Previous studies have documented strategies to promote off-label use of drugs using journal publications and other means. Few studies have presented internal company communications that discussed financial reasons for manipulating the scholarly record related to off-label indications. The objective of this study was to build on previous studies to illustrate implementation of a publication strategy by the drug manufacturer for four off-label uses of gabapentin (Neurontin, Pfizer, Inc.): migraine prophylaxis, treatment of bipolar disorders, neuropathic pain, and nociceptive pain.
BACKGROUND: Tinnitus is the perception of a sound in the absence of an objective physical source. Up to now, there is no generally accepted view how these phantom sounds come about, and also no efficient treatment. Patients are turning to complementary or alternative medical therapies, such as acupuncture. Based on the theory of traditional Chinese medicine, acupoints located on both the adjacent and distal area of the disease can be needled to treat disease. Furthermore, the way of combining acupoints is for strengthening the curative effect. We aim to evaluate the efficacy of acupuncture at local points in combination with distal points in subjective tinnitus patients. METHOD: This trial is a randomized, single-blind, controlled study. A total of 112 participants will be randomly assigned to one of four treatment groups receiving acupuncture treatment for 4 weeks. The primary outcome measure is subjective tinnitus loudness and annoyance perception, which is graded using the Visual Analogue Scale (VAS). The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. DISCUSSION: Completion of this trial will help to identify whether acupuncture at local acupoints in combination with distal acupoints may be more effective than needling points separately.Trial registrationInternational Standard Randomized Controlled Trial Number Register: ISRCTN29230777.
Small incision lenticule extraction or SMILE is a novel form of ‘flapless’ corneal refractive surgery that was adapted from refractive lenticule extraction (ReLEx). SMILE uses only one femtosecond laser to complete the refractive surgery, potentially reducing surgical time, side effects, and cost. If successful, SMILE could potentially replace the current, widely practiced laser in-situ keratomileusis or LASIK. The aim of this study is to evaluate whether SMILE is non-inferior to LASIK in terms of refractive outcomes at 3 months post-operatively.
Intellectual property is associated with the creative work needed to design clinical trials. Two approaches have developed to protect the intellectual property associated with multicentre trial protocols prior to site initiation.The ‘open access’ approach involves publishing the protocol, permitting easy access to the complete protocol. The main advantages of the open access approach are that the protocol is freely available to all stakeholders, permitting them to discuss the protocol widely with colleagues, assess the quality and rigour of the protocol, determine the feasibility of conducting the trial at their centre, and after trial completion, to evaluate the reported findings based on a full understanding of the protocol. The main potential disadvantage of this approach is the potential for plagiarism; however if that occurred, it should be easy to identify because of the open access to the original trial protocol, as well as ensure that appropriate sanctions are used to deal with plagiarism.The ‘restricted access’ approach involves the use of non-disclosure agreements, legal documents that must be signed between the trial lead centre and collaborative sites. Potential sites must guarantee they will not disclose any details of the study before they are permitted to access the protocol. The main advantages of the restricted access approach are for the lead institution and nominated principal investigator, who protect their intellectual property associated with the trial. The main disadvantages are that ownership of the protocol and intellectual property is assigned to the lead institution; defining who ‘needs to know’ about the study protocol is difficult; and the use of non-disclosure agreements involves review by lawyers and institutional representatives at each site before access is permitted to the protocol, significantly delaying study implementation and adding substantial indirect costs to research institutes. This extra step may discourage sites from joining a trial.It is possible that the restricted access approach may contribute to the failure of well-designed trials without any significant benefit in protecting intellectual property. Funding agencies should formalize rules around open versus restricted access to the study protocol just as they have around open access to results.
BACKGROUND: Social anxiety disorder (SAD) is one of the most common anxiety disorders and is associated with marked impairments. However, a small proportion of individuals with SAD seek and receive treatment. Internet-administrated cognitive behavior therapy (iCBT) has been found to be an effective treatment for SAD. This trial will be the first Internet-delivered guided self-help intervention for SAD in Romania. METHODS: Participants with social anxiety disorder (N = 96) will be recruited via newspapers, online banners and Facebook. Participants will be randomized to either: a) an active treatment, or b) a waiting list control group.The treatment will have a guided iCBT format and will last for nine weeks. Self-report questionnaires on social phobia, anxiety, depression, treatment credibility and irrational thinking will be used. All assessments will be collected pre, post and at follow-up (six months after intervention). Liebowitz Social Anxiety Scale – Self-Report version (LSAS-SR) will be the primary outcome measure and will be administrated on a weekly basis in both conditions. DISCUSSION: The present randomized controlled trial investigates the efficacy of an Internet-administered intervention in reducing social anxiety symptoms in a culture where this form of treatment has not been tested. This trial will add to the body of knowledge on the efficacy of iCBT, and the results might lead to an increase of the accessibility of evidence-based psychological treatment in Romania.Trial registrationClinicalTrials.gov: NCT01557894.
BACKGROUND: Hypertension is a risk factor for cardiovascular disease, and the prevalence of hypertension tends to increase with age. Current treatments for hypertension have adverse side effects and poor adherence. The purpose of this study is to evaluate the effects of moxibustion on blood pressure in individuals with pre- or stage I hypertension.Methods/designForty-five subjects with pre- or stage I hypertension will be randomized into three groups: treatment group A (2 times/week), treatment group B (3 times/week), and the control group (non-treated group). The inclusion criteria will be as follows: (1) aged between 19 and 65 years; (2) prehypertension or stage I hypertension (JNC 7, Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure); (3) the participants are volunteers and written consent obtained.The participants in the treatment group A will undergo indirect moxibustion 2 times per week for 4 weeks, and the participants in the treatment group B will undergo indirect moxibustion 3 times per week for 4 weeks. The participants in the control group (non-treated group) will maintain their current lifestyle, including diet and exercise. The use of antihypertensive medication is not permitted. The primary endpoint will be a change in patient blood pressure. The secondary endpoints will be the body mass index, lipid profile, EuroQol and Heart Rate Variability. The data will be analyzed with the Student’s t-test and analysis of variance (ANOVA) (p < 0.05). DISCUSSION: The results of this study will help to establish the optimal approach for the care of adults with pre- or stage I hypertension.Trial registrationClinical Research Information Service KCT0000469.
BACKGROUND: Iliac artery atherosclerotic disease may cause intermittent claudication and critical limb ischemia. It can lead to serious complications such as infection, amputation and even death. Revascularization relieves symptoms and prevents these complications. Historically, open surgical repair, in the form of endarterectomy or bypass, was used. Over the last decade, endovascular repair has become the first choice of treatment for iliac arterial occlusive disease. No definitive consensus has emerged about the best endovascular strategy and which type of stent, if any, to use. However, in more advanced disease, that is, long or multiple stenoses or occlusions, literature is most supportive of primary stenting with a balloon-expandable stent in the common iliac artery . Recently, a PTFE-covered balloon-expandable stent (Advanta V12, Atrium Medical Inc., Hudson, NH, USA) has been introduced for the iliac artery. Covering stents with PTFE has been shown to lead to less neo-intimal hyperplasia and this might lower restenosis rates [2-4]. However, only one RCT, of mediocre quality has been published on this stent in the common iliac artery [5,6]. Our hypothesis is that covered balloon-expandable stents lead to better results when compared to uncovered balloon-expandable stents. METHODS: This is a prospective, randomized, controlled, double-blind, multi-center trial. The study population consists of human volunteers aged over 18 years, with symptomatic advanced atherosclerotic disease of the common iliac artery, defined as stenoses longer than 3 cm and occlusions. A total of 174 patients will be included.The control group will undergo endovascular dilatation or revascularization of the common iliac artery, followed by placement of one or more uncovered balloon-expandable stents. The study group will undergo the same treatment, however one or more PTFE-covered balloon-expandable stents will be placed. When necessary, the aorta, external iliac artery, common femoral artery, superficial femoral artery and deep femoral artery will be treated, using the standard treatment.The primary endpoint is absence of binary restenosis rate. Secondary endpoints are reocclusion rate, target-lesion revascularization rate, clinical success, procedural success, hemodynamic success, major amputation rate, complication rate and mortality rate. Main study parameters are age, gender, relevant co-morbidity, and several patient, disease and procedure-related parameters.Trial registrationDutch Trial Register, NTR3381.
BACKGROUND: Surgical conditions in laparoscopic surgery are largely determined by the depth of neuromuscular relaxation. Especially in procedures that are confined to a narrow working field, such as retroperitoneal laparoscopic surgery, deep neuromuscular relaxation may be beneficial. Until recently, though, deep neuromuscular block (NMB) came at the expense of a variety of issues that conflicted with its use. However, with the introduction of sugammadex, rapid reversal of a deep NMB is feasible. In the current protocol, the association between the depth of NMB and rating of surgical conditions by the surgeon and anesthesiologist is studied.Methods/design: This is a single-center, prospective, randomized, blinded, parallel group and controlled trial. Eligible patients are randomly assigned to one of two groups: (1) deep NMB (post-tetanic count, one or two twitches; n = 12) and (2) moderate NMB (train-of-four, 1 to 2 twitches, n = 12) by administration of high-dose rocuronium in Group 1 and a combination of atracurium and mivacurium in Group 2. The NMB in Group 1 is reversed by 4 mg/kg sugammadex; the NMB in Group 2 by 1 mg neostigmine and 0.5 mg atropine. Patients are eligible if they are over 18 years, willing to sign the informed consent form, and are scheduled to undergo an elective laparoscopic renal procedure or laparoscopic prostatectomy. A single surgeon performs the surgeries and rates the surgical conditions on a five-point surgical rating scale (SRS) ranging from 1 (poor surgical conditions) to 5 (excellent surgical conditions). The intra-abdominal part of the surgeries is captured on video and a group of five anesthesiologists and ten surgical experts will rate the videos using the same SRS. The primary analysis will be an intention-to-treat analysis. Evaluation will include the association between the level of NMB and SRS, as obtained by the surgeon performing the procedure and the agreement between the scoring of the images by anesthesiologists and surgeons. DISCUSSION: We aim to show that under the right conditions the perceived opposing goals of surgeons and anesthesiologists (optimal surgical conditions vs. optimal postoperative conditions) may be met without compromise to either.Trial registration: ClinicalTrials.gov identifier NCT01631149.
We have been investigating an ecologically valid strategy-training approach to enable adults with executive dysfunction to attain everyday life goals. Here, we report the protocol of a randomized controlled trial of the effects of this training compared to conventional therapy in a sample of community-dwelling adults with acquired brain injury and/or stroke.Methods/design: We will recruit 100 community-dwelling survivors at least six months post-acquired brain injury or stroke who report executive dysfunction during a telephone interview, confirmed in pre-training testing. Following pre-training testing, participants will be randomized to the ecologically valid strategy training or conventional therapy and receive two one-hour sessions for eight weeks (maximum of 15 hours of therapy). Post-testing will occur immediately following the training and three months later. The primary outcome is self-reported change in performance on everyday life activities measured using the Canadian Occupational Performance Measure, a standardized, semi-structured interview. Secondary outcomes are objective measurement of performance change from videotapes of treatment session, Performance Quality Rating Scale; executive dysfunction symptoms, Behavioural Rating Inventory of Executive Function – Adult; participation in everyday life, Mayo-Portland Adaptability Inventory Participation Index; and ability to solve novel problems, Instrumental Activities of Daily Living Profile.
Clinical research should ultimately improve patient care. For this to be possible, trials must evaluate outcomes that genuinely reflect real-world settings and concerns. However, many trials continue to measure and report outcomes that fall short of this clear requirement. We highlight problems with trial outcomes that make evidence difficult or impossible to interpret and that undermine the translation of research into practice and policy. These complex issues include the use of surrogate, composite and subjective endpoints; a failure to take account of patients' perspectives when designing research outcomes; publication and other outcome reporting biases, including the under-reporting of adverse events; the reporting of relative measures at the expense of more informative absolute outcomes; misleading reporting; multiplicity of outcomes; and a lack of core outcome sets. Trial outcomes can be developed with patients in mind, however, and can be reported completely, transparently and competently. Clinicians, patients, researchers and those who pay for health services are entitled to demand reliable evidence demonstrating whether interventions improve patient-relevant clinical outcomes.