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Language bias in randomised controlled trials published in English and German.

BACKGROUND: Some randomised controlled trials (RCTs) done in German-speaking Europe are published in international English-language journals and others in national German-language journals. We assessed whether authors are more likely to report trials with statistically significant results in English than in German. METHODS: We studied pairs of RCT reports, matched for first author and time of publication, with one report published in German and the other in English. Pairs were identified from reports round in a manual search of five leading German-language journals and from reports published by the same authors in English found on Medline. Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors' identities, affiliations, and other characteristics of trial reports. Main study endpoints were selected by two investigators who were unaware of trial results. Our main outcome was the number of pairs of studies in which the levels of significance (shown by p values) were discordant. FINDINGS: 62 eligible pairs of reports were identified but 19 (31%) were excluded because they were duplicate publications. A further three pairs (5%) were excluded because no p values were given. The remaining 40 pairs were analysed. Design characteristics and quality features were similar for reports in both languages. Only 35% of German-language articles, compared with 62% of English-language articles, reported significant (p < 0.05) differences in the main endpoint between study and control groups (p = 0.002 by McNemar's test). Logistic regression showed that the only characteristic that predicted publication in an English-language journal was a significant result. The odds ratio for publication of trials with significant results in English was 3.75 (95% CI 1.25-11.3). INTERPRETATION: Authors were more likely to publish RCTs in an English-language journal if the results were statistically significant. English language bias may, therefore, be introduced in reviews and meta-analyses if they include only trials reported in English. The effort of the Cochrane Collaboration to identify as many controlled trials as possible, through the manual search of many medical journals published in different languages will help to reduce such bias.

Bias↗

The interface between publicly funded and industry-funded research in pediatric psychopharmacology: opportunities for integration and collaboration.

Pediatric psychopharmacology research is undergoing a major expansion consequent to increasing use of psychotropic medications in children and recent legislative incentives to industry. In this rapidly changing context, the interface between publicly and privately funded research needs to be reconsidered to integrate activities and avoid unnecessary duplication of efforts. Once, by default, the almost exclusive domain of public research, child research is now increasingly funded by industry. There are, however, important issues unlikely to be addressed through private funding for which public support is needed, such as direct comparisons between active medications, between pharmacological and psychosocial interventions, or between combined and single treatment modalities; development of effective treatment strategies for patients unresponsive to first-line treatments; development of better research methods to assess efficacy and safety; identification of moderators and mechanisms of treatment response; and impact of treatment on illness course and prognosis. Industry-sponsored research is limited by the restricted access to proprietary databases, which impedes independent analyses and meta-analyses. Translation of basic neuroscience discoveries into treatment applications for children with mental illness is a critical area of inquiry that can benefit from integration of efforts and collaborations among academia, government, and industry.

Adolescent↗

International School Health Network: an informal network for advocacy and knowledge exchange.

In Canada, researchers, policy-makers and non-governmental organisations have re-conceptualized the school setting as being an ecological entity, linked to parallel ecologies of the homes and the community it serves. The school, public health and other systems that seek to deliver programs in that setting are open, loosely coupled and bureaucratic. This reconceived view of the school as a setting for health promotion leads to an emphasis on building organizational, system, professional and community capacity. One of the most effective ways of building such capacities when resources are scarce is to invest in a variety of formal and informal networks that can sustain themselves with little or no external resources. A number of recognised researchers from the health and education sectors have emphasized this systems-based approach and the need to build supportive, small-scale networks or learning communities. In recent health promotion research, networking at various levels, across sectors and within communities is viewed as a key strategy within new, more effective health promotion strategies. In education, the notion of networking for educational change has been described as "learning communities" for continuous school improvement. The authors suggest that this strategy of networking be used at the international level to address several global challenges: There is no single, convenient way to obtain basic information about the status and nature of national and state/provincial school health programs around the world. There is no global research agenda in school health promotion, despite the obvious value of sharing such research and knowledge. There is no global mechanism to facilitate the development of common or shared tools for surveillance of child/youth health and monitoring of school health policies and programs, despite the excellent work being done in individual countries and by the European Network of Health Promoting Schools. There is no international mechanism with a focus on school health that brings together the following stakeholders: educational organisations with public health organisations; researchers with government officials and practitioners; those who work in Spanish, English, French and other languages; issue-specific networks with health generalists. An invitation is given to government officials, researchers and national school health associations to join an informal International School Health Network (ISHN) (soon available at: www.internationalschoolhealt.org). Discussions about the formation of the ISHN have been held with a number of participants at several international meetings and have culminated in a fledgling network that will focus on electronic and web-based exchanges of information, developing a global school health research agenda, exchanging effective materials and tools, informing policy-makers about effective practices, policies and programs. This network would build on and not duplicate the work of existing networks and include participation from WHO, OECD, UNESCO, the IUHPE and the World Bank. The next large meeting of the ISHN will occur at the IUHPE 2007 Conference in Vancouver, Canada (www.iuhpe conference.org). Before then the ISHN will organise several on-line projects and teleconferences. For more information, contact dmccall@jcsh-cces.ca.

Communication↗

Interventions for replacing missing teeth: surgical techniques for placing dental implants.

BACKGROUND: Many variations in the surgical technique for the placement of dental implants have been developed since the introduction of implant surgery into clinical practice. These include variations in the timing of implant placement in relation to the tooth removal, and variations in the way the recipient bone site is prepared, amongst others. OBJECTIVES: To test the null hypothesis of no difference in the success, function, morbidity, patient satisfaction and cost-effectiveness of different surgical techniques for placing dental implants, against the alternative hypothesis of a difference. SEARCH STRATEGY: The Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE were searched. In addition, the bibliographies of review articles were checked for studies outside the handsearched journals and personal references were searched. 55 implant companies were also contacted. SELECTION CRITERIA: Randomised controlled clinical trials (RCTs) of implant surgical techniques. DATA COLLECTION AND ANALYSIS: Authors were contacted for details of randomisation and data and quality assessment was carried out (ME, PC). Data were independently extracted, in duplicate, by two reviewers (HW, PC). The Cochrane Oral Health Group's statistical guidelines were followed. MAIN RESULTS: Four RCTs (six publications) were suitable for inclusion in this review of the nine RCTs (11 publications) identified. Two different aspects of implant surgical technique were reported in these RCTs. These were, two versus four implants to support a mandibular overdenture and crestal versus vestibular incision for implant placement. At the patient level there were no statistically significant differences for any of these alternative techniques with respect to implant failures, marginal bone levels, morbidity or patient satisfaction. REVIEWER'S CONCLUSIONS: This review included studies evaluating the surgical techniques of two versus four implants to support a mandibular overdenture and crestal versus vestibular incision for implant placement. Based on the available results of RCTs, there is no strong evidence supporting superior success with one or other of the alternative techniques for either of these two aspects of surgical technique. These conclusions are based on a few RCTs for each aspect of surgical technique and some with relatively short follow-up periods and few patients.

Dental Implantation, Endosseous↗

A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury.

From the beginning, the reporting of the results of National Acute Spinal Cord Injury Studies (NASCIS) II and III has been incomplete, leaving clinicians in the spinal cord injury (SCI) community to use or avoid using methylprednisolone in acute SCI on the basis of faith rather than a publicly developed scientific consensus. NASCIS II was initially reported by National Institutes of Health announcements, National Institutes of Health facsimiles to emergency room physicians, and the news media. The subsequent report in the New England Journal of Medicine implied that there was a positive result in the primary efficacy analysis for the entire 487 patient sample. However, this analysis was in fact negative, and the positive result was found only in a secondary analysis of the subgroup of patients who received treatment within 8 hours. In addition, that subgroup apparently had only 62 patients taking methylprednisolone and 67 receiving placebo. The NASCIS II and III reports embody specific choices of statistical methods that have strongly shaped the reporting of results but have not been adequately challenged or or even explained. These studies show statistical artifacts that call their results into question. In NASCIS II, the placebo group treated before 8 hours did poorly, not only when compared with the methylprednisolone group treated before 8 hours but even when compared with the placebo group treated after 8 hours. Thus, the positive result may have been caused by a weakness in the control group rather than any strength of methylprednisolone. In NASCIS III, a randomization imbalance occurred that allocated a disproportionate number of patients with no motor deficit (and therefore no chance for recovery) to the lower dose control group. When this imbalance is controlled for, much of the superiority of the higher dose group seems to disappear. The NASCIS group's decision to admit persons with minor SCIs with minimal or no motor deficit not only enables statistical artifacts it complicates the interpretation of results from the population actually sampled. Perhaps one half of the NASCIS III sample may have had at most a minor deficit. Thus, we do not know whether the results of these studies reflect the severely injured population to which they have been applied. The numbers, tables, and figures in the published reports are scant and are inconsistently defined, making it impossible even for professional statisticians to duplicate the analyses, to guess the effect of changes in assumptions, or to supply the missing parts of the picture. Nonetheless, even 9 years after NASCIS II, the primary data have not been made public. The reporting of the NASCIS studies has fallen far short of the guidelines of the ICH/FDA and of the Evidence-based Medicine Group. Despite the lucrative "off label" markets for methylprednisolone in SCI, no Food and Drug Association indication has been obtained. There has been no public process of validation. These shortcomings have denied physicians the chance to use confidently a drug that many were enthusiastic about and has left them in an intolerably ambiguous position in their therapeutic choices, in their legal exposure, and in their ability to perform further research to help their patients.

Acute Disease↗

The use of food consumption data in assessments of exposure to food chemicals including the application of probabilistic modelling.

Emphasis on public health and consumer protection, in combination with globalisation of the food market, has created a strong demand for exposure assessments of food chemicals. The food chemicals for which exposure assessments are required include food additives, pesticide residues, environmental contaminants, mycotoxins, novel food ingredients, packaging-material migrants, flavouring substances and nutrients. A wide range of methodologies exists for estimating exposure to food chemicals, and the method chosen for a particular exposure assessment is influenced by the nature of the chemical, the purpose of the assessment and the resources available. Sources of food consumption data currently used in exposure assessments range from food balance sheets to detailed food consumption surveys of individuals and duplicate-diet studies. The fitness-for-purpose of the data must be evaluated in the context of data quality and relevance to the assessment objective. Methods to combine the food consumption data with chemical concentration data may be deterministic or probabilistic. Deterministic methods estimate intakes of food chemicals that may occur in a population, but probabilistic methods provide the advantage of estimating the probability with which different levels of intake will occur. Probabilistic analysis permits the exposure assessor to model the variability (true heterogeneity) and uncertainty (lack of knowledge) that may exist in the exposure variables, including food consumption data, and thus to examine the full distribution of possible resulting exposures. Challenges for probabilistic modelling include the selection of appropriate modes of inputting food consumption data into the models.

Consumer Product Safety↗

Interventions for the treatment of burning mouth syndrome: a systematic review.

AIMS: To carry out a systematic review of previous studies to determine the effectiveness of any intervention vs placebo for relief of symptoms and improvement in quality of life of patients with burning mouth syndrome (BMS) and to assess the quality of the studies. METHODS: Electronic databases, conference proceedings, and bibliographies of identified publications were searched (up to September 2001) to identify relevant literature, irrespective of language of publication. Randomized controlled trials and controlled clinical trials of interventions used for the treatment of BMS in comparison to a placebo were included. The primary outcome was relief of burning/discomfort. The screening of studies, validity assessment, and data extraction were undertaken independently and in duplicate. Since statistical pooling of data was inappropriate, a qualitative assessment was undertaken. RESULTS: Seven trials, evaluating antidepressants, cognitive behavioral therapy, analgesics, hormone replacement therapy, and vitamin complexes, met the inclusion criteria. None of the trials was able to provide conclusive evidence of effectiveness. However, cognitive behavioral therapy may be beneficial in reducing the intensity of the symptoms. CONCLUSION: Given that the research evidence is, as yet, unable to provide clear, conclusive evidence of an effective intervention, clinicians need to provide support and understanding when dealing with BMS sufferers. Psychological interventions that help patients to cope with symptoms may be of some use, but promising and new approaches to treatment still need to be evaluated in good-quality randomized controlled trials.

Analgesics, Non-Narcotic↗

The effects of an outpatient practice guideline at a teaching hospital: a prospective pilot study.

Practice guidelines (PGs) are becoming increasingly important in modern medicine. To study the effects of a PG, we performed a pilot study at a large, urban, public teaching hospital according to a prospective, observational research design with both concurrent and historic controls. Specifically, we studied the effects of a multidisciplinary PG for pediatric outpatient tonsillectomy and adenoidectomy on the process of health-care delivery. Variables in the health-care process included patient compliance with clinic and surgery appointments, surgery time, operating room turnover, time in recovery room, unplanned admission rate, patient compliance with postoperative follow-up, provider compliance with guidelines, and hospital charges. Patients in the PG were found to have fewer preoperative laboratory tests, decreased duplication of services, and shorter operating room turnover times. Provider compliance with the PG varied by service and was intermittent at first but improved gradually. There was a trend toward improved compliance with postoperative follow-up in patients in the PG. Provider opinions concerning the guideline were positive. This pilot study demonstrates several advantages and disadvantages of the use of PGs in the outpatient setting and in a teaching hospital.

Adenoidectomy↗

The reporting of theoretical health risks by the media: Canadian newspaper reporting of potential blood transmission of Creutzfeldt-Jakob disease.

BACKGROUND: The media play an important role at the interface of science and policy by communicating scientific information to the public and policy makers. In issues of theoretical risk, in which there is scientific uncertainty, the media's role as disseminators of information is particularly important due to the potential to influence public perception of the severity of the risk. In this article we describe how the Canadian print media reported the theoretical risk of blood transmission of Creutzfeldt-Jakob disease (CJD). METHODS: We searched 3 newspaper databases for articles published by 6 major Canadian daily newspapers between January 1990 and December 1999. We identified all articles relating to blood transmission of CJD. In duplicate we extracted information from the articles and entered the information into a qualitative software program. We compared the observations obtained from this content analysis with information obtained from a previous policy analysis examining the Canadian blood system's decision-making concerning the potential transfusion transmission of CJD. RESULTS: Our search identified 245 relevant articles. We observed that newspapers in one instance accelerated a policy decision, which had important resource and health implication, by communicating information on risk to the public. We also observed that newspapers primarily relied upon expert opinion (47 articles) as opposed to published medical evidence (28 articles) when communicating risk information. Journalists we interviewed described the challenges of balancing their responsibility to raise awareness of potential health threats with not unnecessarily arousing fear amongst the public. CONCLUSIONS: Based on our findings we recommend that journalists report information from both expert opinion sources and from published studies when communicating information on risk. We also recommend researchers work more closely with journalists to assist them in identifying and appraising relevant scientific information on risk.

Bibliometrics↗

A systematic review of the skeletal effects of estrogen therapy in postmenopausal women. I. An assessment of the quality of randomized trials published between 1977 and 1995.

PURPOSE: To examine the quality of published randomized controlled trials of the effects of estrogen treatment on fracture risk and measures of bone mass. DATA SOURCES: Articles on estrogen treatment for osteoporosis published between 1977 and 1995 were identified by searching Medline and Excerpta Medica databases and bibliographies of original papers and published reviews. STUDY SELECTION: Studies selected were randomized controlled trials of the efficacy of estrogens in preventing loss of bone mass or fractures in postmenopausal women. DATA EXTRACTION: Data extraction and quality assessment were performed in duplicate, with assistance of a manual. Raters were blinded as to authors and their affiliations and the publication details. RESULTS: Of 99 eligible randomized controlled trials published between 1977 and 1995, eight included no extractable data, and 23 contained results that were published in duplicate. Total quality scores increased over time, but this was accounted for by improvements only in the measurement technologies used to estimate bone mineral content or density. There was no improvement in the quality of randomization methods, the extent to which withdrawals were accounted for, or in the baseline comparability of treated and control patients. Neither sample sizes nor durations of follow-up increased over time. CONCLUSIONS: This body of literature fails to address whether estrogen therapy reduces fracture rates, and does not allow for comparison of the effects of different active therapies on change in bone density. Although there were improvements in the techniques for estimating bone mass and delivering estrogen treatment, the studies published in the 1990s were no more informative for making clinical or policy decisions than those published in the 1970s.

Adult↗

National drug formularies: lessons from Latin America.

Although pharmaceuticals comprise up to 40% of the health care budget in developing countries, the majority of the population does not have access to many of the essential drugs needed to treat prevalent diseases. This situation demands the development of a national formulary of essential drugs for the public sector. The approach used in developing countries is to select drugs of choice for the treatment of prevalent morbidities and avoid therapeutic duplication, unacceptably dangerous drugs, or drugs of unproven efficacy. Drugs are selected based on a review of the prevalent morbidities, health care worker training, patient characteristics, and efficacy/risk information resulting from scientifically sound studies. An added component to the formulary is the inclusion of concise, unbiased prescribing information for each drug selected. A number of product selection guidelines were proven to be effective in establishing and maintaining an essential drug formulary for developing countries. These guidelines include: 1. Selection of drugs with proven efficacy and acceptable risk; 2. Selection of minimum number of drugs needed to treat the prevalent diseases; 3. Inclusion of new products only if they are found to have distinct advantages over products currently in use; 4. Inclusion of combination products only when they provide true benefit over single ingredients; 5. Selection of drugs with clear "drug of choice" indications for prevalent diseases; 6. Evaluation of the administrative and cost impact of products; and 7. Selection of drugs with established high quality.

Developing Countries↗

When are studies adequate for regulatory purposes? View of one regulated.

The question of adequacy of studies for regulatory purposes has been debated for years. Nine questions need answers to determine adequacy: (1) Does the study deal with a defined problem or a defined segment of it? (2) Do the study data justify the conclusions drawn? (3) Were appropriate statistical analyses used? Is there evidence of bias versus objectivity in the collection or analysis of data? (4) Does the study support, supplement (or complement) or refute information in the literature? Is the study truly new information? (5) Does the study conform to the Interagency Regulatory Liaison Group (IRLG) guidelines for documentation of Epidemiologic Studies? (6) Does the study stand up to peer review? (7) Have other investigators been able to confirm the findings by duplicating the study? (8) Is the study acceptable or can it be made acceptable for publication in a reputable scientific journal? (9) Is the problem of such magnitude or significance that regulation is required? Because there is no such thing as a risk-free environment or absolute safety and there is no definitive "yes" answer to each of the questions, the regulated would hope--yes, insist--that the regulators exercise judgement with great skill in promulgation of rules or regulations. The application of safety factors and the determination of acceptable levels of risk should be social decisions. A discussion of instances where the "regulated" believes that studies have not been adequate, or others habe been ignored, or misinterpreted for regulatory purposes in included.A method of settling controversial questions to eliminate the litigation route is proposed. Judgment which is so often eliminated by regulation needs to find its way back into the regulatory process. The regulated recognize the need for regulations. However, when these regulations are based on less than good scientific judgment, harm will be done to the regulatory process itself in the long run.

Air Pollutants↗

Selecting the language of the publications included in a meta-analysis: is there a Tower of Babel bias?

Although they usually claim a very thorough search to retrieve every pertinent work, most meta-analyses published in English restrict their search to papers which were also published in English. We reviewed all the meta-analyses printed from 1 January 1991 to 1 April 1993 in 8 medical journals published in English and selected those who stated linguistic restrictions for inclusion in the analysis. The computerized search methods used in these meta-analyses were then duplicated looking specifically for publications written in the excluded languages. Each meta-analysis was then redone with identical statistical tests to determine if its conclusions would have been different if the paper(s) absent only for linguistic reasons had been included. A total of 36 meta-analyses of which 28 had language restrictions were identified. The computer searches yielded 19 papers scientifically acceptable but excluded for linguistic reasons. Eleven of these articles were retained as having the potential to modify their corresponding 7 meta-analyses. One meta-analysis which concluded that selective decontamination of the digestive tract in intensive care units did not produce a significant change in mortality between treatment and control patients (OR 0.70; 95% CI 0.45-1.09) would have arrived at a different conclusion (OR 0.67; 95% CI 0.47-0.95) if a paper written in German in a Swiss journal had been included in the analysis. Our study demonstrates that, in at least one out of 36 consecutive meta-analyses the exclusion of papers for linguistic reasons produced results different from those which would have been obtained if this exclusion criteria had not been used.

Clinical Trials as Topic↗

Perioperative allogeneic blood transfusion does not cause adverse sequelae in patients with cancer: a meta-analysis of unconfounded studies.

BACKGROUND: There is controversy over whether perioperative allogeneic red blood cell transfusions are associated with an increased risk of cancer recurrence, postoperative infection or death in patients with cancer undergoing surgery. METHODS: A systematic meta-analysis was performed to answer this question. Studies were identified from electronic databases (Medline 1966-1997, Cancerlit 1983-1997, Current Contents, Cinahl 1982-1996, Healthstar 1990-1997, Bioabstracts 1990-1996 and Embase), by hand search of the bibliographies of identified studies and relevant journals, and by contact with experts in the field. All randomized controlled trials or prospective cohort studies with active comparator controls (autologous or leucocyte-depleted allogeneic blood) were eligible for inclusion if they reported on mortality, infection or recurrence rate in patients with cancer undergoing potentially curative surgical resection. The validity of the identified studies was assessed by means of a standardized scale, and data abstraction was carried out by two investigators independently. A random effects model was used for data synthesis. RESULTS: Of the 2172 references identified, only 17 studies fulfilled the inclusion criteria. After exclusion of duplicate publications, six randomized controlled trials and two prospective cohort studies with appropriate concurrent controls were included in the analysis. The summary risk ratios were 0.95 (95 per cent confidence interval (c.i.) 0.79-1.15) for all-cause mortality and 1.06 (95 per cent c.i. 0.88-1.28) for cancer recurrence, the two endpoints that were appropriate to combine statistically. There was significant heterogeneity (explainable by differences in study design and patient characteristics) in the postoperative infection data and the summary risk ratio was 1.00 (95 per cent c.i. 0.76-1.32) for the four studies that were appropriate to subject to meta-analysis. Given the sample sizes of these eight studies, this meta-analysis had insufficient power to detect a relative difference of less than 20 per cent in the frequency of death, cancer recurrence or infection between the allogeneic and control transfusion arms. CONCLUSION: Although more studies are required before a definitive statement can be made, at this time there is no evidence that allogeneic blood transfusion increases the risk of clinically important adverse sequelae in patients with cancer undergoing surgery.

Cohort Studies↗

Effect of aerosolization on culturability and viability of gram-negative bacteria.

Estimations of the bacterial content of air can be more easily made now than a decade ago, with colony formation the method of choice for enumeration of airborne bacteria. However, plate counts are subject to error because bacteria exposed to the air may remain viable yet lose the ability to form colonies, i.e., they become viable but nonculturable. If airborne bacteria exhibit this phenomenon, colony formation data will significantly underestimate the bacterial populations in air samples. The objective of the study reported here was to determine the effect of aerosolization on viability and colony-forming ability of Serratia marcescens, Klebsiella planticola, and Cytophaga allerginae. A collision nebulizer was used to spray bacterial suspensions into an aerosol chamber, after which duplicate samples were collected in all-glass impingers over a 4-h period. Humidity was maintained at ca. 20 to 25%, and temperature was maintained at 20 to 22 degrees C for each of two replicate trials per microorganism. Viability was determined by using a modified direct viable count method, employing nalidixic acid or aztreonam and p-iodonitrotetrazolium violet (INT). Cells were stained with acridine orange and observed by epifluorescence microscopy to enumerate total and viable cells. Viable cells were defined as those elongating in the presence of antibiotic and/or reducing INT. CFU were determined by plating on tryptic soy agar and R2A agar. It was found that culture techniques did not provide an adequate description of the bacterial burdens of indoor air (i.e., less than 10% of the aerosolized bacteria were capable of forming visible colonies). It is concluded that total cell count procedures provide a better approximation of the number of bacterial cells in air and that procedures other than plate counting are needed to enumerate bacteria in aerosol samples, especially if the public health quality of indoor air is to be estimated.

Aerosols↗

Selective dissemination and indexing of scientific information.

Selective dissemination of information to individuals provides a new and promising method for keeping abreast of current scientific information. Since SDI services are directed to the information needs of each individual, they are a significant step beyond grouporiented services and products, which require considerable expenditure of effort by each user as he sorts useful information from trash. However, SDI systems do require a high degree of precision in matching scientists against documents. They must operate more efficiently and economically than many current systems which occasionally provide a useful item of information to users. To meet these stringent requirements for quality, precision, efficiency, and economy, more research must be devoted to comparing and improving indexing methods, which are the basic component of all information storage and retrieval systems. It is incredible that so much money has been spent on the development and operation of scientific information systems before basic data on the comparative performance of various indexing methods have been gathered, analyzed, and confirmed by multiple investigators. The design of an effective information system would seem to require this type of basic knowledge, just as basic properties of alternative materials must be known before an engineer can design a building, bridge, or factory. Yet, except for the few studies mentioned in the previous section, research on indexing methods has been greatly neglected. Bourne's comment about studies of indexing languages is still an appropriate description of the situation: "In almost all the experimental reports, the investigator worked with an indexing language different than that of other experimenters. Consequently, no one has ever had his test results verified, or expanded, or made more precise by another experimenter" (47). Most existing information systems are based on keyword indexing, with concepts broken into isolated terms during input operations and recombined to synthesize the original concept during search and retrieval. Such systems tend to involve imprecise indexing, with a high level of "noise" in retrieved documents, difficult search strategy involving extensive post-coordination, and lengthy, complex computer manipulations. This situation reflects the fact that many producers of indexed data originally focused the design of their systems on the production of a published product with entries printed under short, concise index headings. Production of magnetic tapes as a by-product of the publication process, and their use for retrospective searching or for SDI services, was a much later development, almost an afterthought. Yet use of these tapes is growing so rapidly that it may be time to redesign the tape-producing systems, with ease of tape use for SDI services and retrospective searching as the primary consideration, and with publication of abstract and index bulletins or title listings relegated to secondary importance (49). The use of keywords to index documents creates a high degree of disorganization in information search and retrieval operations: Information is scattered under the many different terms that can be used to index different aspects of a concept. If the large-scale, comprehensive abstracting and indexing services were based on enumerative classifications with assignment of documents to logical hierarchical categories at the time of initial indexing, then many of the specialized information centers (50) and the 1300 abstracting and indexing services (3) would be unnecessary, and much of the reindexing and reprocessing of documents, the repackaging and reworking of abstracts and index data, and the resulting overlap and duplication characteristic of current information processing could be terminated. Partly because of the disorganization resulting from keyword indexing, the cost of a 5-year retrospective search of information on just one data base on magnetic tapes is a major investment (16). The effort and cost required to find a few items of useful information scattered among 1,285,000 abstracts indexed on 116 full reels of magnetic tape (11 million characters per reel) which will be needed for the 5-year Eighth Collective Index to Chemical Abstracts (1967-1971) (51) staggers the imagination. In contrast, when HICLASS systems based on enumerative hierarchical classifications are used, concepts that might be useful for later retrieval are identified and related items of information are grouped together during the indexing process. These enumerative classifications, with single-hit matching, make it possible to index and retrieve ideas as intact units and to perform simple sequential searches of the very small segment of a file that deals with a given topic (31). The experiments at both the Science Information Exchange and the National Cancer Institute, as described in this article, demonstrate that automated HICLASS systems are feasible and can operate at a very satisfactory level of performance. Although considerable effort may be required for the development and constant updating of detailed enumerative classifications, HICLASS categories may facilitate organization of data at the time of input, improve the precision of matching documents with users, and greatly simplify search logic and computer manipulations. If so, then output savings and performance would more than justify input costs, and the development and use of enumerative classifications would be a better solution to information problems than the current keyword-and-coordination approach. It is time to think beyond the ease of the single input step in information systems and to take a hard look at ways of easing retrieval problems for the multitude of information systems that process the indexed data (52). Indexing effort is expended only once, whereas search and retrieval effort is required by every user of a system. If information were better analyzed and organized during input operations, if more basic research were devoted to the effect of indexing methods on the performance of information systems, and if more emphasis were placed on the quality and usefulness of retrieved information, then the magnitude of problems related to the storage and retrieval of scientific information might be considerably reduced.

Abstracting and Indexing↗

A novel technique for transforming the theft of mortal human cells into praiseworthy federal policy.

A revolution has occurred in the attitude of biologists toward their intellectual property rights. What today is patentable and highly profitable was, 20 years ago, unpatentable and given away for nothing. The history of this revolution began in the early 1960s when we made the first effort to have self-duplicating cell strains patented. The application was denied because patent law at that time did not include living matter. Because of the demand for our normal human diploid cell strain, WI-38, by NIH grantees, NIH support was provided to distribute WI-38 gratis to hundreds of recipients. These included vaccine and cell manufacturers who profited enormously from the direct sale of WI-38 or its use as a substrate for many human virus vaccines. When federal support for the distribution of WI-38 ended, but demand did not, I continued to distribute it for costs similar to those made by the American Type Culture Collection. When I took the first initiative and asked NIH to have the then unique question of title to a self-duplicating system resolved, they sent an accountant who accused me of theft of government property. I replied with a lawsuit that, after six years of litigation, we won with an out-of-court settlement. During these six years the United States Supreme Court ruled that living matter could be patented. Also, the biotechnology industry was launched by biologists who, like me, started companies using cells or microorganisms developed with federal support. This use of intellectual property rights by the nascent biotechnology industry was ultimately embraced by the entire biological community and by a directive from the President of the United States. This revolution has now evolved to the point where government biologists themselves may profit from research in federal laboratories, and the NIH itself aggressively seeks private commercial alliances. Universities have also pursued similar alliances to the extent that today the distinction between a research university and a commercial organization is only in the eyes of the Internal Revenue Service.

Biotechnology↗

Does a "Level I Evidence" rating imply high quality of reporting in orthopaedic randomised controlled trials?

BACKGROUND: The Levels of Evidence Rating System is widely believed to categorize studies by quality, with Level I studies representing the highest quality evidence. We aimed to determine the reporting quality of Randomised Controlled Trials (RCTs) published in the most frequently cited general orthopaedic journals. METHODS: Two assessors identified orthopaedic journals that reported a level of evidence rating in their abstracts from January 2003 to December 2004 by searching the instructions for authors of the highest impact general orthopaedic journals. Based upon a priori eligibility criteria, two assessors hand searched all issues of the eligible journal from 2003-2004 for RCTs. The assessors extracted the demographic information and the evidence rating from each included RCT and scored the quality of reporting using the reporting quality assessment tool, which was developed by the Cochrane Bone, Joint and Muscle Trauma Group. Scores were conducted in duplicate, and we reached a consensus for any disagreements. We examined the correlation between the level of evidence rating and the Cochrane reporting quality score. RESULTS: We found that only the Journal of Bone and Joint Surgery - American Volume (JBJS-A) used a level of evidence rating from 2003 to 2004. We identified 938 publications in the JBJS-A from January 2003 to December 2004. Of these publications, 32 (3.4%) were RCTs that fit the inclusion criteria. The 32 RCTs included a total of 3543 patients, with sample sizes ranging from 17 to 514 patients. Despite being labelled as the highest level of evidence (Level 1 and Level II evidence), these studies had low Cochrane reporting quality scores among individual methodological safeguards. The Cochrane reporting quality scores did not differ significantly between Level I and Level II studies. Correlations varied from 0.0 to 0.2 across the 12 items of the Cochrane reporting quality assessment tool (p > 0.05). Among items closely corresponding to the Levels of Evidence Rating System criteria assessors achieved substantial agreement (ICC = 0.80, 95% CI:0.60 to 0.90). CONCLUSION: Our findings suggest that readers should not assume that 1) studies labelled as Level I have high reporting quality and 2) Level I studies have better reporting quality than Level II studies. One should address methodological safeguards individually.

Bibliometrics↗