2) A major funding effort is needed for clinical research, preferably based on a competitive model and using a peer review process, with more emphasis given to ‘bottom up’ proposals for projects and programmes, rather than ‘top down’ directives. At present, the best approach may be a combination of funding efforts at regional/national and EU-wide levels. The efforts should be substantial with growth planned over at least a decade. Increased funding for IDCT is crucial, from both public and private sources. A comprehen- sive survey of tax regulations relating to donations to medical research in countries throughout Europe might be useful. Such an overview could be used as a lobbying tool in those countries where tax exemptions for donations to medical research are not as generous as in others. For clinicaltrials it is especially crucial to
Phase III clinicaltrials have been suggested to be designed in order to analyze the efficacy of new drug and its therapeutic effect in clinical practices. Phase III trials have been conducted randomly on large number of patients (300-3000 or more), having the target to achieve the definite assessment of the new drug, by comparison with the standard drug treatment. Also, due to their longer duration and size, the Phase III trials have been considered as the most expensive, time consuming and difficult to design and run. In phase III trials, the chronic diseases having a period of evalution related to the time period of the intervention can be used in practice. In common practice, some trials of Phase III are continued until the regulatory submission is pended at the appropriate regulatory agency.
Although the need for pan-European clinicaltrials addressing questions that do not interest the commercial sector has been recognised, very little has been done to support this type of research at a Europe-wide level, compared to the support given by the public sector in the USA, mainly through the National Institutes of Health (NIHs) and the Veterans’ Administration. The ESF survey carried out in 1999 (see below), showed that clinicaltrials in Europe are mainly funded on a national basis, and that the annual total investment is of the order of 180 million euros. A number of these trials would be much more valuable if organised on a larger scale across Europe and drawing on national funding from several countries. A reasonable percentage of current investment at the national level should be coordinated and devoted to such pan- European clinicaltrials.
Through mapping out the clinical trial pathway (Phase 1) and exploring resources that might facilitate PPI across this pathway (Phase 2) the CTRC have identified that nu- merous resources currently exist to support PPI in research or that were suitable for adaptation by the CTRC. We have also identified the need for additional tools that could be developed to address current gaps in the toolkit. These will either be devel- oped locally by the CTRC PPI working group or in collaboration with others involved in PPI in other trials units. The tools within the toolkit will be designed to facilitate meaningful involvement by promoting clear planning of PPI from the outset, by provid- ing tools that encourage a considered approach to involvement activities, and by pro- viding ‘off the shelf’ resources, available online, to support clinicaltrials, as researchers are sometimes required to develop trials at a fast pace. Phase 2 is ongoing and only pre- liminary findings have therefore been presented. It is anticipated that by disseminating this work while the toolkit is in development, we will facilitate the engagement of vari- ous stakeholders, including public contributors and other clinicaltrials units in the toolkit’s ongoing development, thereby improving its quality.
ALLHAT in Perspective Implications to Clinical Practice and Clinical Trials MOVING POINTS ALLHAT in Perspective Implications to Clinical Practice and Clinical Trials K Yusoff, FACC Faculty of Medicine[.]
In the design of clinicaltrials, one of the key components is to have an appropriate sample size such that the minimally clinical accepted efficacy is detected with small errors. Some of the methodology to determine sample size is discussed in the following chapter. Most of the designs regard each clinical trial individually even though the success or the failure of one may have an impact on subsequent trials. A new design for a series of trials is proposed in Chapter 5 so that the optimality of the whole of the project development is considered. Following on that, a series of sequential trials with sequential sampling is proposed in Chapter 6. Patients are recruited sequentially and observations from the patients are then used to support if the current trial should continue recruitment, stop and initiate another clinical trial or abandon the development programme. Treatments targeting the same population may be more similar and thus may be correlated. The design for a series of sequential trials is therefore extended by considering the correlation between treatments (Chapter 7).
The debate around disclosure and clinical trial data release will undoubtedly continue with various stakeholders including funders, academics, industry, publishers and regulators supporting the move towards greater transparency. The new EU clinical trial regulation  published on 27 th May 2014 supports this claim under section (67). The guideline states that trial data should be publically accessible and presented in an easily searchable format, with related data and documents (including trial protocol and CSR) linked together by the EU trial number. The BMJ also stated that it will no longer publish trials of drugs or devices where the authors do not commit to making the relevant anonymised patient level data available, this is due to be extended to all submitted clinicaltrials from the 1st of July. The EMA have now adopted the new policy making clinicaltrials data more accessible . Roche should also be commended for voluntarily submitting their data and allowing further access to their CSRs. Our research provides further empirical evidence supporting the potential value of the CSR.
Outcome reporting bias has received much attention. Many empirical studies evaluating the consistency con- cerning outcomes between the protocol or trial registry entry of randomized clinicaltrials (RCTs) and subsequent publications have demonstrated that outcome reporting bias is prevalent and favors statistically significant results [9-16]. A recent study focusing on RCTs of traditional Chinese medicine (TCM) showed discrepancies were identified in primary outcomes (29%) and safety report- ing (28%) when comparing registered records with their subsequent publications . However, the problem of outcome-reporting bias has not been systematically stud- ied among RCTs of acupuncture.
This factsheet aims to help you to understand more about clinicaltrials. It is an agreed view on this topic by medical experts. We hope that it answers some of your questions about clinicaltrials, including what a trial is, the different types of trials and what to expect if you are taking part in a trial. If you have any other questions or concerns, please ask your doctor or call the National Cancer Helpline on freefone 1800 200 700.
Regardless of the magnitude of brain-work and animal screening, a time is reached when the new therapy must be administered to the first patient. This is the beginning of a clinical trial. Every conscientious surgeon will admit that his own experience results in the adoption of more critical attitude towards clinical problems. This is an example of ongoing clinical research which improves the overall surgical care. Putting this attitude of mind under discipline is the foundation of clinicaltrials. To get maximum information from a trial, the results may be compared with an already established “gold standard”, (comparative trials). Comparative studies may be blind (when the patient does not know the treatment, or double blind (when even the observer does not know the treatment) to get away with any bias influencing the results.
An analysis of 114 multicentre trials funded by the National Institute of Health Research (NIHR) Health Technology Assessment (HTA) and UK Medical Research Council (MRC), STEPS , showed that 45% failed to reach 80% of the prespecified sample size. Less than one third of the trials recruited their original target number of participants within the time originally speci- fied, and around one third had to be extended in time and resources. One factor observed in trials that recruited successfully was that they had employed a dedicated trial manager (odds ratio: 3.80, 95% CI: 0.79 to 36.14; P = 0.087). The STEPS collaborators suggest that anyone undertaking trials should think about the different needs at different phases in the life of a trial and put greater emphasis on ‘conduct’ (the process of actually doing trials) . In addition, the MRC acknowl- edged that the failure of some trials can be due to prac- tical problems with trial management rather than scientific problems or problems with the trial design . Francis et al.  examined whether clinicaltrials could be considered from a business management perspective and proposed that the dimensions of running a success- ful trial includes ‘ marketing ’ , ‘ sales ’ and ‘ ongoing client management ’ . They recognised that in the recruitment stage of a randomised controlled trial (RCT), the most demanding activity is to establish and implement a range of effective management techniques which parallel those used to run a successful business.
not be overlooked. Of utmost relevance to the transla- tional investigator are the ethical, legal and social issues surrounding genomic sequencing. In a recent study con- ducted by Allen and Foulkes, 30 cancer genome sequen- cing studies were assessed to evaluate how these issues are being handled across different jurisdictions . While they found a high degree of similarity in how cancer researchers engaged in these studies were pro- tecting participant privacy, there were no consistent means across these studies for re-contacting partici- pants, or for returning results and facilitating participant withdrawal. There was a strong trend towards both using samples for additional, unspecified research and sharing data with other investigators. Given the unique nature of genomic sequencing research, individuals and groups engaging in NGS clinicaltrials may benefit from human subjects training in these specific areas. How- ever, it is apparent that better-defined consensus stan- dards are still needed both nationally and internationally to prepare the growing number of researchers in this field [43,44].
patient enrollment from developing countries. The shift re ﬂ ects increased patient recruitment in the United States and decreased recruitment in Latin America, the lead developing re- gion involved in pediatric trials. The decrease in Latin American participa- tion may be due partly to the small number of antibiotic trials in the cur- rent sample. In the earlier cohort, the region was principally involved in large trials on antibiotics. There was no sig- ni ﬁ cant change in EU participation in clinicaltrials with respect to study involvement, although there was a statistically signi ﬁ cant, albeit small, increase in patient enrollment. This is not surprising, because the EU pedi- atric legislation did not enter into force until 2007.
of these agents and full explanation of their mechanism of action and information available should be revised by independent experts and the TeGenero trial regulators should have asked for more data about TGN1412safety and untested mechanisms of action in human before the trials (St Clair 2008). On the other hand 9 of these recommendations focused on the design of the study and accurate calculation of the first in-man study dose, as mentioned before dose of TGN1412 was not estimated correctly, also the dosing interval as the ESG stated that 10 minutes interval between infusion was too short to monitor adverse effect related to the TGN1412 infusion(St Clair 2008).Finally the ESG stated that first in-human trails should be conducted by highly qualified and trained investigators and they suggested introducing national accreditation system for principal investigators involved in clinicaltrials, summary of these recommendations listed in table-5(St Clair 2008).
of different pharmacokinetic and pharmacodynamic profiles in children as compared with adults. 3e5 Differ- ences in drug metabolism between children and adults also lead to differences in susceptibility to adverse drug reactions. 6 Worryingly, adverse drug reactions have been shown to occur more frequently with off-label prescribed drugs. 7 The magnitude of this problem is exemplified by one source which estimates that almost one-quarter of all children in the USA used at least one prescription drug in the last month and that the total number of drugs used per 100 children in the USA over 2004 and 2005 was 338.4. 8 To accelerate progress towards improved availability and access to safe child-specific medicines for all children below 12 years of age, the ‘Make medicines child size’ campaign was launched by the WHO in 2007. 9 It has been a requirement of the International Committee of Medical Journal Editors since 2004 that all clinicaltrials be prospectively registered in a publicly available clinicaltrials registry in order to be considered for publication of trial results. 10 As of April 2011 the WHO International ClinicalTrials Registry Platform (ICTRP) offers a single point of access (the ICTRP Search Portal) to data from over 130 000 clinicaltrials made available by clinical trial registries around the world. 11 The importance of high-quality information on clinicaltrials recruiting children is increasingly being recognised. The Pan African ClinicalTrials Registry (a WHO Primary Registry to the ICTRP) has, for example, recently created a child strategy, 12 and the European Union has implemented legislation mandating that the EudraCT database of clinicaltrials ‘should include a European register of clinicaltrials of medicinal products for paediatric use’. 13 To improve access to information on clinicaltrials in children for healthcare workers, researchers, and patients and their parents, the ICTRP has developed a filter (referred to as the ClinicalTrials in Children or CTC filter) on the ICTRP Search Portal which makes it possible to search the portal for clinicaltrials in children with reasonable accuracy. 14
A clinical trial is a research study to answer specific questions about vaccines or new therapies or new ways of using known treatments. ClinicalTrials also called medical research and research studies] are used to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinicaltrials are the fastest and safest way to find treatments that work. Leads for clinicaltrials usually come from researchers. Once researchers test new therapies or procedures in the laboratory [animal studies] and get promising results, they begin planning Phase I clinicaltrials [in humans].New therapies are tested on people only after laboratory and animal studies show promising results. ClinicalTrials make it possible to apply the latest scientific and technological advances to patient care. When a new medical treatment is studied for the first time in humans, it is not known exactly how it will work. With any new treatment, there are possible risks as well as benefits.
Methods and Materials: In this randomised clinical trial, we prescribed the prophylactic oral antibiotic (Ciprofloxacin, 500 mg once daily) one day before performing the prostate needle biopsy, until two days after the procedure in 210 patients with 40-70-year-old age who were candidates for TRUS-guided prostate biopsy. The enrolled patients were randomly allocated to two equal groups (105 patients in each one). Systemic oral antibiotic and topical disinfection of the rectum by povidone-iodine 1% solution were applied for all patients, while direct intraprostatic injection of antibiotic (Amikacin, 1 ml into each prostate lobe) was performed just in one of the groups. All of the patients were followed for 30 days for the development of any symptoms of infection including fever, pelvic pain, and pyuria.
There are several limitations associated with this research. The human clinicaltrials presented herein were uncontrolled case series and were subject to associated bias influences. Sec- ond, long-term data with the KineSpring System are currently unavailable, and therefore the results presented herein should be considered preliminary. Lastly, the KineSpring System has very specific indications and contraindications for use, which limits the applications of this implant. Importantly, the KineSpring System is not intended for patients with lateral or patellofemoral knee OA. Additionally, the device is only intended to unload the knee joint during gait, but not during activities such as squatting or stair climbing. Prospective controlled clinicaltrials with larger sample sizes are warranted to elucidate further the effects of the KineSpring System. The GOAL study (Study of the KineSpring System Versus High Tibial Osteotomy Surgery for the Treatment of Medial Compartment Knee Osteoarthritis; NCT01610505) 41 is one
Discussion: The Finnish law makes an arbitrary distinction between medical research and other health research, and the European Union's directive for good clinicaltrials further differentiates drug trials. The starting point of current rules is that clinicaltrials are lesser in the interest of patients and society than routine health care. However, commercial interests are not considered unethical. The contrasting procedures in research and normal health care may tempt physicians to continue introducing innovations into practice by relying on unsystematic and uncontrolled observations. Tedious and bureaucratic rules may lead to the disappearance of trials initiated by researchers. Trying to accommodate the special legislative requirements for new drug trials into more complex interventions may result in poor designs with unreliable results and increased costs. Meanwhile, current legal requirements may undermine the morale of ethics committee members.
According to Kimmelman, social value can be assigned to clinicaltrials, but also to the information human ex- periments produce . In addition to assigning value to different objects, Kimmelman also distinguishes between different kinds of value, like progressive value (the value of a trial is seen as the likelihood it will progress to the next phase), translational value (the value of a trial is perceived to be wider than merely progression to the next phase, and also includes informing preclinical testing, other areas of research, or a change in the intervention), and humanitarian value of clinicaltrials (the value clinical research has because ‘it advances broader societal ends like improved healthcare’) . Casarett and colleagues distinguish two categories in their proposed term health value (the potential of a study to improve health): immediate health value and the future health value of a study . Examples of studies that have im- mediate health value are phase III clinicaltrials as they have the potential to improve health as soon as the drug has been proven effective and approved. Phase I trials, in contrast, have potential future health value as their value lies in their contribution to future research. Karlawish makes a similar distinction when he claims that research that will directly change clinical practice has clinical value, which is optional for a study, whereas scientific validity and value is necessary and sufficient . (In this paper we will use first-in-human and phase I studies interchangeably, although we are aware that first-in- human research consist of more than merely phase I trials.)