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The biotechnology industry has become firmly established over the past twenty years and gene patents have played an important part in this phenomenon. However, concerns have been raised over the patentability of human genetic material, through public protests and international statements, but to little effect. Here we discuss some of these concerns, the patent authorities' response to them, and ways in which to address these issues and to move the debate forward using current legal structures.

ContextDespite federal regulations on faculty conflicts of interest in federally funded research, academic-industry ties are common, and evidence exists that financial considerations bias the research record. Public scrutiny of these ties is increasing, especially in cases where researchers have financial interests in the corporate sponsors of their clinical research.ObjectiveTo review policies on conflict of interest at major biomedical research institutions in the United States.DesignCross-sectional survey and content analysis study conducted from August 1998 to February 2000.Setting and ParticipantsThe 100 US institutions with the most funding from the National Institutes of Health in 1998 were initially sampled; policies from 89 institutions were available and included in the analysis.Main Outcome MeasuresProcess for disclosure, review, and management of conflicts of interest and specified management strategies or limitations, according to the institutions' faculty/staff conflict of interest policies.ResultsContent of the conflict of interest policies varied widely across institutions. Fifty-five percent of policies (n = 49) required disclosures from all faculty while 45% (n = 40) required them only from principal investigators or those conducting research. Nineteen percent of policies (n = 17) specified limits on faculty financial interests in corporate sponsors of research, 12% (n = 11) specified limits on permissible delays in publication, and 4% (n = 4) prohibited student involvement in work sponsored by a company in which the faculty mentor had a financial interest.ConclusionsMost policies on conflict of interest in our sample of major research institutions in the United States lack specificity about the kinds of relationships with industry that are permitted or prohibited. Wide variation in management of conflicts of interest among institutions may cause unnecessary confusion among potential industrial partners or competition among universities for corporate sponsorship that could erode academic standards. It is in the long-term interest of institutions to develop widely agreed-on, clear, specific, and credible policies on conflicts of interest.

The Internet is a promising and popular tool for the global dissemination of health information to the public. According to one estimate, “health sites draw two thirds of all online users at least once.”1 Unfortunately, the power of the Internet to facilitate quick, inexpensive, and worldwide publication is also a weakness when it comes to information about health. Distinctions between trained medical professionals and quacks, tested drugs and untested compounds, and advertisements and content are difficult to make. Furthermore, the global nature of the Internet defies most current nation-specific laws regulating the practice of medicine or sales of health-related products based on unverified health claims.2 The use of the Internet has encouraged the blurring of distinctions between content areas and advertising. Criticism of the well-traveled health information web site, drkoop. com, started by the former US Surgeon General C Everett Koop,3 however, illustrates why such ambiguity is a problem for health care professionals and why the criticisms bring to mind images of foxes and henhouses.

Este trabajo corresponde a la traducción al español de la Colaboración Especial publicada en The Journal of the American Medical Association en agosto de 1996, junto con el editorial How to report Randomized Controlled Trials. The Consort Statement, publicada en el mismo número. En ella se describe la elaboración de las Normas Consolidadas para la elaboración de los Informes de los Ensayos Clínicos Controlados, por un grupo de trabajo formado por los componentes del grupo SORT y del Grupo de Trabajo Asilomar, junto con el director de una revista y el autor del informe de un ensayo clínico. El trabajo se realizó mediante un proceso Delphi y el resultado fue una lista de comprobación (checklist) y un diagrama de flujo. La primera está compuesta por 21 puntos que se refieren principalmente a los métodos, resultados y discusión del informe de un ensayo clínico controlado, identificándose la información necesaria para poder evaluar la validez interna y externa del ensayo, valorándose la mejora como positiva, tanto para los pacientes, como para los editores de las revistas y los revisores de las mismas. This summary corresponds to the translation into Spanish of the Special Communication published in the Journal of the American Medical Association in August 1996, along with the editorial published in the same issue "How to report Randomized Controlled Trials. The Consort Statement". It describes the Consolidated Standars for Preparation of Controlled Clinical Trials, prepared by a work group made up of members of the SORT Group and of the Asilomar Work Group, along with the editor of a magazine and the author of the report on a clinical trial. The work was carried out by means of a Delphy process and the result was a check list and a process diagram. The check list is made up of 21 items that mainly refer to methods, results and discussions on the report of a controlled clinical trial, identifying the necessary information in order to be able to evaluate the internal and external value of the report, judging the improvement to be positive for the patient, the editors and the reviewers of the magazines.

What should happen when a researcher sees a potential health problem in a brain scan from a research subject?

The finding of fraud associated with the Hwang et al. stem cell reports raises issues that need careful scrutiny: authorship, ethics, funding, and science education.

Dr. Woo-Suk Hwang and his colleagues in South Korea have achieved tremendous breakthroughs in the field of stem cell research, particularly with their use of somatic cell nuclear transfer (SCNT). T...

Stem cell research on human embryonic stem cells derived through use of oocytes originally obtained specifically for research and not for reproductive or medical purposes creates a new class of research subject. In this Policy Forum, the authors explore the ethical issues for those who perform such studies and for research donors. Healthy oocyte donors differ from traditional research subjects in that neither they nor their tissues are the direct objects of study but their tissues are used to create materials for research. Yet they are exposed to significant risks and have no prospect of direct benefit. Researchers in the U.S. who conduct such studies in other countries should follow U.S. guidelines such as those recently released by the National Research Council-Institute of Medicine, even if they are not required by law, because of the special ethical considerations raised by this new category of research subject. The informed consent process for donors should not minimize the risks of oocyte procurement just because the donors are not giving their oocytes for reproductive purposes, or portray stem cell transplantation research as an existing therapy.

Now that the NIH has reached an agreement with Henrietta Lacks's family concerning the use of the HeLa cell line, what lessons can we learn about informed consent and the unforeseen use of biological samples?

In Figure 1 the genes involved in pigmentation are shown as “SLC24A5, SLC42A2”. They should be “SLC24A5, SLC45A2”. Similarly, in the legend for Figure 1, line 8, it reads:“In European populations, genes that affect skin pigmentation (SLC24A5 and SLC42A2) have undergone positive selection.”It should read:“In European populations, genes that affect skin pigmentation (SLC24A5 and SLC45A2) have undergone positive selection.”We apologize to the readers of this article for this error.

Background The translation of novel genomic technologies from bench to bedside enjoins the comprehensive consideration of the perspectives of all stakeholders who stand to influence, or be influenced by, the translational course. Non-invasive prenatal aneuploidy testing that utilizes cell-free fetal DNA (cffDNA) circulating in maternal blood is one example of an innovative technology that promises significant benefits for its intended end users; however, it is currently uncertain whether it will achieve widespread clinical implementation. We conducted qualitative interviews with 18 diverse stakeholders in this domain, including prospective users of the technology and healthcare personnel, researchers and developers, and experts in social, legal, and regulatory aspects of genetic technology, and a pilot survey of 62 obstetric healthcare providers. Analysis of interview and survey data was combined with a review of the proceedings of a full-day, multidisciplinary conference on the topic and published scientific and ethics literature surrounding this and other relevant technologies. Discussion We constructed potential pathways for technological implementation, identified broad stakeholder classes party to these translational processes, and performed a preliminary assessment of the viewpoints and interrelations among these diverse stakeholders. Some of the stakeholders whose priorities are critical to understand and integrate into translation include pregnant women and their families; healthcare providers; scientists, their institutions or companies, and the funding agencies that support them; regulatory and judicial bodies; third-party payers; professional societies; educational systems; disability rights communities; and other representatives from civil society. Stakeholder interviews, survey findings, and conference proceedings add complexity to these envisioned pathways and also demonstrate a paramount need to incorporate an iterative stakeholder analysis early and throughout the translational endeavor. We believe that the translational framework that we have developed will help guide crucial future stakeholder mapping and engagement activities for cffDNA aneuploidy testing and inform novel methods of technology assessment for other developments in the growing field of genomic medicine. Summary Mapping potential pathways for implementation and exploring the attitudes and interrelations of diverse stakeholders may lead to more effective translation of a novel method of prenatal aneuploidy testing.

Myosin heavy chain (MyHC) isoforms show a striking diversity of expression patterns during mammalian development. Using a set of monoclonal antibodies that recognize different epitopes on myosin heavy chain isoforms we show that there exist in human and rat skeletal muscle at least three isoforms of slow twitch myosin heavy chain. To facilitate a comparison of our results to others obtained using different antibodies or species, we have identified cDNAs encoding the epitopes recognized by the three slow antibodies. Using these reagents, we show that the onset of expression of three slow MyHC isoforms is temporally distinct during early gestation. This result suggests that a sequence of MyHC transitions plays an important role in determining muscle fiber function at fetal, neonatal, and adult stages.

Background Research ethics consultation programs are being established with a goal of addressing the ethical, societal, and policy considerations associated with biomedical research. A number of these programs are modelled after clinical ethics consultation services that began to be institutionalized in the 1980s. Our objective was to determine biomedical science researchers' perceived need for and utility of research ethics consultation, through examination of their perceptions of whether they and their institutions faced ethical, social or policy issues (outside those mandated by regulation) and examination of willingness to seek advice in addressing these issues. We conducted telephone interviews and focus groups in 2006 with researchers from Stanford University and a mailed survey in December 2006 to 7 research universities in the U.S. Findings A total of 16 researchers were interviewed (75% response rate), 29 participated in focus groups, and 856 responded to the survey (50% response rate). Approximately half of researchers surveyed (51%) reported that they would find a research ethics consultation service at their institution moderately, very or extremely useful, while over a third (36%) reported that such a service would be useful to them personally. Respondents conducting human subjects research were more likely to find such a service very to extremely useful to them personally than respondents not conducting human subjects research (20% vs 10%; chi2 p

The availability of personalized genomic tests, ordered directly by consumers, is rapidly growing. These tests are unlike other genetic or biochemical tests in the sheer amount of data they provide, but interpretation of these genome-wide analyses for health remains uncertain because of the lack of information about environmental and other factors, and because for the vast majority of genetic loci the associations with disease are weak. Although these tests could provide value to customers by offering tools for social networking or genealogy, there are questions about whether and how to regulate these tests and about the extent to which they provide medical information.

We are a multidisciplinary group of Stanford faculty who propose ten principles to guide the use of racial and ethnic categories when characterizing group differences in research into human genetic variation.

On 31 May 2007, James Watson was handed a miniature hard drive containing his personal genome sequence, which was subsequently uploaded onto publicly accessible databases. Craig Venter’s personal genome was published a few months later (1). These projects represent research milestones. They also present an opportunity to examine the ethical, social, and clinical implications of personal genomics.

This work was supported in part by grants from the Greenwall Foundation, the Charles E. Culpeper Foundation, the National Institutes of Health (NIH), Department of Energy, and Veterans Administration Consortium on Informed Consent Research (all to P.S. and J.F.M.) and from the NIH National Human Genome Research Institute, Ethical, Legal, and Social Implications Branch (to M.K.C. and P.S.). The opinions expressed are solely those of the authors. The authors thank Arthur Caplan, Sheri Alpert, Barbara Weber, and an anonymous referee for comments on earlier versions of the manuscript.

Alleviating health disparities in the United States is a goal with broad support. Medical research undertaken to achieve this goal typically adopts the well-established perspective that racial discrimination and poverty are the major contributors to unequal health status. However, the suggestion is increasingly made that genetic research also has a significant role to play in alleviating this problem, which likely overstates the importance of genetics as a factor in health disparities. Overemphasis on genetics as a major explanatory factor in health disparities could lead researchers to miss factors that contribute to disparities more substantially and may also reinforce racial stereotyping, which may contribute to disparities in the first place. Arguments that promote genetics research as a way to help alleviate health disparities are augmented by several factors, including research funding initiatives and the distinct demographic patterns of health disparities in the United States.

Race The Power of an Illusion. Larry Adelman, Executive Producer. California Newsreel, San Francisco. On PBS, Thursdays, 24 April to 8 May 2003. Companion Web site, www.pbs.org/race This three-part series on PBS examines the idea of race from the varied perspectives of science, history, and our social institutions.

A study to examine strategies and practices relating to the patenting and licensing of genetic invention was undertaken. Technology transfer and licensing executives from 46 nonprofit and for-profit institutions were interviewed. The results suggest that (i) nonprofit institutions receive more invention disclosures than firms, but are less likely to file patent applications; and (ii) nonprofits are slightly more likely to license their patented genetic inventions and are significantly more likely to do so on an exclusive basis. This Policy Forum raises questions about the effects of federal technology transfer policy.

In his article “Allen Roses: From ‘street fighter’ to corporate insider” (News & Comment, 15 May, p. [1001][1]), Eliot Marshall notes (p. [1004][2]) that Roses disagreed with a group of experts at Stanford who had concluded that widespread molecular testing for late-onset Alzheimer's disease

Context.— In a previous study, we found that masking success was higher at a journal that masked reviewers to author identity. We hypothesized that masking policy or other factors could be associated with masking success. Objectives.— To evaluate differences in success of masking reviewers to author identity at 7 biomedical journals and to identify factors associated with these differences. Design.— Written questionnaire. Participants.— Reviewers at 3 journals with a long-standing policy of masking author identity (Annals of Emergency Medicine, Epidemiology, and Journal of the American Geriatrics Society) and 4 journals without a policy of masking author identity (Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology). Main Outcome Measures.— Masking success (percentage of reviewers successfully masked) and reviewer characteristics associated with masking. Results.— There was no significant difference in masking success between journals with a policy of masking (60%) and those without (58%) (P = .92). We found no association between masking success and a policy of masking when adjusted for the reviewer characteristics of age, sex, years of reviewing experience, number of articles published, number of articles reviewed, percentage of time spent in research, editorial experience, or academic rank (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.64-2.8; P = .43). In multivariable analysis of reviewer characteristics, reviewers spending a greater percentage of time in research, the only significant predictor of masking success, were less likely to be successfully masked (OR, 1.01; 95% CI, 1.00-1.02) (P = .04). Conclusions.— Masking success appears unrelated to a journal policy of masking, but is associated with reviewers’ research experience and could be affected by other characteristics. Using reviewers with less research and reviewing experience might increase masking success, but the effect on review quality is unknown.

Context.—All authors may not be equal in the eyes of reviewers. Specifically, well-known authors may receive less objective (poorer quality) reviews. One study at a single journal found a small improvement in review quality when reviewers were masked to author identity.Objectives.—To determine whether masking reviewers to author identity is generally associated with higher quality of review at biomedical journals, and to determine the success of routine masking techniques.Design and Setting.—A randomized controlled trial performed on external reviews of manuscripts submitted to Annals of Emergency Medicine, Annals of Internal Medicine, JAMA, Obstetrics & Gynecology , and Ophthalmology .Interventions.—Two peers reviewed each manuscript. In one study arm, both peer reviewers received the manuscript according to usual masking practice. In the other arm, one reviewer was randomized to receive a manuscript with author identity masked, and the other reviewer received an unmasked manuscript.Main Outcome Measure.—Review quality on a 5-point Likert scale as judged by manuscript author and editor. A difference of 0.5 or greater was considered important.Results.—A total of 118 manuscripts were randomized, 26 to usual practice and 92 to intervention. In the intervention arm, editor quality assessment was complete for 77 (84%) of 92 manuscripts. Author quality assessment was complete on 40 (54%) of 74 manuscripts. Authors and editors perceived no significant difference in quality between masked (mean difference, 0.1; 95% confidence interval [CI], −0.2 to 0.4) and unmasked (mean difference, −0.1; 95% CI, −0.5 to 0.4) reviews. We also found no difference in the degree to which the review influenced the editorial decision (mean difference, −0.1; 95% CI,−0.3 to 0.3). Masking was often unsuccessful (overall, 68% successfully masked; 95% CI, 58%-77%), although 1 journal had significantly better masking success than others (90% successfully masked; 95% CI, 73%-98%). Manuscripts by generally known authors were less likely to be successfully masked (odds ratio, 0.3; 95% CI, 0.1-0.8). When analysis was restricted to manuscripts that were successfully masked, review quality as assessed by editors and authors still did not differ.Conclusions.—Masking reviewers to author identity as commonly practiced does not improve quality of reviews. Since manuscripts of well-known authors are more difficult to mask, and those manuscripts may be more likely to benefit from masking, the inability to mask reviewers to the identity of well-known authors may have contributed to the lack of effect.

To compare the quality, relevance, and structure of drug studies published in symposium proceedings that are sponsored by drug companies with 1) articles from symposia with other sponsors and 2) articles in the peer-reviewed parent journals of symposium proceedings; and to study the relation between drug company sponsorship and study outcome.Cross-sectional studies of clinical drug studies published in symposium proceedings or their parent medical journals.The proportion of articles with no methods sections (which are necessary to assess quality); methodologic quality and clinical relevance scores; and the proportion of articles with outcomes favoring the drug of interest.Symposia sponsored by single drug companies had more articles without methods sections (10%; 108 of 1064) than did symposia that had other sponsors (3%; 58 of 2314) or symposia that had no mentioned sponsor (2%; 29 of 1663) (P0.001). The mean methodologic quality and relevance scores of articles were similar both by type of sponsorship and between articles published in symposia sponsored by single drug companies and articles from the parent journals. Significantly more articles with drug company support (98%; 39 of 40) than without drug company support (79%; 89 of 112) had outcomes favoring the drug of interest (P = 0.01).Articles in symposia sponsored by single drug companies were similar in quality and clinical relevance to articles with other sponsors and to articles published in the parent journals. Articles with drug company support are more likely than articles without drug company support to have outcomes favoring the drug of interest.

A RANDOMIZED controlled trial (RCT) is the most reliable method of assessing the efficacy of health care interventions.1,2Reports of RCTs should provide readers with adequate information about what went on in the design, execution, analysis, and interpretation of the trial. Such reports will help readers judge the validity of the trial. There have been several investigations evaluating how RCTs are reported. In an early study, Mahon and Daniel3reviewed 203 reports of drug trials published between 1956 and 1960 in theCanadian Medical Association Journal. Only 11 reports (5.4%) fulfilled their criteria of a valid report. In a review of 45 trials published during 1985 in three leading general medical journals, Pocock and colleagues4reported that a statement about sample size was only mentioned in five (11.1%) of the reports, that only six (13.3%) made use of confidence intervals, and that the statistical analyses tended to

Objective. —To develop valid and reliable instruments to assess the methodologic quality and clinical relevance of drug studies. Design. —We developed an instrument to assess the methodologic quality of articles reporting clinical research and an instrument to measure nonmethodologic measures of quality, such as clinical relevance, generalizability, and adherence to ethical standards. Each instrument was pretested by seven independent, masked reviewers and modified based on interrater agreement and content validity of individual items. We determined correlational validity of the final methodologic quality instrument by comparing quality scores assigned to 10 articles by means of our instrument and a previously published one. Participants. —Clinical drug studies published in symposium proceedings and peer reviewed biomedical literature. Main Outcome Measures. —Interrater reliability of overall quality scores, measured by intraclass correlation ( r ) and Kendall's coefficient of concordance (W), and interrater reliability of individual items, by percentage agreement. Main Results. —The interrater reliability of the pretest methodologic quality instrument was high ( r =.89 [95% confidence interval,.73 to.96]; W=0.64). Correlational validity of the final instrument was suggested by the high degree of concordance with another previously published one (W=0.74). The interrater reliability of the pretest clinical relevance instrument was moderate ( r =.41 [95% confidence interval,.18 to.64]; W=0.47). Reviewers confirmed the content validity of both instruments. Conclusions. —The two instruments we developed, one measuring methodologic quality and one measuring clinical relevance of articles reporting clinical research, are reliable, valid, and applicable to a variety of research designs. ( JAMA . 1994;272:101-104)