Assessing the reliability and credibility of industry science and scientists.

The chemical industry extensively researches and tests its products to implement product stewardship commitments and to ensure compliance with governmental requirements. In this commentary we argue that a wide variety of mechanisms enable policymakers and the public to assure themselves that studies performed or funded by industry are identified as such, meet high scientific standards, and are not suppressed when their findings are adverse to industry's interests. The more a given study follows these practices and standards, the more confidence one can place in it. No federal laws, rules, or policies express a presumption that scientific work should be ignored or given lesser weight because of the source of its funding. To the contrary, Congress has consistently mandated that agencies allow interested or affected parties to provide information to them and fairly consider that information. All participants in scientific review panels should disclose sources of potential biases and conflicts of interest. The former should be considered in seeking a balanced panel rather than being used as a basis for disqualification. Conflicts of interest generally do require disqualification, except where outweighed by the need for a person's services. Within these constraints, chemical industry scientists can serve important and legitimate functions on scientific advisory panels and should not be unjustifiably prevented from contributing to their work.

Workshop proceedings: managing conflict of interest in science. A little consensus and a lot of controversy.

There is no doubt that participants in the Conflict of Interest (COI) Workshop at the Society of Toxicology (SOT) 2005 Annual Meeting (New Orleans, 6-10 March 2005) engaged in a vigorous and useful exchange of diverse ideas and viewpoints. While there was consensus on the value and interest of this Workshop, there was less consensus and more controversy over many of the issues discussed during the Workshop, which included the distinction between bias and conflict, the success or failure of policies of disclosure, whether waivers should or should not be granted to conflicted individuals in order to seat a "balanced" committee with appropriate expertise, whether conflicted individuals retain the ability to recognize their own conflict, and more. The discussion left no doubt, however, that conflict of interest will remain an important and controversial issue in the scientific community for some time to come.

Enhancement of syndesmotic fusion rates in total ankle arthroplasty with the use of autologous platelet concentrate.

BACKGROUND: One of the challenges of total ankle arthroplasty continues to be achieving a solid distal fusion of the tibiofibular joint. Delayed union rates of 29% to 38% and the nonunion rates of 9% to 18% for syndesmotic fusion have been documented. The risk of tibial component migration has been reported to increase 8.5 times if a solid syndesmotic fusion is absent. Growth factors have been shown to accelerate bone healing and may enhance the fusion of the syndesmosis and, thereby, decrease the frequency of nonunion and subsequent tibial component migration. METHODS: An autologous platelet concentrate was used to increase the amount of growth factors at the site of the distal tibiofibular joint fusion in 20 total ankle arthroplasties. RESULTS: Our 6-month fusion rate was 100%. When compared to historical controls (6-month fusion rate of 62%) the difference was statistically significant (p < 0.0001). CONCLUSION: The improved rate of distal tibiofibular fusion may be attributable to the increased presence of growth factors provided by an autologous platelet concentrate.

The use of autologous concentrated growth factors to promote syndesmosis fusion in the Agility total ankle replacement. A preliminary study.

BACKGROUND: The Agility (DePuy, Warsaw, Indiana) total ankle replacement has been in use since 1984. One of the most common complications continues to be delayed union or nonunions of the distal tibiofibular syndesmosis. In the reported studies on the Agility ankle the delayed union and nonunion rate can be as high as 38%. METHODS: Since 1999, 114 Agility total ankle replacements were done at two centers in the United States without the use of autologous concentrated growth factors. Since July of 2001, 66 Agility ankles were implanted with Symphony (DePuy, Warsaw, Indiana) augmented bone grafting. The standard operative technique was followed in all the patients. Prospective data was collected on all patients. The standard ankle radiographs were taken preoperatively and postoperative at 8 weeks, 12 weeks, 16 weeks, 6 months, and yearly. CT scans were obtained at 6 months if fusion at the syndesmosis was questionable. The Graphpad Instat software (Graphpad Software Inc., San Diego, CA) was used for statistical analysis. The two-tailed unpaired t-test was used, and the value <0.05 was considered significant. RESULTS: There was no statistical difference in the demographic data for the two groups. In 114 ankle replacements without autologous concentrated growth factors 70 fused at 8 weeks (61%), 14 fused at 12 weeks (12%), 13 fused at 6 months (12%). There were 17 nonunions (15%); delayed unions (3 to 6 months) and nonunions, therefore, equaled 27%. The syndesmosis fused in 50 of the 66 ankle replacements (76%) that had autologous concentrated growth fractures at 8 weeks (76%); 12 fused at 3 months (18%), 2 fused at 6 months (3%), 2 had nonunions (3%). Delayed unions (3 to 6 months) and nonunions equaled 6%. There was a statistically significant improvement in the 8- and 12-week fusion rates, and a statistically significant reduction in delayed unions and nonunions. CONCLUSION: Autologous concentrated growth factors appear to make a significant positive difference in the syndesmosis union rate in total ankle replacements.

Data disclosure for chemical evaluations.

BACKGROUND: Public disclosure of scientific data used by the government to make regulatory decisions for chemicals is a practical step that can enhance public confidence in the scientific basis of such decisions. OBJECTIVES: We reviewed the U.S. Environmental Protection Agency's (EPA) current practices regarding disclosure of data underlying regulatory and policy decisions involving chemicals, including pesticides. We sought to identify additional opportunities for the U.S. EPA to disclose data and, more generally, to promote broad access to data it uses, regardless of origin. DISCUSSION: We recommend that when the U.S. EPA proposes a regulatory determination or other policy decision that relies on scientific research, it should provide sufficient underlying raw data and information about methods to enable reanalysis and attempts to independently reproduce the work, including the sensitivity of results to alternative analyses. This recommendation applies regardless of who conducted the work. If the U.S. EPA is unable to provide such transparency, it should state whether it had full access to all underlying data and methods. A timely version of submitted data cleared of information about confidential business matters and personal privacy should fully meet the standards of transparency described below, including public access sufficient for others to undertake an independent reanalysis. CONCLUSION: Reliable chemical evaluation is essential for protecting public health and the environment and for ensuring availability of useful chemicals under appropriate conditions. Permitting qualified researchers to endeavor to independently reproduce the analyses used in regulatory determinations of pesticides and other chemicals would increase confidence in the scientific basis of such determinations.

Accelerating the development of 21st-century toxicology: outcome of a Human Toxicology Project Consortium workshop.

The U.S. National Research Council (NRC) report on "Toxicity Testing in the 21st century" calls for a fundamental shift in the way that chemicals are tested for human health effects and evaluated in risk assessments. The new approach would move toward in vitro methods, typically using human cells in a high-throughput context. The in vitro methods would be designed to detect significant perturbations to "toxicity pathways," i.e., key biological pathways that, when sufficiently perturbed, lead to adverse health outcomes. To explore progress on the report's implementation, the Human Toxicology Project Consortium hosted a workshop on 9-10 November 2010 in Washington, DC. The Consortium is a coalition of several corporations, a research institute, and a non-governmental organization dedicated to accelerating the implementation of 21st-century Toxicology as aligned with the NRC vision. The goal of the workshop was to identify practical and scientific ways to accelerate implementation of the NRC vision. The workshop format consisted of plenary presentations, breakout group discussions, and concluding commentaries. The program faculty was drawn from industry, academia, government, and public interest organizations. Most presentations summarized ongoing efforts to modernize toxicology testing and approaches, each with some overlap with the NRC vision. In light of these efforts, the workshop identified recommendations for accelerating implementation of the NRC vision, including greater strategic coordination and planning across projects (facilitated by a steering group), the development of projects that test the proof of concept for implementation of the NRC vision, and greater outreach and communication across stakeholder communities.

Enhancing the credibility of decisions based on scientific conclusions: transparency is imperative.

Transparency and documentation of the decision process are at the core of a credible risk assessment and, in addition, are essential in the presentation of a weight of evidence (WoE)-based approach. Lack of confidence in the risk assessment process (as the basis for a risk management decision), beginning with evaluation of raw data and continuing through the risk decision process, is largely because of issues surrounding transparency. There is a critical need to implement greater transparency throughout the risk assessment process, and although doing so will not guarantee the correctness of the risk assessment or that all risk assessors come up with the same conclusions, it will provide essential information on how a particular conclusion or decision was made, thereby increasing confidence in the conclusions. Recognizing this issue, the International Life Sciences Institute Health and Environmental Sciences Institute convened a multisector committee tasked with discussing this issue and examining existing guidance and recommendations related to transparency in risk assessment. The committee concluded that transparency is inextricably linked to credibility: credibility of the data, credibility of the risk assessment process, and credibility of the resulting decision making. To increase this credibility, existing guidance concerning criteria elements of transparency related to the risk assessment process must be more widely disseminated and applied, and raw data for studies used in human health and environmental risk assessment must be more widely available. Finally, the decision-making process in risk management must be better documented and a guidance framework established for both the process itself and its communication to the public.