This thesis proposed two nonparametric statistical tests, based on the Kolmogorov-Smirnov distance and L2 mallows disatnce. To implement the proposed tests, nonparametric bootstrap method is employed to approximate the distributions of the test statistics to construct the corresponding bootstrap confidence interval procedures. Monte-Carlo simulations are performed to investigate the actual type I error of the proposed bootstrap procedures. It is found that the type I error of the bootstrap BC confidence interval procedure is close to the nominal level when censoring is not heavy and the boosttrap percentile confidence interval procedure works well when Kolmogorov-Smirnov distance is used to characterize the equivalence. When the data is heavily censored, the procedures based on the Kolmogorov-Smirnov distance have very conservative type I errors, while the procedures based on the Mallows distance are very liberal. / Thesis (Ph.D, Mathematics & Statistics) -- Queen's University, 2007-08-01 10:43:32.345

No description available.

Thesis (M.Tech.: Chiropractic)--Durban University of Technology, 2009 / Objective: The efficacy of manipulation as compared to placebo in the treatment of two groups of weight trainers with Acromioclavicular (AC) Joint Dysfunction. Methods: Twenty patients (n=20), using randomised sampling were allocated to two intervention groups. Patients in each group received four treatments each over a two-week period and assessed at initial, one week, two weeks and one month follow ups. Objective measures included Algometer and Inclinometer readings. Numerical Pain Rating Scales (NRS), Shoulder Rating Questionnaire (SRQ) and the Shoulder Pain and Disability Index (SPADI) measured subjective outcomes. Results: Manipulation demonstrated significant improvement in objective findings. Subjective outcomes did not show significant difference between the manipulation and placebo groups. Conclusion: Manipulation, when compared to placebo, can be considered as an effective treatment intervention for the treatment of AC joint dysfunction with particular reference to objective outcomes. Although, caution needs to be utilised in accepting this outcome due to limitations in sample size, subjective measure sensitivity and specificity as well as the stringency of the inclusion and exclusion criteria.

Dissertation submitted in partial compliance with the requirements for a Masters Degree in Technology: Chiropractic, Durban University of Technology, 2009. / Headaches are one of the most common clinical conditions in medicine, and 80% of these are tension-type headaches (TTH). TTH has a greater socioeconomic impact than any other type of headache due to its prevalence. Within the TTH category, episodic TTH are more prevalent than chronic TTH. The mainstay in the treatment of TTH are simple analgesics and NSAIDs. Unless contraindicated, NSAIDs are often the most effective treatment for ETTH. However patients suffering with TTH tend to relate their headaches to increased muscle stiffness in the neck and shoulders and thus the non-pharmacological treatment of ETTH could be directed at the associated musculoskeletal components of ETTH. It is therefore proposed that the Kinesio Taping® Method may have an effect in the treatment of the muscular component of ETTH. Method: This study was a prospective randomised clinical trial with two intervention groups (n=16) aimed at determining the relative effectiveness of a NSAID and the Kinesio Taping® Method in the treatment of ETTHs. The patients were treated at 5 consultations over a 3 week period. Feedback was obtained using the: NRS – 101, the CMCC Neck Disability Index and a Headache Diary. Results: The Headache Diary showed a reduction in the presence and number, mean duration and pain intensity of ETTH in both groups. These treatment effects were sustained after the cessation of treatment with the exception of mean pain intensity in the Kinesio Taping® Method group. The mean NRS score decreased in both groups but at a slightly faster rate in the Kinesio Taping® Method group. The CMCC showed an improvement in the functional ability of the patients in both groups. Conclusion: There seems to be no significant difference in the relative effectiveness of the treatment modalities. We can thus state that the overall short-term reduction in symptomatology supports the use of NSAIDs or Kinesio Taping® Method in the treatment of ETTH.

Neuropathic pain (NPP) is a chronic syndrome suffered by patients with multiple sclerosis (MS), for which there is no cure. Underlying cellular mechanisms involved in its pathogenesis are multifaceted, resulting in significant challenges in its management. In addition to its complex pathophysiology, the clinical management of MS-induced NPP is further complicated by the lack of clinical therapeutics trials specific to this population. The primary aim of the work underlying this thesis was to contribute to the evidence-based management of individuals with MS-induced NPP through the completion of two clinical therapeutics trials in this population. A secondary aim was to describe pain variability in this patient population through the development and validation of a pain variability algorithm tool. Resulting from this work, we demonstrated that nabilone – a synthetic oral cannabinoid – represents an effective, well-tolerated and novel treatment for MS-induced NPP. Additionally, we show that the SSRI paroxetine was poorly tolerated in our patient population, with a correspondingly high attrition rate. As a result, we were unable to determine any treatment effect in this trial due to insufficient recruitment due to drop-out. Lastly, we were able to define and describe pain instability in this cohort, noting that approximately 30% of individuals with MS-induced NPP experiencing highly variable daily pain. The results of these projects provide novel information for this patient population. Patients currently living with the daily burden of MS-induced NPP would benefit from additional trials ensuing from this, and other, research in order to initiate a momentum for much-needed clinical research in this complicated patient cohort.

The pharmaceutical industry is spending more and more on Research and Development (R&D) every year. In addition, these R&D costs are increasing at a faster rate than sales. In order to resolve this dilemma a significant increase in R&D productivity is required. One of the main contributions to these R&D costs is the acquisition of data during clinical trials. The most important objective of a clinical trial is the collection of high quality data. No matter how well a clinical trial is conducted, if the data quality is poor, a meaningful analysis is not possible. The data acquisition method therefore plays a significant role in the overall outcome of a clinical trial. In this study a Mobile Clinical Data Acquisition System (MCDAS) was developed for the electronic collection of high-quality Patient-Reported Outcome (PRO) data. The system consisted of a cellular phone based electronic Diary (eDiary) for capturing data, and a website for administering the collected data. The system was designed so that it could be implemented on any clinical trials, no matter what data was collected. The MCDAS was successfully implemented on two clinical trials. The study shows that electronically capturing clinical data improves the quality of data obtained, thereby reducing the time and costs associated with clinical trials. / Thesis (M.Ing. (Electrical Engineering))--North-West University, Potchefstroom Campus, 2007.

The pharmaceutical industry is spending more and more on Research and Development (R&D) every year. In addition, these R&D costs are increasing at a faster rate than sales. In order to resolve this dilemma a significant increase in R&D productivity is required. One of the main contributions to these R&D costs is the acquisition of data during clinical trials. The most important objective of a clinical trial is the collection of high quality data. No matter how well a clinical trial is conducted, if the data quality is poor, a meaningful analysis is not possible. The data acquisition method therefore plays a significant role in the overall outcome of a clinical trial. In this study a Mobile Clinical Data Acquisition System (MCDAS) was developed for the electronic collection of high-quality Patient-Reported Outcome (PRO) data. The system consisted of a cellular phone based electronic Diary (eDiary) for capturing data, and a website for administering the collected data. The system was designed so that it could be implemented on any clinical trials, no matter what data was collected. The MCDAS was successfully implemented on two clinical trials. The study shows that electronically capturing clinical data improves the quality of data obtained, thereby reducing the time and costs associated with clinical trials. / Thesis (M.Ing. (Electrical Engineering))--North-West University, Potchefstroom Campus, 2007.

Background: There are a plethora of potential statistical designs which can be used to evaluate efficacy of a novel cancer treatment in the phase II clinical trial setting. Unfortunately, there is no consensus as to which design one should prefer, nor even which definition of efficacy should be used and the primary endpoint conclusion can vary depending on which design is chosen. It would be useful if an all-encompassing methodology was possible which could evaluate all the different designs simultaneously and allow investigators an understanding of the trial results under the varying scenarios. Methods: Finite Markov chain imbedding is a method which can be used in the setting of phase II oncology clinical trials but never previously evaluated in this scenario. Simple variations to the transition matrix or end-state probability definitions can be performed which allow for evaluation of multiple designs and endpoints for a single trial. A computer program is written in R which allows for computation of p-values and conditional power, two common statistical measures used for evaluation of trial results. A simulation study is performed on data arising from an actual phase II clinical trial performed recently in which the study conclusion regarding the efficacy of the potential treatment was debatable. Results: Finite Markov chain imbedding is shown to be useful for evaluating phase II oncology clinical trial results. The R code written for evaluating the simulation study is demonstrated to be fast and useful for investigating different trial designs. Further detail regarding the clinical trial results are presented, including the potential prolongation of stable disease of the treatment, which is a potentially useful marker of efficacy for this cytostatic agent. Conclusions: This novel methodology may prove to be an useful investigative technique for the evaluation of phase II oncology clinical trial data. Future studies which have disputable conclusions might become less controversial with the aid of finite Markov chain imbedding and the possible multiple evaluations which is now viable. Better understanding of activity for a given treatment might expedite the drug development process or help distinguish active from inactive treatments

Neuropathic pain (NPP) is a chronic syndrome suffered by patients with multiple sclerosis (MS), for which there is no cure. Underlying cellular mechanisms involved in its pathogenesis are multifaceted, resulting in significant challenges in its management. In addition to its complex pathophysiology, the clinical management of MS-induced NPP is further complicated by the lack of clinical therapeutics trials specific to this population. The primary aim of the work underlying this thesis was to contribute to the evidence-based management of individuals with MS-induced NPP through the completion of two clinical therapeutics trials in this population. A secondary aim was to describe pain variability in this patient population through the development and validation of a pain variability algorithm tool. Resulting from this work, we demonstrated that nabilone – a synthetic oral cannabinoid – represents an effective, well-tolerated and novel treatment for MS-induced NPP. Additionally, we show that the SSRI paroxetine was poorly tolerated in our patient population, with a correspondingly high attrition rate. As a result, we were unable to determine any treatment effect in this trial due to insufficient recruitment due to drop-out. Lastly, we were able to define and describe pain instability in this cohort, noting that approximately 30% of individuals with MS-induced NPP experiencing highly variable daily pain. The results of these projects provide novel information for this patient population. Patients currently living with the daily burden of MS-induced NPP would benefit from additional trials ensuing from this, and other, research in order to initiate a momentum for much-needed clinical research in this complicated patient cohort.

Age-related macular degeneration (AMD) is the leading cause of Government-registered blindness in the elderly of the Western world and has two forms: wet and dry. No current AMD therapies are curative, and most are provided after retinal damage from the disease has already occurred (to preserve what is left of the retina). We have constructed a multi-factorial Phase II randomized, controlled clinical trial, titled: “Omega-3 docosahexaenoic acid(DHA) and eicosapentaenoic acid (EPA) nutritional supplementation to delay the progression of age-related macular degeneration (AMD): The OMEGAlberta Study”. Each day, participants in the experimental arm of this study will receive 600mg DHA and 1200mg EPA, plus Vitalux AREDS antioxidant formula. Based on the physicochemical properties of DHA, EPA, and Vitalux, our aim is to delay the 5-year incident rate of progression of intermediate dry AMD to wet AMD. Several tests will be performed, not only to quantify the incident rate of progression of AMD, but also to gain insight of the physiological mechanisms behind the supplements being provided. If the supplements are proven to delay AMD progression, this knowledge should be implemented by changes in health services and policy relating to public education and the treatment of AMD.