Completion and Publication Rates of Randomized Controlled Trials in Surgery: An Empirical Study.

OBJECTIVE: To investigate the prevalence of discontinuation and nonpublication of surgical versus medical randomized controlled trials (RCTs) and to explore risk factors for discontinuation and nonpublication of surgical RCTs. BACKGROUND: Trial discontinuation has significant scientific, ethical, and economic implications. To date, the prevalence of discontinuation of surgical RCTs is unknown. METHODS: All RCT protocols approved between 2000 and 2003 by 6 ethics committees in Canada, Germany, and Switzerland were screened. Baseline characteristics were collected and, if published, full reports retrieved. Risk factors for early discontinuation for slow recruitment and nonpublication were explored using multivariable logistic regression analyses. RESULTS: In total, 863 RCT protocols involving adult patients were identified, 127 in surgery (15%) and 736 in medicine (85%). Surgical trials were discontinued for any reason more often than medical trials [43% vs 27%, risk difference 16% (95% confidence interval [CI]: 5%-26%); P = 0.001] and more often discontinued for slow recruitment [18% vs 11%, risk difference 8% (95% CI: 0.1%-16%); P = 0.020]. The percentage of trials not published as full journal article was similar in surgical and medical trials (44% vs 40%, risk difference 4% (95% CI: -5% to 14%); P = 0.373). Discontinuation of surgical trials was a strong risk factor for nonpublication (odds ratio = 4.18, 95% CI: 1.45-12.06; P = 0.008). CONCLUSIONS: Discontinuation and nonpublication rates were substantial in surgical RCTs and trial discontinuation was strongly associated with nonpublication. These findings need to be taken into account when interpreting surgical literature. Surgical trialists should consider feasibility studies before embarking on full-scale trials.

“No fim não vai ficar nada”: exploração dos recursos florestais em Cabo Delgado relatório do trabalho de campo em Namiune, Nkonga e 5º Congresso: Relatório do trabalho de campo nas concessões COMADEL e a FMJ, Cabo Delgado, Novembro de 2010

This report focuses on forest product users in the COMADEL and FMJ forest concessions, Cabo Delgado, as well as the effects of their combined strategies and activities on sustainable use of natural resources and sustainable socio-economic development of the region. The aim is to contribute to understanding the effects of these strategies and activities on forest regeneration, ecosystem services and on resource sustainability. The study examines the role played by the Committees of Natural Resources in forest exploitation. Data obtained from interviews and observations were used to complement and update a variety of existing data from oral and written sources dealing with forest regeneration in Cabo Delgado. These existing materials originate from previous studies conducted in the context of the ESAPP project that started more than two years ago. They include results from Learning for Sustainability workshops (LforS, http://www.cde.unibe.ch/Pages/Project/2/14/Learningfor- Sustainability-Extension-Approach.aspx), as well as field reports, academic studies, management plans used by concessionaires, and others. The interviews and observations took place more or less continuously from the beginning of this phase of the project in 2008. Interviews were systematically conducted with owners of concessions operating in the region, employees of logging companies, residents of villages within the existing concessions, government officials and others. It was not possible to collect information directly from poachers in part due to the illegal nature of their work. Information on these activities was obtained indirectly through members of the Committees of Natural Resources, the concessionaire, and its workers, as well as by observing the traces of extraction – traps, bones and parts of slaughtered animals, tree stumps, material ready for transportation, etc. The main results indicate that extraction by the logging company MITI Ltd. and others acting in the region, by poachers and by other actors – e.g. sawyers using manual saws – put a lot of pressure on marketable species, particularly Millettia stuhlmannii, Afzelia quanzensis and Swartzia madagascariensis. Natural regeneration of forests in northern Cabo Delgado is being compromised by the combination of various extracting activities and uncontrolled fires. MITI Ltd. continued the pattern of exploitation of forest resources that was characteristic of companies operating in the region earlier, such as COMADEL. MITI Ltd. failed to implement the broad range of development and conservation activities encouraged by the new legislation on forest concessions that was created to promote sustainable use of resources.

“Se querem que façamos algo pela floresta tem que nos pagar”: As lógicas da participação dos camponeses nos Comités de Gestão dos Recursos Naturais nos distritos de Palma e Mocimboa da Praia em 2009: Relatório do trabalho de campo em Namiune, Nkonga e 5º Congresso, Maputo, Dezembro de 2010

Our study considers the natural resources of the Miombo forests in Cabo Delgado from a broad ecosystems perspective. Thus, our view goes beyond the disciplinary approaches of forestry, agronomy, biology or zoology, and also of the social sciences, namely anthropology, history, sociology, political science or economics. The present study aims to establish a dialogue and create synergies between Miti Ltd. – the logging company and owner of the forest concessions – as well as government and state structures at the various levels and the communities – through the Committees on Natural Resources – in order to promote the sustainable use of resources and ecosystems. The research methodology we used can broadly be described as moderated transdisciplinary interaction for action-research based on the approach known as Learning for Sustainability (LforS, http://www.cde.unibe.ch/Pages/Project/2/14/Learning-for-Sustainability-Extension-Approach.aspx). The research methods used include: LforS seminars; field work; forests observations focusing, among others, on ecosystems, trees, wildlife, and burned areas; visits to farms; and interviews. We conducted both collective interviews and individual interviews, including with key informants. The main results indicate that members of the Committee on Natural Resources have a dual attitude: their statements defend the paradigm of sustainable use of natural resources as well as their own immediate monetary gain. They are willing to apply the values, concepts and theories of sustainable development that underpin the establishment of Committees on Natural Resources if they are paid for their work or if they can derive direct benefits from it, i.e. if they can earn a salary or allowance. If this does not happen, however, they are willing to allow actors to engage in illegal hunting or logging activities. This dual attitude also exists in relation to forestry operators. If the concession workers pay the committee members in cash or provide goods, they can run their business even if they violate the law. Natural forest regeneration in Nkonga and Namiune already shows the impact of such use. Although there are many saplings that could basically ensure continuous regeneration under sustainable management, repeated burning is damaging the young trees, deforming them and killing a great number of them. Campaigns against uncontrolled fires are ineffective because the administrative and political authorities have a dual attitude as well and are also part of the group that uses resources to their own profit and benefit. There are institutional structures within the administration, populations, and communities to perform regulating functions, create and implement rules, punish offenders, and oversee resource use. However, they feel that since they are not paid for performing these functions, they do not have to do so. This attitude shows a lack of awareness, but also indicates a situation where everyone seeks to derive maximum benefits from existing resource use patterns. Anything goes.

Ethical procedures and patient consent differ in Europe.

BACKGROUND Research ethics approvals, procedures and requirements for institutional research ethics committees vary considerably by country and by type of organisation. OBJECTIVE To evaluate the requirements and procedures of research ethics committees, details of patient information and informed consent based on a multicentre European trial. DESIGN Survey of European hospitals participating in the prospective observational study on chronic postsurgical pain (euCPSP) using electronic questionnaires. SETTING Twenty-four hospitals in 11 European countries. PARTICIPANTS From the 24 hospitals, 23 local investigators responded; 23 answers were analysed. OUTCOME MEASURES Comparison of research ethics procedures and committee requirements from the perspective of clinical researchers. Comparison of the institutions' procedures regarding patient information and consent. Description of further details such as costs and the duration of the approval process. RESULTS The approval process lasted from less than 2 weeks up to more than 2 months with financial fees varying between 0 and 575 &OV0556;. In 20 hospitals, a patient information sheet of variable length (half page up to two pages) was provided. Requirements for patients' informed consent differed. Written informed consent was mandatory at 12, oral at 10 and no form of consent at one hospital. Details such as enough time for consideration, possibility for withdrawal and risks/benefits of participation were provided in 25 to 30% of the institutions. CONCLUSION There is a considerable variation in the administrative requirements for approval procedures by research ethics committees in Europe. This results in variation of the extent of information and consent procedures for the patients involved. TRIAL REGISTRATION euCPSP in Clinicaltrials.gov identifier: NCT01467102; PAIN-OUT in Clinicaltrials.gov identifier: NCT02083835.

A pilot test of the new Swiss regulatory procedure for categorizing clinical trials by risk: A randomized controlled trial

BACKGROUND/AIMS Several countries are working to adapt clinical trial regulations to align the approval process to the level of risk for trial participants. The optimal framework to categorize clinical trials according to risk remains unclear, however. Switzerland is the first European country to adopt a risk-based categorization procedure in January 2014. We assessed how accurately and consistently clinical trials are categorized using two different approaches: an approach using criteria set forth in the new law (concept) or an intuitive approach (ad hoc). METHODS This was a randomized controlled trial with a method-comparison study nested in each arm. We used clinical trial protocols from eight Swiss ethics committees approved between 2010 and 2011. Protocols were randomly assigned to be categorized in one of three risk categories using the concept or the ad hoc approach. Each protocol was independently categorized by the trial's sponsor, a group of experts and the approving ethics committee. The primary outcome was the difference in categorization agreement between the expert group and sponsors across arms. Linear weighted kappa was used to quantify agreements, with the difference between kappas being the primary effect measure. RESULTS We included 142 of 231 protocols in the final analysis (concept = 78; ad hoc = 64). Raw agreement between the expert group and sponsors was 0.74 in the concept and 0.78 in the ad hoc arm. Chance-corrected agreement was higher in the ad hoc (kappa: 0.34 (95% confidence interval = 0.10-0.58)) than in the concept arm (0.27 (0.06-0.50)), but the difference was not significant (p = 0.67). LIMITATIONS The main limitation was the large number of protocols excluded from the analysis mostly because they did not fit with the clinical trial definition of the new law. CONCLUSION A structured risk categorization approach was not better than an ad hoc approach. Laws introducing risk-based approaches should provide guidelines, examples and templates to ensure correct application.

Bargaining for power and information : an experimental and theoretical analysis of the interaction between institutions, externalities and adverse selection

Bargaining is the building block of many economic interactions, ranging from bilateral to multilateral encounters and from situations in which the actors are individuals to negotiations between firms or countries. In all these settings, economists have been intrigued for a long time by the fact that some projects, trades or agreements are not realized even though they are mutually beneficial. On the one hand, this has been explained by incomplete information. A firm may not be willing to offer a wage that is acceptable to a qualified worker, because it knows that there are also unqualified workers and cannot distinguish between the two types. This phenomenon is known as adverse selection. On the other hand, it has been argued that even with complete information, the presence of externalities may impede efficient outcomes. To see this, consider the example of climate change. If a subset of countries agrees to curb emissions, non-participant regions benefit from the signatories’ efforts without incurring costs. These free riding opportunities give rise to incentives to strategically improve ones bargaining power that work against the formation of a global agreement. This thesis is concerned with extending our understanding of both factors, adverse selection and externalities. The findings are based on empirical evidence from original laboratory experiments as well as game theoretic modeling. On a very general note, it is demonstrated that the institutions through which agents interact matter to a large extent. Insights are provided about which institutions we should expect to perform better than others, at least in terms of aggregate welfare. Chapters 1 and 2 focus on the problem of adverse selection. Effective operation of markets and other institutions often depends on good information transmission properties. In terms of the example introduced above, a firm is only willing to offer high wages if it receives enough positive signals about the worker’s quality during the application and wage bargaining process. In Chapter 1, it will be shown that repeated interaction coupled with time costs facilitates information transmission. By making the wage bargaining process costly for the worker, the firm is able to obtain more accurate information about the worker’s type. The cost could be pure time cost from delaying agreement or cost of effort arising from a multi-step interviewing process. In Chapter 2, I abstract from time cost and show that communication can play a similar role. The simple fact that a worker states to be of high quality may be informative. In Chapter 3, the focus is on a different source of inefficiency. Agents strive for bargaining power and thus may be motivated by incentives that are at odds with the socially efficient outcome. I have already mentioned the example of climate change. Other examples are coalitions within committees that are formed to secure voting power to block outcomes or groups that commit to different technological standards although a single standard would be optimal (e.g. the format war between HD and BlueRay). It will be shown that such inefficiencies are directly linked to the presence of externalities and a certain degree of irreversibility in actions. I now discuss the three articles in more detail. In Chapter 1, Olivier Bochet and I study a simple bilateral bargaining institution that eliminates trade failures arising from incomplete information. In this setting, a buyer makes offers to a seller in order to acquire a good. Whenever an offer is rejected by the seller, the buyer may submit a further offer. Bargaining is costly, because both parties suffer a (small) time cost after any rejection. The difficulties arise, because the good can be of low or high quality and the quality of the good is only known to the seller. Indeed, without the possibility to make repeated offers, it is too risky for the buyer to offer prices that allow for trade of high quality goods. When allowing for repeated offers, however, at equilibrium both types of goods trade with probability one. We provide an experimental test of these predictions. Buyers gather information about sellers using specific price offers and rates of trade are high, much as the model’s qualitative predictions. We also observe a persistent over-delay before trade occurs, and this mitigates efficiency substantially. Possible channels for over-delay are identified in the form of two behavioral assumptions missing from the standard model, loss aversion (buyers) and haggling (sellers), which reconcile the data with the theoretical predictions. Chapter 2 also studies adverse selection, but interaction between buyers and sellers now takes place within a market rather than isolated pairs. Remarkably, in a market it suffices to let agents communicate in a very simple manner to mitigate trade failures. The key insight is that better informed agents (sellers) are willing to truthfully reveal their private information, because by doing so they are able to reduce search frictions and attract more buyers. Behavior observed in the experimental sessions closely follows the theoretical predictions. As a consequence, costless and non-binding communication (cheap talk) significantly raises rates of trade and welfare. Previous experiments have documented that cheap talk alleviates inefficiencies due to asymmetric information. These findings are explained by pro-social preferences and lie aversion. I use appropriate control treatments to show that such consideration play only a minor role in our market. Instead, the experiment highlights the ability to organize markets as a new channel through which communication can facilitate trade in the presence of private information. In Chapter 3, I theoretically explore coalition formation via multilateral bargaining under complete information. The environment studied is extremely rich in the sense that the model allows for all kinds of externalities. This is achieved by using so-called partition functions, which pin down a coalitional worth for each possible coalition in each possible coalition structure. It is found that although binding agreements can be written, efficiency is not guaranteed, because the negotiation process is inherently non-cooperative. The prospects of cooperation are shown to crucially depend on i) the degree to which players can renegotiate and gradually build up agreements and ii) the absence of a certain type of externalities that can loosely be described as incentives to free ride. Moreover, the willingness to concede bargaining power is identified as a novel reason for gradualism. Another key contribution of the study is that it identifies a strong connection between the Core, one of the most important concepts in cooperative game theory, and the set of environments for which efficiency is attained even without renegotiation.

Building the capacity for learning and change through reflective conversation

Conversation is central to the process of organizational learning and change. Drawing on the notion of reflective conversation, we describe an action research project, "learning through listening" in Omega, a residential healthcare organization. In this project, service users, staff, members of management committees, trustees, managers, and central office staff participated in listening to each other and in working together towards building capacity for creating their own vision of how the organization could move into the future, according to its values and ethos. In doing so they developed ways of engaging in reflective conversation that enabled progress towards a strategic direction.

An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.

OBJECTIVES To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. STUDY DESIGN AND SETTING We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. RESULTS Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). CONCLUSION Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.

Planning and reporting of quality-of-life outcomes in cancer trials.

BACKGROUND Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.

The influence of ideological interest groups on congressional financial support of international family planning

The World Health Organization estimates there are about 585,000 maternal deaths each year, with 98% of the maternal deaths in developing countries. Access to family planning methods is one method to decrease maternal mortality and morbidity. ^ The U.S. was the leader in providing financial and technical assistance to developing countries to enable women to have this access. The election of Ronald Regan changed the course of U.S. support; abortion became a central factor in the political decision-making with regards to the financial support of international family planning. ^ One factor that may sway policy-makers' decisions is the influence of ideological interest groups, Political Action Committees funding of candidates in relation to votes on bills that impacted on financial support of international family planning and the amount spent by these groups on lobbyist was reviewed. Pro-choice funding of candidates was greater for the four of the fives votes supporting family planning. Pro-Choice lobbyist spending was $185,000 vs. $8,184,000 spent by Pro-Life ideological groups. ^

Maternal mortality in Texas 2001--2006

Background. Maternal mortality is often used as a measure of health and well being of women across the globe. Improved surveillance efforts at the state level can improve maternal mortality estimates and develop strategies to address the needs of maternal and child health populations. The aims of this study are (1) To provide better estimates of maternal mortality in Texas; (2) To better understand the origin, governance, function, sustainability and impact on policy and practice of maternal mortality review committees at the state level; and (3) To create a comprehensive implementation model for a statewide maternal mortality review committee.^ Methods. AIM I: Analyzed the enhanced surveillance of fetal death and live birth records linked to pregnancy-related and women of childbearing age (15-44 years) deaths records in Texas from 2001-2006. AIM II: Conduct semi-structured telephone interviews of key informants from states with active maternal mortality review committees. AIM III: Develop a comprehensive maternal mortality review committee implementation model for Texas from the results of AIMS I and II. ^ Results. AIM I: Enhanced surveillance methods identified almost 3.5 times more deaths that may be associated with pregnancy than standard methods. The leading cause of pregnancy-associated death from 2001-2006 among all causes, was accidents. The estimated pregnancy-associated mortality ratio for 2001-2006 was 31 maternal deaths per 100,000 live births. Enhanced surveillance confirmed a persistent race/ethnicity trend in maternal mortality. AIM II: Key informant interviews confirmed existing literature on maternal mortality review committees. Sustainability was maintained not only by the funding; but also by the dedication of committee members to conducting reviews and disseminating recommendations to improving quality of care and systems. All statewide committees examined preventability of deaths and provided recommendations to policymakers and stakeholders. Statewide committees also took the initiative to develop and implement programs to align healthcare systems and improve quality of care.^ Conclusion. The comprehensive implementation model for a statewide maternal mortality review committee has the potential to transform the knowledge learned from enhanced surveillance into a systematic effort to evaluate the circumstances surrounding a pregnancy-associated death; influencing policy and practice decisions addressing maternal mortality, women’s health and maternal and child health in Texas.^

AgEdS/Hort 465 Class: Horticulture Enterprise Management

The production of local fruit and vegetables is a rapidly expanding segment of Iowa agriculture. The new ISU AgEdS/Hort 465 class trains future growers in the management and operation of diversified horticultural enterprises on an Iowa farm situation. Management of the finances, production, and marketing is performed by the students. The course is structured as a business and is guided through decisions made by student committees (finance, operations, production, and marketing committees). Each committee investigates the feasibility of a desired enterprise before coming together to make a final decision. The course was offered for the first time in 2011.

Comités de bioética : su constitución y relevancia

Los Comités de Bioética son espacios de deliberación, interdisciplinarios, pluraIistas, críticos. Hay distintos tipos de comités: ética de la investigación, ética asistencial. ética de las organizaciones. Sus Integrantes, además de pertenecer a diferentes profesiones o actividades, deben tener una sólida formación en Bioética. Se promueve su constitución y funcionamiento en las instituciones para contribuir a resolver conflictos donde están en juego los valores morales de las personas.

La política criminal del legislador [Argentina, 2000-2009]

Investigación sobre la actividad legislativa que se encuentra en el trasfondo de las reformas al Código Penal argentino. El período analizado comprende los años 2000-2009. A través de proyectos de ley y dictámenes de comisiones de las cámaras del Congreso de la Nación se analiza el proceso de creación de las leyes, y las representaciones de violencia e inseguridad que tienen los legisladores. Así, pueden desentrañarse diversas categorías de violencia, derechos, bienes tutelados y el rol de la política criminal en un Estado de derecho

Nacimiento y evolución de los partidos políticos bonaerenses

El peso político de los hombres de la provincia de Buenos Aires dentro del concierto nacional, ha sido y es de significación. A partir de 1880, pese a las íntimas relaciones que tuvieron los partidos provinciales con sus respectivas conducciones nacionales, los primeros tomaron varias veces, caminos no siempre coincidentes con las segundas. Gran parte de los hombres que habrían de tener principal participación en el manejo político de la provincia y la nación en los últimos años del siglo XIX y primeros treinta del XX, se formaron, como así también su ideología y moral política, en el devenir de las tres presidencias posteriores a Pavón. El presente trabajo pretende estudiar básicamente las ideas y acciones de un grupo de aquellos que integraron el autonomismo y que habrían de descollar en los años posteriores a 1880.