Osteoarthritis Trials Research Articles

Domains rated as important by patients with hand osteoarthritis.

No data exist on patient participation in the selection of core domains for clinical trials of hand osteoarthritis (HOA). We aim to explore HOA patients' perspectives in the relative importance of domains. Seven domains affecting patients' lives were derived from a prior qualitative study. We recruited consecutive patients with symptomatic HOA to rate on 11-point numeric rating scales for each domain, from 0 representing "not important at all" to 10 representing "most important", with consideration in two scenarios: (a) how important the domains are in affecting their current lives; and (b) how important the domains are when there are treatments for HOA (eg exercise or drugs). Forty-five patients (91% female; mean age±standard deviation 64.3±7.5years) with mild HOA symptoms were included. Of these, 31%-42% rated current impact of HOA in various domains as highly important. Seven domains with rated scores of ≥7/10 in importance were endorsed for clinical trials in the following order: pain and HOA symptoms (endorsed by 77.8% of patients), physical function (66.7%), ability to participate in social roles (64.4%), ability to participate in social activities (62.2%), work productivity (62.2%), emotional health (60%), and appearance of fingers (55.6%). The preliminary important domains as endorsed by patients with HOA for inclusion into clinical trials were explored. Apart from pain and physical function, further research is needed to refine other domains of impact, such as participation, emotional health and aesthetic concerns, as core domain sets for HOA.

Turmeric/curcumin

Curcumin is the primary curcuminoid present in the turmeric plant, Curcuma longa, and gives turmeric its orange-yellow color. The names “turmeric” and “curcumin” are often used interchangeably, especially for the spice used in cooking. Turmeric extracts and curcumin are used primarily for osteoarthritis (OA) and inflammatory conditions. They also may have activity in diabetes, obesity, and cardiovascular diseases. Curcumin has anti-inflammatory activity via inhibition of arachidonic acid, lipoxygenase, COX, nuclear factor-kappa B, tumor necrosis factor-alpha, and interleukins. In a study of knee OA, 30 mg of curcumin extract three times daily decreased COX-2 secretion into synovial fluid, similar to the effect of 25 mg of diclofenac three times daily. In another study of knee OA, serum levels of Coll2-1, a cartilage-specific biomarker, were significantly reduced. Clinical trials demonstrating benefit have used 1,000–1,500 mg per day in divided doses. The oral bioavailability of turmeric/curcumin may be low, so products that contain black pepper extracts or other compounds as absorption enhancers are preferred. The most common adverse effects are GI discomfort and nausea. Human studies have shown good tolerance even with higher dosages. Curcumin inhibits platelet aggregation in vitro and in vivo, so patients taking antithrombotic agents such as warfarin or clopidogrel should use this botanical cautiously. Multiple small studies have evaluated curcumin and related compounds for treatment of OA and rheumatoid arthritis (RA), alone or in combination with other natural products. Although some studies were placebo controlled, others compared curcumin with NSAIDs. An Iranian study of 40 participants with knee OA compared treatment with 1,500 mg of curcuminoids per day in three divided doses with placebo for 6 weeks. Treatment with curcuminoids resulted in greater improvements on standard OA assessment tools, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne’s pain functional index, and visual analogue scale (VAS), with few adverse effects. Pain and physical function also improved, but not stiffness. An Indian trial1Amalraj A. et al.J Med Food. 2017; 20: 1022-1030Crossref PubMed Scopus (62) Google Scholar randomized 36 participants with RA into three groups to receive 250 mg or 500 mg of curcumin or placebo twice daily for 90 days. The active treatment groups had significant improvement in their clinical symptoms at study end. Favorable changes in disease markers also occurred, including the erythrocyte sedimentation rate, C-reactive protein levels, and rheumatoid factor values. A 2018 Indian study2Karlapudi V. et al.J Med Food. 2018; 21: 511-520Crossref PubMed Scopus (9) Google Scholar of 105 patients with OA evaluated a combination curcumin product versus placebo in a 90-day trial that demonstrated improvements in pain, physical function, and quality of life. A noninferiority trial of 367 participants with OA compared 1,500 mg of curcumin extract daily to 1,200 mg of ibuprofen daily for 4 weeks. The WOMAC total, pain, stiffness, and function scores were similar between the curcumin and ibuprofen groups, with about two-thirds of participants rating themselves as “improved” on the global assessment. Curcumin-treated patients had less abdominal pain. An OA trial of 120 participants evaluated several natural products. Patients were randomized to receive 500 mg of curcumin extract, 750 mg of glucosamine sulfate, curcumin extract/glucosamine sulfate, or placebo twice daily for 42 days. The VAS pain scores were reduced from baseline, with the greatest reduction in the curcumin extract group. The WOMAC scores were also improved in the curcumin extract group. Improvements from baseline were noted with glucosamine, but less than those with curcumin. Evidence for curcumin/turmeric is promising given its safety, and it may be an option for patients with mild OA symptoms. Inform patients that the curcumin formulations used in studies may not be widely available. Products containing compounds such as black pepper extract are recommended and should be taken with meals with fats or oils to enhance absorption.

Osteoartrozda yeni tedavi yöntemleri

Osteoartroz (OA) en yaygın artrit şeklidir. OA'da klinik çalışmaların sunduğu birçok zorluğa rağmen, hastalık patogenezi, hastalık süreci ve ağrının tedavisinin yanı sıra altta yatan hastalığın tedavisinde birçok yeni farmakolojik tedaviler ve klinik araştırmalar vardır. Yeni farmakolojik ajanlar ile klinikte OA'da semptomların ve hastalık sürecinin iyileştirilmesine yönelik fırsatlar ufukta görünmektedir.

Comparison of gait, functional activities, and patient-reported outcome measures in patients with knee osteoarthritis and healthy adults using 3D motion analysis and activity monitoring: an exploratory case-control analysis.

ObjectiveTo examine functional performance differences using kinematic and kinetic analysis between participants with and without knee osteoarthritis (OA) to determine which outcomes best characterize persons with and without knee OA.MethodsParticipants with unilateral moderate knee OA (Kellgren–Lawrence grades 2 or 3) and controls without knee pain were matched for age, gender, and body mass index. Primary outcomes included temporal parameters, joint rotations and moments, and ground reaction forces assessed via 3D motion capture during walking and ascending/descending stairs. Secondary outcomes included timed functional activities (sit to stand; tying shoelaces), 48 hrs lower limb activity monitoring, and patient-reported outcome measures (Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, European Quality of Life–5 Dimensions).ResultsEight matched pairs were analyzed. Compared with controls, OA participants exhibited significant reductions in peak frontal hip and sagittal knee moments, and decreased peak anterior ground reaction force with the affected limb while walking. Ascending stairs, OA participants had slower speed, fewer strides per minute, longer cycle and stance times, and increased trunk range of motion (ROM) in assessments of both limbs; longer swing time and reduced ankle ROM in the affected limb; and increased knee frontal ROM in the unaffected limb. Descending stairs, OA participants had fewer strides per minute and decreased trunk transverse ROM in assessments of both limbs; increased knee frontal ROM in the affected limb; and longer strides, shorter stance and cycle times, increased trunk sagittal and decreased knee transverse ROMs in the unaffected limbs vs controls. Compared with controls, OA participants had slower walking cadence (120–130 vs 100–110 steps/min, respectively), took significantly longer on timed functional measures, and had significantly worse scores in patient-reported outcomes.ConclusionSeveral objectives and patient-reported measures examined in this study could potentially be considered as outcomes in pharmacologic or physical therapy OA trials.

A Novel Smartphone Application for "Smart" Knee Osteoarthritis Trials

A Novel Smartphone Application for "Smart" Knee Osteoarthritis Trials

Rescue Analgesic Medication Use by Patients Treated with Triamcinolone Acetonide Extended-Release for Knee Osteoarthritis Pain: Pooled Analysis of Three Phase 2/3 Randomized Clinical Trials.

IntroductionIn clinical trials for knee osteoarthritis (OAK), rescue medication is commonly provided to manage uncontrolled index-knee pain. The impact of treatment on rescue medication utilization provides important information on the robustness of analgesic effect. In randomized controlled OAK trials (NCT01487161, NCT02116972, NCT02357459), intra-articular (IA) triamcinolone acetonide extended-release (TA-ER) demonstrated substantial, prolonged analgesia versus saline-placebo and TA crystalline solution (TAcs) as assessed by patient-reported pain scales. This pooled analysis assessed the impact of TA-ER on rescue medication use.MethodsPatients (N = 798) with OAK (American College of Rheumatology criteria; Kellgren–Lawrence grade 2/3) and baseline average daily pain intensity score ≥ 5 to ≤ 9 (0–10 numeric rating scale) received a single IA injection of TA-ER (N = 324), saline-placebo (N = 262), or TAcs (N = 212). Acetaminophen/paracetamol tablets were provided to treat uncontrolled pain (knee or otherwise). Rescue medication consumption was monitored through a daily diary; pill counts were confirmed at the clinical site. Differences in rescue medication use were measured by least-squares mean (LSM) differences, number of rescue medication tablets used per day, and in area under the effect (AUE) curves of rescue medication tablets used per week.ResultsThe overall number of rescue medication tablets used per day through week 24 was significantly less (p ≤ 0.05) for TA-ER versus saline-placebo (LSM difference, − 0.43) and TAcs (− 0.24). Rescue medication use was significantly (p ≤ 0.05) lower following TA-ER versus saline-placebo across weeks 1–12 (AUEweeks1–12; LSM difference, − 24.5) and weeks 1–24 (AUEweeks1–24; − 51.6) and versus TAcs across weeks 1–12 (AUEweeks1–12; − 21.1).ConclusionsIn patients with painful OAK, reduced rescue medication use may be a potential benefit of TA-ER and further supports its analgesic efficacy. Additional research is needed to assess whether TA-ER impacts the use of other common oral analgesics (nonsteroidal anti-inflammatory drugs, opioids) for patients with OAK.FundingFlexion Therapeutics, Inc., Burlington, MA, USA.Plain Language SummaryPlain language summary available for this article.

152 The OMERACT-OARSI core domain set for measurement in clinical trials of hip and/or knee osteoarthritis

152 The OMERACT-OARSI core domain set for measurement in clinical trials of hip and/or knee osteoarthritis

Outcome Domains, Outcome Measures, and Characteristics of Randomized Controlled Trials Testing Nonsurgical Interventions for Osteoarthritis.

Core outcome set (COS) is the minimum set of outcome domains that should be measured and reported in clinical trials. We analyzed outcome domains, prevalence of use of COS published by Outcome Measures in Rheumatology (OMERACT) initiative, outcome measures for outcome domains recommended by OMERACT COS, duration and size of randomized controlled trials (RCT) testing nonsurgical interventions for osteoarthritis (OA). We searched PubMed and analyzed RCT about nonsurgical interventions for OA published from June 2012 to June 2017. We extracted data about trial type, use of OMERACT COS, efficacy outcome domains, safety outcome domains, outcome measures used for COS assessment, duration, and sample size. Among 334 analyzed trials, complete OMERACT-recommended COS was used by 14% of trials. Higher median prevalence of using OMERACT COS was found in trials explicitly described as phase III, and trials of pharmacological interventions with followup ≥ 1 year, but both with wide range of COS usage. Trialists used numerous different outcome measures for analyzing core outcome domains: 50 different outcome measures for pain, 74 for physical function, 9 for patient's global assessment, and 5 for imaging. Suboptimal use of recommended COS and heterogeneity of outcome measures is reducing quality and comparability of OA trials and hinders conclusions about efficacy and comparative efficacy of nonsurgical interventions. Interventions for improving study design of trials in this field would be beneficial.

Uptake of the OMERACT-OARSI Hip and Knee Osteoarthritis Core Outcome Set: Review of Randomized Controlled Trials from 1997 to 2017.

To assess the uptake of the OMERACT-OARSI (Outcome Measures in Rheumatology- Osteoarthritis Research Society International) core outcome set (COS) domains in hip and/or knee osteoarthritis (OA) trials. There were 382 trials of hip and/or knee OA identified from the ClinicalTrial.gov registry from 1997 to 2017. Frequency of COS adoption was assessed by year and per 5-yearly phases. COS adoption decreased from 61% between 1997 and 2001 to 38% between 2012 and 2016. Pain (95%) and physical function (86%) were most consistently adopted. Patient's global assessment (48%) was the principal missing domain. Limited adoption of the COS domains indicates that further consideration to improve uptake is required.

The Role of Gene Therapy in Cartilage Repair.

The key principle of gene delivery to articulations by direct intra-articular injection is to release complementary DNA (cDNA)-encoding medical products that will lead to maintained, endogenous production of the gene products within the articulation. In fact, this has been accomplished for both in vivo and ex vivo gene delivery, using several vectors, genes, and cells in some animal models. Some clinical trials for rheumatoid arthritis and osteoarthritis (OA) using retrovirus vectors for ex vivo gene delivery and adeno-associated virus (AAV) for in vivo delivery have been reported. AAV is of special attention because, contrary to other viral vectors, it can enter deep within joint cartilage and transduce chondrocytes in situ. This quality is of special significance in OA, in which modifications in chondrocyte metabolism are believed to be crucial to the pathophysiology of the disease. The clinical effectiveness of TissueGene-C (TG-C), a cell and gene therapy for OA consisting of nontransformed and transduced chondrocytes (3:1) retrovirally transduced to overexpress TGF-β1 has been reported in patients with knee OA. The most common complications of TG-C were peripheral edema (9%), arthralgia (8%), articular swelling (6%), and injection site pain (5%). TG-C was associated with relevant ameliorations in function and pain. Gene therapy appears to be a viable method for the management of articular cartilage defects and OA.

Assessment of the Feasibility of Objective Parameters as Primary End Points for Patients Affected by Knee Osteoarthritis: Protocol for a Pilot, Open Noncontrolled Trial (:SMILE:).

Osteoarthritis (OA) is a disabling condition that affects more than one-third of people older than 65 years. Currently, 80% of these patients report movement limitations, 20% are unable to perform major activities of daily living, and approximately 11% require personal care. In 2014, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommended, as the first step in the pharmacological treatment of knee osteoarthritis, a background therapy with chronic symptomatic slow-acting osteoarthritic drugs such as glucosamine sulfate, chondroitin sulfate, and hyaluronic acid. The latter has been extensively evaluated in clinical trials as intra-articular and oral administration. Recent reviews have shown that studies on oral hyaluronic acid generally measure symptoms using only subjective parameters, such as visual analog scales or quality of life questionnaires. As a result, objective measures are lacking, and data validity is generally impaired. The main goal of this pilot study with oral hyaluronic acid is to evaluate the feasibility of using objective tools as outcomes to evaluate improvements in knee mobility. We propose ultrasound and range of motion measurements with a goniometer that could objectively correlate changes in joint mobility with pain reduction, as assessed by the visual analog scale. The secondary objective is to collect data to estimate the time and budget for the main double-blind study randomized trial. These data may be quantitative (such as enrollment rate per month, number of screening failures, and new potential outcomes) and qualitative (such as site logistical issues, patient reluctance to enroll, and interpersonal difficulties for investigators). This open-label pilot and feasibility study is conducted in an orthopedic clinic (Timisoara, Romania). The study includes male and female participants, aged 50-70 years, who have been diagnosed with symptomatic knee OA and have experienced mild joint discomfort for at least 6 months. Eight patients must be enrolled and treated with Syalox 300 Plus (River Pharma) for 8 weeks. It is a dietary supplement containing high-molecular-weight hyaluronic acid, which has already been marketed in several European countries. Assessments are made at the baseline and final visits. Recruitment and treatment of the 8 patients began on February 15, 2018, and was completed on May 25, 2018. Data analysis was planned to be completed by the end of 2018. The study was funded in February 2019. We expect the results to be published in a peer-reviewed clinical journal in the last quarter of 2024. The data from this pilot study will be used to assess the feasibility of a future randomized clinical trial in OA. In particular, the planned outcomes (eg, ultrasound and range of motion), safety, and quantitative and qualitative data must be evaluated to estimate in advance the time and budget required for the future main study. Finally, the pilot study should provide preliminary information on the efficacy of the investigational product. ClinicalTrials.gov NCT03421054; https://clinicaltrials.gov/study/NCT03421054. RR1-10.2196/13642.

Novel Approach to Estimate Osteoarthritis Progression: Use of the Reliable Change Index in the Evaluation of Joint Space Loss.

Osteoarthritis-related changes in joint space measurements over time are small and sensitive to measurement error. The Reliable Change Index (RCI) determines whether the magnitude of change observed in an individual can be attributed to true change. This study aimed to examine the RCI as a novel approach to estimating osteoarthritis progression. Data were from 167 men and 392 women with knee osteoarthritis (diagnosed using the American College of Rheumatology criteria) randomized to the placebo arm of the 3-year Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA) and assessed annually. The RCI was used to determine whether the magnitude of change in joint space width (JSW) on radiographs between study years was likely to be true or due to measurement error. Between consecutive years, 57-69% of participants had an apparent decrease (change <0) in JSW, while 31-43% of participants had annual changes indicating improvement in JSW. The RCI identified JSW decreases in only 6.0% of patients between baseline and year 1, and in 4.5% of patients between the remaining study years. The apparent increases in JSW were almost eliminated between baseline and year 1, and between years 1 and 2 only 1.3% of patients had a significant increase, dropping to 0.9% between years 2 and 3. The RCI provides a method to identify change in JSW, removing many apparent changes that are likely to be due to measurement error. This method appears to be useful for assessing change in JSW from radiographs in clinical and research settings.

The OMERACT-OARSI Core Domain Set for Measurement in Clinical Trials of Hip and/or Knee Osteoarthritis.

To update the 1997 OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) core domain set for clinical trials in hip and/or knee osteoarthritis (OA). An initial review of the COMET database of core outcome sets (COS) was undertaken to identify all domains reported in previous COS including individuals with hip and/or knee OA. These were presented during 5 patient and health professionals/researcher meetings in 3 continents (Europe, Australasia, North America). A 3-round international Delphi survey was then undertaken among patients, healthcare professionals, researchers, and industry representatives to gain consensus on key domains to be included in a core domain set for hip and/or knee OA. Findings were presented and discussed in small groups at OMERACT 2018, where consensus was obtained in the final plenary. Four previous COS were identified. Using these, and the patient and health professionals/researcher meetings, 50 potential domains formed the Delphi survey. There were 426 individuals from 25 different countries who contributed to the Delphi exercise. OMERACT 2018 delegates (n = 129) voted on candidate domains. Six domains gained agreement as mandatory to be measured and reported in all hip and/or knee OA clinical trials: pain, physical function, quality of life, and patient's global assessment of the target joint, in addition to the mandated core domain of adverse events including mortality. Joint structure was agreed as mandatory in specific circumstances, i.e., depending on the intervention. The updated core domain set for hip and/or knee OA has been agreed upon. Work will commence to determine which outcome measurement instrument should be recommended to cover each core domain.

The TeMPO trial (treatment of meniscal tears in osteoarthritis): rationale and design features for a four arm randomized controlled clinical trial

BackgroundMeniscal tears often accompany knee osteoarthritis, a disabling condition affecting 14 million individuals in the United States. While several randomized controlled trials have compared physical therapy to surgery for individuals with knee pain, meniscal tear, and osteoarthritic changes (determined via radiographs or magnetic resonance imaging), no trial has evaluated the efficacy of physical therapy alone in these subjects.MethodsThe Treatment of Meniscal Tear in Osteoarthritis (TeMPO) Trial is a four-arm multi-center randomized controlled clinical trial designed to establish the comparative efficacy of two in-clinic physical therapy interventions (one focused on strengthening and one containing placebo) and two protocolized home exercise programs.DiscussionThe goal of this paper is to present the rationale behind TeMPO and describe the study design and implementation strategies, focusing on methodologic and clinical challenges.Trial registrationThe TeMPO Trial was first registered at clinicaltrials.gov with registration No. NCT03059004. on February 14, 2017.

Applicability of trials in rheumatoid arthritis and osteoarthritis: A systematic review and meta-analysis of trial populations showing adequate proportion of women, but underrepresentation of elderly people

ObjectivesTo evaluate whether elderly people and women are adequately represented in randomized controlled trials (RCT) in rheumatoid arthritis (RA) and osteoarthritis (OA). MethodsFour systematic searches in MEDLINE yielded RCT in RA and OA on any intervention published in 2016 and 2017 and population-based studies (PBS) in RA and OA published between 2013 and 2017. Random effects meta-analyses estimated the pooled proportion of elderly people (defined as being ≥ 65 years old), the mean age, its standard deviation (SD), and the proportion of women stratified by disease (RA and OA) and study type (RCT and PBS). Stratified estimates were subsequently compared. Results265 RCT comprising 51,240 participants and 53 PBS comprising 523,630 participants were included. In both RA and OA, RCT included lower proportions of elderly people than PBS: RA –0.18 (95% confidence interval –0.22 to –0.13); OA –0.20 (–0.30 to –0.09); had lower mean ages: RA –5.2 years (–6.8 to –3.5); OA –4.7 years (–7.5 to –2.0); and smaller SD: RA –1.9 years (–2.6 to –1.3); OA –2.7 years (–4.2 to –1.2); (all comparisons: p ≤ 0.001). Proportions of women were comparable in RCT compared to PBS in both RA and OA. ConclusionsWhile women are adequately represented in RA and OA trials, the elderly are underrepresented, probably limiting applicability of current evidence to this growing subgroup. It is urgent to improve the inclusion of elderly people in clinical trials and study age as a determinant for outcome.

Work-related outcomes in randomized, double blind, placebo-controlled trials in osteoarthritis \u2013 are they adequately reported in journal publications? A systematic review

BackgroundOsteoarthritis (OA) has a high prevalence in Western societies and can affect an individual’s life in a number of domains, including work. In our experience, treatment trials on OA, however, rarely report work-related outcomes. Here we conducted a systematic review to assess the reporting of work-related outcomes in randomized, double blind, placebo-controlled trials in OA. Our systematic review also compared two search strategies for identifying eligible publications, one where work-related terms were included in the database search string (A) and one where this was not the case and work-related outcomes were identified by searches of full text Portable Document Formats (PDFs) (B). Search strategy A would conventionally be used and would only identify publications where work-related terms were mentioned in the title or abstract. Search strategy B presents the innovation of full text PDF searching and would identify publications were work-related terms were reported in the full text, regardless of whether they are mentioned in the title and abstract or not. We hypothesize that search strategy B identifies more relevant publications than search strategy A.MethodsElectronic database searching was performed in Medline (Pubmed) from database inception to February 23, 2017 to identify peer-reviewed articles of randomized, double blind, placebo-controlled treatment trials in OA of the hand, hip, or knee, available as full-text PDFs. For search strategy A, search terms to identify work-related outcomes were included in the database search string, while search strategy B did not have these terms included in the database search string, but instead involved full text PDF searching. We included English language articles only and only those articles where searchable PDFs were available, to enable a comparison between search strategies A and B. Additionally, included studies also needed to report on pain intensity in relation to the work-related outcomes.ResultsSearch strategy A yielded 50 hits combined for hand, hip or knee OA that mentioned some work-related concept in the title or abstract; 12 articles had to be excluded because they were not available as searchable PDFs. Screening of the remaining 38 articles resulted in only two articles that satisfied our inclusion criteria. Search strategy B yielded 986 hits, out of which 201 articles were excluded because searchable full text PDFs were not available. PDF full text searching and further screening resulted in 10 articles that were considered eligible for our review.ConclusionsWork-related outcomes are rarely reported in journal publication on randomized, double blind, placebo-controlled trials of hand, hip or knee OA. Searching full text PDFs yields more eligible articles than searching titles and abstracts only.

Emerging Treatment Models in Rheumatology: Challenges for Osteoarthritis Trials.

At a time when advancing understanding of osteoarthritis (OA) has created opportunities for new treatments, development of treatments has remained considerably behind advances in other rheumatic diseases. We describe elements of trial design and measurements that have inhibited success and offer suggestions that may help break the log jam. Among the problems with trials that include pain as an outcome measure are reliance on a single, non-optimal pain outcome, overestimation of likely effects of treatments on pain, and failure to identify patient subgroups most likely to respond to specific treatments. With regard to the use of structure modification as an outcome measure, demonstrating structure modification is often highly challenging, even with the use of magnetic resonance imaging. Many OA patients have advanced disease that is unlikely to respond to treatments that prevent cartilage loss. Further, prevention of cartilage loss and reduction of pain correlate weakly at best, and in at least some patients, reduction in pain may actually increase joint damage, making it impossible to demonstrate dual treatment effects on structure and pain in such scenarios. For structure outcomes, treatment effects on pain-sensitive structures such as bone and synovium may be more achievable than preventing cartilage loss. We suggest that changes in trial design related to some of these issues may increase the chances that new exciting and effective OA treatments will become available.

An observational analysis of discontinuation and non-publication of osteoarthritis trials

Discontinuation and nonpublication are causes for concern in highly funded research areas of prevalent medical conditions. The aim of our study is to evaluate the rate of discontinuation and nonpublication in osteoarthritis randomized controlled clinical trials. We used the ClinicalTrials.gov advanced search using the keyword "osteoarthritis" for phase 3 or phase 4 clinical trials in adults. Two investigators then independently screened the search results by registered title, condition, study design, and completion date. We then performed a systematic search to determine the publication status of the study. Our final analysis included 273 studies. Our analysis of these studies included 243 (89%) completed and 30 (11%) discontinued trials. A total of 121,307 (92%) and 10,368 (8%) patients participated in completed and discontinued trials, respectively. Following our searches of PubMed, Embase, and Google Scholar, we identified 67 of the 243 (27.6%) studies as completed but having not reached publication in manuscript form. If discontinuation and non-publication rates in osteoarthritis trials continue to be sub-optimal, already scarce research resources will continue to be wasted. One possible explanation for the witnessed nonpublication that warrants further investigation is the issue of publication bias or selective reporting bias, two known problems that decrease research productivity and ethics.

Glucosamine and Chondroitin Sulfate: What Has Been Learned Since the Glucosamine/chondroitin Arthritis Intervention Trial.

Glucosamine and chondroitin sulfate, alone or in combination, are used worldwide by individuals suffering from osteoarthritis pain. They are by prescription in some countries but are available as over-the-counter dietary supplements in other countries, such as the United States. The inconclusive results of the National Institutes of Health-sponsored Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) did little to clarify the efficacy of these agents. However, some newer studies have provided a better perspective on the potential benefits that they can offer. Because the 2 in combination showed a significant level of efficacy in the moderate-to-severe knee osteoarthritis subgroup of the GAIT, this review examines the randomized, controlled trials published from that time to the present. The findings of these studies are mixed, owing in some cases to the high rate of placebo response added to by the ethical incorporation of rescue analgesics into protocols designed to evaluate the slow-acting, subtle effects of glucosamine and chondroitin sulfate in combination. The strong influence of the placebo effect and confounding of results by rescue analgesics point to the importance of objective measurement tools such as osteoarthritis biomarker panels in long-term glucosamine/chondroitin sulfate clinical trials with less reliance on the subjective measurement tools commonly used in osteoarthritis trials of pharmaceuticals. [Orthopedics. 2018; 41(4):200-207.].

The quality of reporting in randomized controlled trials of acupuncture for knee osteoarthritis: A cross-sectional survey

ObjectiveTo assess the reporting quality of acupuncture trials for knee osteoarthritis (KOA), and explore the factors associated with the reporting.MethodThree English and four Chinese databases were searched from inception to December 2016 for randomized control trials testing effects of acupuncture for knee osteoarthritis. We used the standard CONSORT (2010 version), CONSORT Extension for Non-Pharmacological Treatments, and STRICTA for measuring the quality of reporting. Using pre-specified study characteristics, we undertook regression analyses to examine factors associated with the reporting quality.ResultsA total of 318 RCT reports were included. For the standard CONSORT, ten items were substantially under-reported (reported in less than 5% of RCTs), including specification of important changes to methods after trial commencement (0.6%), description of any changes to trial outcomes (0.0%), implementation of interim analyses and stopping guidelines (0.6%), statement about why the trial ended or was stopped (1.6%), statement about the registration status (4.4%), accessibility of full trial protocol (4.7%), implementation of randomization (4.7%), description of the similarity of interventions (3.5%), conduct of ancillary analyses (3.8%) and presentation of methods for additional analyses (4.4%). Four of the STRICTA items were under-reported (reported in less than 10% of RCTs), including description of acupuncture style (8.5%), presentation of extent to which treatment varied (1.3%), statement of practitioner background (7.2%) and rationale for the control (9.1%). For CONSORT Extension, the reporting was poor across all items (reported in less than 10% of trials). Trials including authors with expertise in epidemiology or statistics, published in English, or enrolling patients from multiple centers were more likely to have better reporting.ConclusionsThe reporting in RCTs of acupuncture for KOA was generally poor. To improve the reporting quality, journals should encourage strict adherence to the reporting guidelines.