence producers and consumers became obvious through this and other research, this process can also jeopardise the objectivity of the scientific community. The objectivity of the scientific community may be questioned if the political interests of research commissioners inhibit knowledge production. While this was not voiced by evidence consumers or producers interviewed for the purpose of this study, evidence-informed decision-making interventions that aim to enhance the dialogue between stakeholders need to reflect on the role of power and politics in the process of knowledge production.55Mathematical models of infectious diseases have increasingly gained attractiveness among global health actors as they complement other epidemiological studies (eg, clinical trials58Despite the growing number of organisations and actors in the global health system, it is strongly influenced by only a few entities that are headquartered in high-income countries,This study has its limitations. First, study participants’ responses may have been subject to social desirability. Both parties may have voiced their idealistic evidence use rather than the actual evidence use. Second, interviews were meant to have been conducted in person. Sometimes, it was difficult to grasp participants’ voices, opinions and non-verbal communication via video calls. However, this method of collecting primary data is considered a viable alternative to conducting interviews face to face.61 62In conclusion, we found GHOs use BOD & VIE to demonstrate impact and accountability at the global level, often to solicit funding to support global immunisation efforts. GHOs that commission research evidence production and consider using research evidence should be engaged continuously throughout the research production process to maximise the value of BOD & VIE. Similarly, evidence producers should be engaged when GHOs use their research products. BOD & VIE are used to convince others of organisational legitimacy and may have had a direct influence on national, subnational and local vaccine resource allocation decisions. Yet, global BOD & VIE have been underused and only impacted GHOs’ actions indirectly. Arguably, global BOD & VIE have greater potential and can lead to more informed organisational actions, such as guiding vaccine resource allocation decisions across countries, not only to track progress and measure organisational success.