Novel challenges of multi-society investigator-initiated studies: a paradigm shift for technique and technology evaluation

The introduction of innovative techniques and novel technologies into clinical practice is a challenge that confronts all aspects of healthcare delivery. Upheaval from shrinking research funding and declining healthcare reimbursements now forces patients, doctors, hospitals, payers, regulators, and even health systems into conflict as new therapies struggle to find a place in the therapeutic armamentarium. The escalating costs of healthcare force all parties to consider both the medical risks/benefits as well as the economic efficiency of proposed tools and therapies. We highlight these challenges by examining the process of initiating and conducting a “society-as-investigator” clinical trial to assess the safety of the natural orifice translumenal endoscopic surgery (NOTES) approach to cholecystectomy in the context of the issues that confront technology diffusion today.     

Diagnostik und Therapie des Harnblasenkarzinoms

Forty percent of patients with superficial bladder carcinoma progress towards muscle-invasive carcinoma despite initial therapy. Emergent technologies in the diagnostics and therapy of superficial bladder carcinoma including fluorescence cystoscopy are able to reduce recurrence and progression rates. Nevertheless to date no trial was able to show a benefit with regard to cancer-specific and overall survival using these new technologies. Lymph vessel invasion has been introduced as a new prognostic marker in muscle-invasive bladder carcinoma that can be easily incorporated into routine clinical practice. Furthermore adjuvant chemotherapy has been identified along with lymph node density as a statistically significant marker for survival in muscle-invasive bladder carcinoma which should be investigated in prospective clinical trials. In metastatic bladder carcinoma, vinflunine was approved as second-line chemotherapy for patients who failed cisplatin-based chemotherapy. This article critically reviews the emergent developments of the last 12-15 months and comments on their clinical efficacy for the treatment of bladder carcinoma.     

Health care technology assessment. Basic principles and clinical applications

Health care technology (defined as all drugs, devices, and medical and surgical procedures used in medical care as well as the organizational and supportive systems within which such care is provided) is widely regarded as an important driver of escalating health care spending in the United States. Many new health care technologies are adopted and used in clinical practice with little or no evidence that their use is associated with improved patient outcomes. Orthopaedic surgeons are facing increasing scrutiny from hospitals and payers regarding the adoption and use of new technology for the treatment of patients with musculoskeletal disease. Health care technology assessment is a growing field that is concerned with the multidisciplinary evaluation of clinical data on the basis of safety and efficacy as well as economic aspects of technology acquisition. Through an understanding of the relevant literature and the concepts of health care technology assessment, orthopaedic surgeons have an opportunity to participate in the assessment process and thus influence clinical and health policy decisions regarding the adoption and use of new and existing technologies in the field of orthopaedic surgery.     

In touch with robotics: neurosurgery for the future

The introduction of multiple front-end technologies during the past quarter century has generated an emerging futurism for the discipline of neurological surgery. Driven primarily by synergistic developments in science and engineering, neurosurgery has always managed to harness the potential of the latest technical developments. Robotics represents one such technology. Progress in development of this technology has resulted in new uses for robotic devices in our discipline, which are accompanied by new potential dangers and inherent risks. The recent surge in robot-assisted interventions in other disciplines suggests that this technology may be considered one of a spectrum of frontier technologies poised to fuel the development of neurosurgery and consolidate the era of minimalism. On a more practical level, if the introduction of robotics in neurosurgery proves beneficial, neurosurgeons will need to become facile with this technology and learn to harness its potential so that the best surgical results may be achieved in the least invasive manner. This article reviews the role of robotic technology in the context of neurosurgery.     

Healthcare technology and technology assessment

New technology is one of the primary drivers for increased healthcare costs in the United States. Both physician and industry play important roles in the development, adoption, utilization and choice of new technologies. The Federal Drug Administration regulates new drugs and new medical devices, but healthcare technology assessment remains limited. Healthcare technology assessment originated in federal agencies; today it is decentralized with increasing private sector efforts. Innovation is left to free market forces, including direct to consumer marketing and consumer choice. But to be fair to the consumer, he/she must have free knowledge of all the risks and benefits of a new technology in order to make an informed choice. Physicians, institutions and industry need to work together by providing proven, safe, clinically effective and cost effective new technologies, which require valid pre-market clinical trials and post-market continued surveillance with national and international registries allowing full transparency of new products to the consumer—the patient. No grant support. An erratum to this article can be found at     

How should new orthopaedic implants be introduced: an example and recommendations for best practice

Continued advancements in orthopaedics have led to the development of many new implants; many of these are being utilized in clinical practice with little or no evidence base for their safety or effectiveness. Highly publicized failures in orthopaedic technology have led to an increased awareness of this issue in both medical and non‐medical circles. In most cases, the significant harm caused to the public could have been avoided by the appropriately staged implementation of new implants. This review comments on the current literature regarding the optimal practice for the introduction of new orthopaedic technology. The authors’ experience with the failed ESKA Adapter Short‐stem/Modular Hip is described; the methodology used for its evaluation is used as a basis to discuss what was successful about the process and also give warning on what could be improved upon. The ideal practice requires new orthopaedic implants to be evaluated by high‐volume surgeons in specialist orthopaedic hospitals. These studies should include biomechanical studies, radiostereophotometric analysis, implant retrieval and outcome assessment. Results and complications should be reported early to the appropriate joint registry and regulatory body. Once a suitable evidence base has developed, the implant can be distributed into wider clinical practice or withdrawn. These recommendations aim to protect the patient and public from harm while allowing surgical innovation to still continue.     

Role of Systematic Reviews and Meta-analysis in Evidence-based Medicine

The overwhelming increase in the quantity of clinical evidence has led to detachment of the evidence and practice because new evidence can be integrated into clinical practice only after it has been critically appraised and synthesized on the basis of the existing evidence. Because many clinicians lack the skills and the time for such information processing, systematic reviews and meta-analyses, their quantitative counterparts, play an important role in health care. Well performed systematic reviews provide clinically relevant information for surgeons, abrogating the need to identify, read, and evaluate many individual studies. This article reviews the basic principles of meta-analysis, discusses its potential weaknesses such as heterogeneity and publication bias, and highlights special situations when dealing with surgical trials.     

Septic shock with multiorgan failure: from conventional apheresis to adsorption therapies

Septic shock is often associated with multiorgan failure, a life threatening clinical condition during which there is an imbalance in the proinflammatory and anti-inflammatory cytokines, chemokines, antigens, endotoxins, procoagulant, and anticoagulant factors and also resultant effects of therapeutic intervention like volume overload. Various extracorporeal therapies have shown some positive results as adjunctive therapeutic intervention to traditional antimicrobials in an effort to bring the inflammatory mediators to a homeostatic balance and to improve poor organ perfusion caused by hypotension and thrombosis in the microcirculation. This review focuses on current information on the use of therapeutic apheresis procedures as adjunctive therapy in such clinical situations as well as the exciting prospects for the near future. The sometimes disappointing results of early phase clinical studies may, in some cases, be related to the well known barriers to successful clinical trials in critically ill patients rather than to failure of the novel concept of adjunctive extracorporeal treatment of septic shock. It should be noted that some of the specialized apheresis technologies reviewed in this article are not yet available for clinical use in the United States as they are not yet approved for use by the US Food and Drug Administration.     

Neuropsychological technologies in rehabilitation

OBJECTIVE: To provide an introduction and a conceptual context for the articles presented in this special edition of the Journal of Head Trauma Rehabilitation on neuropsychological technologies. SUMMARY: Many clinical assessments in neuropsychology are metamorphosing from a psychometric search for a lesion to a functional image of the working brain. Behavioral probes increasingly employ technology to provide more ecologically valid stimuli to elicit diagnostically relevant responses. Intervention strategies include an expanding range of assistive devices and technologically based treatments. The advent of the microprocessor and discipline specific programming have allowed certain aspects of rehabilitation practice to incorporate these new assessment and intervention strategies. For example, the development of neuropsychological technologies has already lead to computer based prosthetics and orthotics, cognitive probes with millisecond accurate links to functional imaging, virtual reality managed ecological assessments, cognitive retraining, assistive devices, and online, and "real-time" database-driven evaluations. Emerging technologies offer the potential for personal, portable, everyday brain imaging and rehabilitation systems. Few psychologists, physiatrists, or allied health professionals are formally trained in technological development. What has emerged thus far is a collection of individual efforts that remain to be integrated into more comprehensive tools for the rehabilitation professions. The selective history of neuropsychological technologies presented here is meant to illustrate past difficulties in the emergence of this sub-specialty and point to new applications and technological integration that may prove fruitful. The convergence of neuroengineering, adaptive assessments, everyday neuroimaging, neuroinformatics, and educational neuroimaging, presage such future developments in neuropsychological technologies.     

Surgical clinical trials in melanoma

Over the past 30 years, several important surgery clinical trials examining the issues of excision margins, ELND, and regional therapy have given rise to the current practice guidelines for the care of melanoma patients. The development of the SLN selective lymphadenectomy concept and the increasing use of molecular staging techniques have presented new challenges in this field. Clinical trials have been initiated to address these latest issues. In the next decade, these trials should help guide the integration of the new technologies into the surgical management of melanoma.     

Robotic endovascular surgery: current and future practice

Minimally invasive techniques have been at the forefront of surgical progress, and the evolution of endovascular robotic technologies has seen a paradigm shift in the focus of future innovation. Endovascular robotic technology may help overcome many of the challenges associated with traditional endovascular techniques by enabling greater control, stability, and precision of target navigation and treatment, while simultaneously reducing operator learning curves and improving safety. Several robotic systems have been developed to perform a broad range of endovascular procedures, but none have been used at scale or widely in routine practice, and the evidence for their safety, effectiveness, and efficiency remains limited. High cost and device complexity, lack of haptic feedback, and limited integration and interoperability with existing equipment and devices are the principal technology, cost, and sustainability barriers to the scalability and widespread adoption in day-to-day practice. In order to fully realize its potential, future robotic innovation must ensure compatibility with a range of off-the-shelf equipment that can be tracked and exchanged quickly during a procedure and come together with developments in navigation, tracking, and imaging. Reducing cost and complexity and supporting sustainability of the technology is key. In parallel, new technologies must be evaluated by clear and transparent standardized outcomes and be accompanied by robust clinical training. Key to the successful future development and dissemination of robotic technology is open collaboration among industry, clinicians, and patients in order to fully understand and address current challenges and enable the technology to realize its full potential.     

An evidence-based approach to airway management: is there a role for clinical practice guidelines?

Complications arising out of airway management represent an important cause of anaesthesia-associated morbidity and mortality. Anaesthetic practice itself can lead to preventable harm, a particular example being persistent attempts at direct laryngoscopy, that results in delay in employing alternative strategies (or devices) when intubation is difficult. When patients are injured, expert review is called upon and often concludes that airway management provided by the anaesthetists was substandard. Many training programmes do not offer their trainees structured or organised teaching in airway management and many trainees probably enter practice with limited skills to deal with difficult airways. The literature on the management of the difficult airway in anaesthesia practice (especially as it relates to new technology and salvage strategies) is expanding rapidly. New technologies and practised response algorithms may be helpful in the management of the difficult airway, reducing the potential for adverse patient outcomes. Specialist societies and national interest groups can play an important role by critically reviewing and then applying the evidence base to generate clinical practice guidelines. The recommendations contained in such guidelines should be based on the most current evidence and they should be reviewed regularly for their content and continued relevance.     

Research and development at novel GmbH, Germany for prosthetics and paraplegics

Pressure distribution measurement offers an objective and quantifiable method of determining the loads applied to the human body during static and dynamic situations such as walking and the more demanding tasks associated with sporting activities. While there are various systems available on the market, the technology and developments offered by novel (novel.de) a company based in Munich, Germany are regarded as innovative. The intent of this article is to outline the development of novel's pressure measurement technology and explore how the pliance(?) system can assist in determining an optimal fit of a prosthesis in an athlete. The discussion also focuses on the introduction of a new Elastisens(?) technology of the novel sensor pads to enable analysis of very contoured surfaces. Key pressure parameters for determining optimal performance are also explored; however, clinicians and researchers are guided to acknowledging the need to direct and perform their analysis within context - in other words, the analysis must be hypothesis driven. Clinical relevance Pressure measurement analysis can play an important role in clinical assessment and various treatment modalities. As technology increases, so does the ability of pressure systems. Clinicians should be cognisant of evolving technology such as Elastisens(?), which can aid in prosthetic and wheelchair assessment.     

The role of surgeons in identifying emerging technologies for health technology assessment

Background

Health technology assessment (HTA) is a tool intended to help policy-makers decide which technologies to fund. However, given the proliferation of new technologies, it is not possible to undertake an HTA of each one before it becomes funded. Consequently, “horizon-scanning” processes have been developed to identify emerging technologies that are likely to have a substantial impact on clinical practice. Although the importance of physicians in the adoption of new technologies is well recognized, their role in horizon scanning in Canada has been limited. The purpose of this project was to pilot an approach to engage physicians, specifically surgeons, in provincial horizon-scanning activities.

Methods

We invited 18 surgeons from Alberta’s 2 medical schools to a horizon-scanning workshop to solicit their views on emerging technologies expected to impact surgical practice within the next 5 years and/or the importance of different attributes or characteristics of new technologies.

Results

Surgeons, regardless of specialty, identified developments designed to enhance existing minimally invasive surgical techniques, such as endoscopic, robotic and image-guided surgery. Several nonsurgical areas, including molecular genetics and nanotechnology, were also identified. Of the 13 technology attributes discussed, safety or risk, effectiveness and feasibility were rated as most important. Lastly, participating surgeons expressed an interest in becoming further involved in local HTA initiatives.

Conclusion

Surgeons, as adopters and users of health technologies, represent an important and accessible information source for identifying emerging technologies for HTA. A more formal, ongoing relationship between the government, HTA and surgeons may help to optimize the use of HTA resources.     

Estimating the economic value of emerging technologies in chronic wound therapy

Estimating the economic value of emerging technologies in clinical medicine presents a number of problems. New technologies may have a limited clinical history, few supportive peer‐reviewed publications, and only anecdotal evidence as they enter the market and seek clinician approval and reimbursement from payers. Although clinical efficacy/effectiveness research is a minimal starting point for making the case for adoption of a product, establishing a competitive cost‐effectiveness position against other products and establishing the case for economic value must be made as well when presenting to health plans or other payers. Economic valuation methods have been well developed in the business community. Reviewed here are the components of a well‐crafted case for the economic value of a product in general and in the wound industry specifically, in a multidomain approach to demonstrate values using demographic, clinical, financial, operational, and intangible assessments.     

Congress Presidential Address: 5th WAA Congress Therapeutic Artificial Organs, 10 Years After

Abstract: In 1983, more than 10 years ago, the concept of therapeutic artificial organs was proposed by this author. Currently developments of various types of immunomod-ulation technologies are well established, and therapeutic artificial organs for the treatment of autoimmunodiseases have become a well-accepted concept. It is this author's opinion that if we utilize apheresis technologies properly we should be able to prevent the aging process of mankind. Physical youth, and perhaps mental youth, can be achieved by apheresis technologies. However, in order to maintain youth and enjoy a high quality of life, it is essential to maintain a strong will to live. In this paper a new type of an artificial organ is proposed. This antiaging artificial organ is named "Juzo," the organ for a longer life, in Japanese, by this author.     

State of the Art of Lipid Apheresis

Abstract: Currently, 5 different lipid apheresis procedures are available for routine clinical treatment of hy–percholesterolemic patients. Unselective plasma exchange is a technically simple extracorporeal circuit, but albumin substitution fluid must be used and there is no high–density lipoprotein (HDL) recovery. Semiselective double filtration with improved size selectivity because of a small–pore secondary filter combines good elimination of low–density lipoprotein (LDL), lipoprotein (a) (Lp[a]), and fibrinogen with adequate HDL recovery; modifications such as thermofiltration, predilution/backflush, or pulsatile flow have been proposed for the improvement of this system. Three highly selective procedures are basedon immunologic or electrostatic interactions: immunoad–sorption using anti–low–density lipoprotein (LDL) antibodies, chemoadsorption onto dextran sulfate, and hep–arin–induced LDL precipitation (HELP) apheresis. The features of each system are discussed critically. Lastly, two new developments, Lp(a) immunoadsorption and LDL hemoperfusion using a polyacrylate LDL adsorber compatible with whole blood, are described     

New tools for classification and monitoring of autoimmune diseases

Rheumatologists see patients with a range of autoimmune diseases. Phenotyping these diseases for diagnosis, prognosis and selection of therapies is an ever increasing problem. Advances in multiplexed assay technology at the gene, protein, and cellular level have enabled the identification of 'actionable biomarkers'; that is, biological metrics that can inform clinical practice. Not only will such biomarkers yield insight into the development, remission, and exacerbation of a disease, they will undoubtedly improve diagnostic sensitivity and accuracy of classification, and ultimately guide treatment. This Review provides an introduction to these powerful technologies that could promote the identification of actionable biomarkers, including mass cytometry, protein arrays, and immunoglobulin and T-cell receptor high-throughput sequencing. In our opinion, these technologies should become part of routine clinical practice for the management of autoimmune diseases. The use of analytical tools to deconvolve the data obtained from use of these technologies is also presented here. These analyses are revealing a more comprehensive and interconnected view of the immune system than ever before and should have an important role in directing future treatment approaches for autoimmune diseases.     

The role of bone graft and alternatives in unstable distal radius fracture treatment

The increased prevalence of unstable fractures of the distal radius has stimulated the development of new technologies and new surgical techniques for treating these complex injuries. New developments also contribute to the expectation that orthopedic surgeons should be able to treat the fractured distal radius more successfully by achieving early stability, early function, and better outcomes. The continuous introduction of commercial bone graft substitutes and graft extenders has provided a large array of implantable materials. Rigorous comparison of the commercially available bone graft substitutes is difficult not only because of their diversity but also because uniformly accepted preclinical assays and comparable clinical studies have not been performed. Despite the lack of complete data, however, available data and collective experience suggest that bone graft substitutes can provide improved treatment methods and outcomes.