Assessing heterogeneity in relative treatment efficacy by age, sex and comorbidity.

Lead Investigator: David McAllister, University of Glasgow
Title of Proposal Research: Assessing heterogeneity in relative treatment efficacy by age, sex and comorbidity.
Vivli Data Request: 5483
Funding Source: This research is funded via Dr McAllister’s Wellcome Trust Fellowship Ref: 201492Z16Z
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Less than half of patients with a chronic condition have only a single disease. Most have multiple diseases – or multimorbidity. People with multimorbidity are less likely to receive recommended treatments; Partly because clinical practice guidelines, which make treatment recommendations, rarely provide specific treatment recommendations for people with multimorbidity.

This rarity reflects uncertainty as to whether standard treatment recommendations should apply to multimorbidity. Clinical trials usually resolve such uncertainties, but it is not feasible to conduct trials large enough to examine the most common patterns of multimorbidity, even for the most important treatments. Analysing data from large healthcare databases is a feasible alternative, but such analyses have in several cases led to inaccurate conclusions.

Therefore, individual clinicians have to estimate treatment effectiveness in people with multimorbidity unsupported by guidance or high quality evidence. There is therefore a need to develop novel methods, for determining treatment effectiveness in multimorbidity.
Evidence synthesis (ES), where modellers combine data from multiple sources, is a promising approach. Using ES, results from clinical trials may be combined with other data to estimate treatment effects for particular groups. However, ES has not yet been developed for the problem of multimorbidity and there are a number of additional challenges.

In a project funded by the Wellcome Trust we plan to develop and validate an approach to determine treatment effectiveness in people with multimorbidity. As part of that project we aim to determine whether and how, for different groups of related drug-classes, relative treatment effects differ according to the presence or absence of specific co-existing diseases.

We have identified 201 suitable trials. We will use these to ‘survey’ how treatment effects vary according to the presence of co-existing diseases for different types of drug and treatment outcome (eg blood pressure, mortality).

Rather than focusing on individual drugs we will summarise this variation for drug-classes and groupings of related drug classes. We will use statistical models similar to those outlined in the NICE Technical Support Documents for ES.

This work will improve the health of people with multimorbidity. If we find that there is very little variation, it will considerably simplify the challenge of determining treatment effectiveness in multimorbidity. If instead we discover substantial variation, this knowledge may be incorporated into ES, resulting in more robust valid estimates of treatment effectiveness.

Statistical Analysis Plan:

Rationale
The wider rationale for this research is given more fully in the lay summary section, but is outlined briefly below.
Multimorbidity is common and increasing. Less than half of patients with a chronic condition have only a single disease. As multimorbidity is commoner in older people, it is likely to become more prevalent as the population ages, making the provision of optimal care increasingly complex.
Multimorbid patients are less likely than those with single diseases to receive recommended drugs, even where there are no specific contraindications. This difference may represent under treatment or may have arisen from uncertainty among clinicians as to the applicability of clinical guidelines, which rarely provide specific advice on managing multimorbidity. Where multimorbidity alters the (baseline) natural history of diseases, the effects of treatment are likely to differ. For example, while there is strong evidence that the benefits of dual antiplatelet therapy (DAPT) following myocardial infarction (versus a single antiplatelet) outweigh the risks, this may not be true for patients with comorbid chronic obstructive pulmonary disease (COPD). Cardiovascular mortality is commoner in COPD than the general population, favouring DAPT. However, non-cardiovascular mortality is also higher, favouring single-antiplatelet therapy because of competing risks. Glucose and intensive risk factor control in diabetes and anticoagulant use in atrial fibrillation provide similar examples, where the net overall treatment benefits are uncertain for multimorbid patients.
Neither clinical trials nor observational studies fully address this problem. Trialists do not report results stratified by combinations of important comorbidities. Nor is it feasible to conduct trials sufficiently large to allow such comparisons for all indications. Administrative healthcare databases are sufficiently large. However, while estimates of treatment effectiveness obtained from observational studies are generally comparable to those from clinical trials, they have in several cases led to inaccurate conclusions.
The complexity and prevalence of multimorbidity is increasing, hence the question of how treatment effectiveness differs for people with comorbidity is becoming increasingly important.
Currently, individual clinicians must estimate treatment effectiveness in older, sicker people with multimorbidity unsupported by guidance or high-quality evidence. There is therefore a need to find alternative approaches to produce estimates of net overall treatment benefits for patients with multimorbidity.
In a Wellcome Trust funded project, we intend to develop and validate an approach based around Bayesian Evidence Synthesis to estimate treatment effectiveness in multimorbidity. As with standard evidence synthesis, we plan to apply estimates of treatment efficacy from clinical trials to observational data representative of the target population. However, in most evidence synthesis it is assumed that estimates of relative treatment efficacy (RTE) from clinical trials can be applied, unmodified, to the target population. It is not known whether this assumption is valid in applying efficacy estimates to patients with multimorbidity.
In a limited number of large individual-patient meta-analyses (such as of aspirin for primary and secondary prevention) treatment efficacy was found to be similar across patient groups; RTE was similar regardless of cardiovascular risk factors, age and sex. However, for most drugs and conditions empirical evidence is lacking as to whether and how RTE differs between patients with and without comorbidity, especially for comorbidities which are not established causes or complications of the target disease.
Aim
Therefore, in this proposal we aim to examine and quantify the variation in relative treatment efficacy by comorbidity. We intend to do so by modelling such variation within clinical trials, then summarising this for drug-classes and wider groupings of related drug classes, for a range of comorbidities.
Objectives
Stage One – Produce trial-level summary estimates
1. Assign drugs to broad drug-classes based on 5-character ATC codes
2. Assign related drug-classes to wider drug-groupings – eg (B01 – antithrombotic drugs)
3. Identify comorbidities within individual clinical trials according to the Clinical Classification Software scheme[29] 4. For each trial estimate interactions between treatment allocation and age, sex and selected comorbidities
Stage Two – Analyse trial-level aggregated estimates
5. In Bayesian hierarchical generalized linear models, use the estimates from 4 to estimate average drug-class-level and drug-grouping level comorbidity-treatment interaction
6. Summarise 5 as a probability distribution for use in subsequent evidence synthesis; either as off-the-shelf informative priors for meta-analyses, or as inputs to probabilistic sensitivity analyses in which treatment effects are modelled
Study design
The study design involves first producing trial-level summary estimates (Objectives 1-4), and then meta-analysing these across studies (Objectives 5-6).
Stage One
Objective 1 Assign drugs to wider drug-classes
The trial inclusion/exclusion criteria are described in previous sections. We have already allocated all trial drugs for 202 selected trials to both an RXNORM code and, where a suitable code exists, a 7-digit WHO ATC code. We have then assigned each code to a less specific
5-character ATC code.
Objective 2 Related drug-classes to wider drug-groupings
Using clinical judgement, we have made a preliminary assignment of each 5-character drug- class to a wider drug-grouping (see relevant section). We will finalise the groupings within our steering committee prior to starting analyses.

Objective 3 Identify comorbidities within individual clinical trials according to the Clinical Classification Software scheme (similar to Elixhauser)
Comorbidities will be categorised using the Agency for Healthcare Research and Quality clinical classifications system (CCS). Having similar groupings to those used in the Elixhauser comorbidity scheme,[30] the CCS collapses WHO international Classification of Diseases (ICD-10) codes into groups. The CCS was originally developed in order to produce as clinically homogenous groupings as possible,[29] has been updated for ICD-10 and is used in research and health services reporting.[31] Having excluded those CCS groupings which are unlikely to have any impact on treatment effectiveness (eg code 200 “Other skin disorders” will be excluded), we will attempt to define in the trial datasets comorbid conditions from each of the 94 remaining grouping.
The majority of trials were not set-up to record comorbidities. As such, trial-specific operational definitions of each comorbidity will be defined using a combination of demographic, past medical history, lifestyle (eg smoking) and drug variables as well as information from trial protocols (ie inclusion and exclusion criteria). We will, where possible, assign an ICD-10 code as well as CCS group. However, for some trials and comorbidities only the latter, broader, definition will be feasible. We anticipate that it will frequently not be possible to arrive at an operational definition for many of the comorbidities.
As a sense check, we will also examine summary statistics for characteristics not included in the definition, but nonetheless related to the disease. For example, we would expect people with inflammatory arthropathy to have a higher prevalence of chronic pain than people without inflammatory arthropathy (except where collider-bias is an issue).
Where trials do clearly define and record comorbidities (eg the presence of spirometry- confirmed chronic obstructive pulmonary disease as a comorbidity), the sensitivity and specificity of our operational definitions will be estimated and reported.
This approach to defining variables is commonly used in routine-data research, a field in which members of our team have considerable expertise. While imperfect, this approach is an important first step in examining comorbidity-treatment interactions. We will take the following steps to make this process as robust as possible. First, each operational trial definition will be approved by our steering committee comprising clinicians, epidemiologists and statisticians. Secondly, we will not perform any statistical modelling or analyses including the outcome until these definitions have been agreed. Thirdly, we will maintain a database showing how each variable in the final dataset relates to the original trial variables, and will make this available to consumers of the research findings (along with the complete analysis code).
Fourthly, we will categorise each trial (using published eligibility criteria) as regards their inclusiveness with respect to the defined comorbidities, and will conduct sensitivity analyses after excluding moderately restrictive trials. Finally, we will make explicit the limitations arising from this approach, particularly the possibility of non-differential misclassification bias, in all study reports.
For each drug grouping we will model treatment effects by age and sex. The latter will be defined as per the study documentation.
Objective 4 Estimate interactions
For each outcome, we will model main effects and interactions with treatment allocation for age, sex, and up to 6 comorbidities. The comorbidities selected will be the 6 commonest for each drug-grouping. Where a particular trial does not have a comorbidity variable defined we will record that variable as missing.
For between-trial heterogeneity, the effect of scale and different transformations (logistic, log etc) has been extensively studied. However, we are not aware of any study which has examined the effect of different scales on the extent of heterogeneity in treatment-comorbidity

interactions between patients. Therefore, for continuous measures we will model outcomes on both the absolute and relative (log-transformed) scale, and for event outcome data we will model outcomes on the log-odds ratio log-rate ratio scales and log-risk ratio as well as log- hazard ratios scales. We will estimate hazard ratios using Cox regression, and for all other models will use Generalized Linear Models with appropriate link functions and error distributions.
All analyses will be conducted in R. We will obtain the coefficients and variance covariance matrices from each of these models. These model summaries will allow subsequent modelling of differences in treatment efficacy, by comorbidity, for drug classes and wider drug-groupings. For simplicity, missingness will be treated using complete case analysis. We will however record and report, for each operational comorbidity definition, the proportion of participants for whom sufficient data was missing to prevent a participant being defined as having a diagnosis. Where trials are missing definitions for particular comorbidities these will be encoded as missing and estimated within the Bayesian modelling. This is equivalent to assuming that data are missing at random.
Summary of outputs from stage one
In summary, therefore, the following results, all of which are trial-level aggregates/summaries, will be obtained from the above analyses:-
1. The proportion of participants with each combination of comorbidities
2. The proportion of participants with missing data included in the definition of each comorbidity
3. The coefficients and variance-covariance matrix of the Cox proportional hazard and generalized linear models described above.
Stage Two
Objective 5 Subsequent modelling
All subsequent modelling will be conducted on aggregated trial-level data.
In the second part of a two-step approach we will model the comorbidity-treatment interactions across multiple trials using the parameters described above as the dependent variables in Bayesian hierarchical generalized linear models (eg with a multivariate Gaussian likelihood).
The main effects for treatments and covariates will have independent priors for each trial, while the priors for the covariate-treatment interactions will have hyper-priors, to allow sharing of information. We have successfully fit such models on simulated data using Markov Chain Monte Carlo Methods in the JAGS package (http://mcmc-jags.sourceforge.net/) and using approximate methods in the R package, INLA package (http://www.r-inla.org/).
For each covariate-treatment interaction we will report the mean effect for each drug-class and drug grouping, along with the between drug-class variance. We will first model each comorbidity in turn, after which we will simultaneously model multiple comorbidities. We will separately examine associations for datasets comprising trials where a trial drug is compared with placebo, an agent from a different drug-class, and an agent from the same drug-class.
An assumption of this modelling approach is that comorbidity-treatment interactions are exchangeable for trials within drug-classes, and for drug-classes within wider drug groupings. This assumption makes use of the structure inherent in the anatomic therapeutic classification system; thereby allowing borrowing of information across drug-classes (eg antithrombotic agents).
The modelling is sufficiently flexible that, if there is no similarity in treatment-comorbidity interactions within our drug-groupings, the predicted comorbidity-treatment interaction for an unknown drug-class will simply have a wide uncertainty interval. This would indicate that little can be inferred about one drug class comorbidity-treatment interaction based on knowledge about such an interaction for another drug-class within that grouping.

These models will be fit in the JAGS package, using the GLM module. Alternative model specifications will be explored and compared using the deviance information criterion (DIC) and the Bayesian information criterion (BIC). Model convergence and autocorrelation will be assessed using diagnostic plots as well as summaries such as the Gelman-Rubin statistic.
Objective 6 – summarise comorbidity-treatment interactions as probability distributions
For all analyses, after convergence, a random sample from the model chains for the parameters of interest at the drug-class and drug-grouping level will be obtained. A model will be fit to these samples in R using non-linear least squares. Adequacy of the fit will be confirmed graphically. We will choose a distribution with not more than 3 parameters. In pilot analyses a t-distribution fit the MCMC samples very well.
We will retain these diagnostic plots to allow consumers of our research to check on the fit. Sample size calculations
We have not conducted a formal power calculation for estimating comorbidity-treatment interactions as we not aware of any analytical method for doing so, and analysing a large number of simulated datasets would have been impractical.
Instead we explored the feasibility of using a similar model to that shown above to estimate the mean comorbidity-treatment interaction across multiple drug-classes for both a categorical and continuous outcome. For both, an unspecified comorbidity was assumed to have a 20% prevalence, and for the continuous outcome the logit link and binomial distribution were substituted for the identity link and normal distribution.
We simulated null interactions for a categorical and continuous outcome and a 1.2-fold comorbidity-treatment interaction for the categorical outcome and a 2.5-unit comorbidity- treatment interaction for the continuous outcome. We recovered the original simulated effects. Additional assumptions are shown in the following table.
Outcome Categorical Continuous Number trials 23 68
Number participants 132,358 103,774 Baseline Risk = 0.2 Mean = 70 Treatment RR ~ unif(0.65 Diff ~ N(10, 1)
Comorbidity RR ~ unif (1.2 Diff ~ N(5, 0.5)
Null interaction – result OR 0.96; 95%CI Diff -0.01; 95%CI -0.8 to 0.77
Interaction present – result OR 1.22; 95%CI Diff 2.52; 95%CI 1.68 to 3.35 OR – odds ratio, RR relative risk, diff – difference on the absolute scale
Moreover, although clinicaldatarequest.com is the largest repository, we are applying to additional clinical trial data repositories. As such, for those drug-grouping where data are sparse, we are likely to be able to gain improvements in precision for the estimated comorbidity-treatment interactions by combining the summary estimates from these analyses with additional data.
Bias and confounding
Patients cannot be randomised to having or not having specific comorbidities. Hence, any observed differences in treatment efficacy by comorbidity may be caused by confounding. We will adjust these associations by age and sex but other variables, such as lifestyle factors, may confound the observed associations.
Moreover, clinical trials use double-blinding and other methods to ensure that follow-up and measurement not differential by randomisation status; no such steps are used to prevent differential misclassification by the presence/absence of comorbidity. As such, apparently weaker treatment effects could be due to greater misclassification in recording outcomes among people with specific comorbidities (eg in people with chronic obstructive pulmonary disease the presence of affective disorders may make exacerbations more difficult to diagnose).
We will therefore make these limitations clear in reporting of our findings. Nonetheless, these limitations are also features of pharmacoepidemiological approaches, the main alternative methodology which has been used to address this question. Moreover, pharmacoepidemiological approaches have the added problem of confounding by indication. A further caveat around causation is to note that, if treatment efficacy does differ by comorbidity, we will be unable to identify the specific mechanisms underlying this process.
Differences in treatment concordance, pharmacokinetics (eg in absorbance), the presence of drug-drug and drug-disease interactions and/or psychological factors modifying experience of certain outcomes (eg pain) could modify treatment efficacy in the presence of comorbidity.

Requested Studies:

A Randomized, Double-blind, Double-dummy, Placebo- and Active-controlled, Parallel Group Efficacy and Safety Comparison of 12-week Treatment of Two Doses (5 Mcg and 10 Mcg) of Tiotropium Inhalation Solution Delivered by the Respimat Inhaler, Placebo and Ipratropium Bromide Inhalation Aerosol (MDI) i
Data Contributor: Boehringer Ingelheim
Study ID: NCT00240435
Sponsor ID: 205.252

A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Efficacy and Safety Comparison of One-Year Treatment of Two Doses (5mg and 10mg) of Tiotropium Inhalation Solution Delivered by the Respimat Device in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00168844
Sponsor ID: 205.254

A Double-blind, Double-dummy, Placebo-controlled, Randomized, Three Parallel Groups Study Comparing the Efficacy, Safety and Tolerability of Pramipexole ER Versus Placebo and Versus Pramipexole IR Administered Orally Over a 26-week Maintenance Phase in Patients With Early Parkinsons Disease (PD).
Data Contributor: Boehringer Ingelheim
Study ID: NCT00479401
Sponsor ID: 248.524

A Randomized, Double-blind, Active (Pramipexole 0.5 mg Tid) and Placebo Controlled, Efficacy Study of Pramipexole Given 0.5 mg and 0.75 mg Bid Over a 12-week Treatment Phase in Early Parkinson’s Disease Patients (PramiBID)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00402233
Sponsor ID: 248.622

A Phase IV Randomised, Double-blind, Placebo-controlled, Dose Titration Trial With Pramipexole (Sifrol, Mirapexin) 0.125-0.75 mg/Day Per os to Investigate the Long-term Efficacy, Safety and Tolerability in Patients With Idiopathic Moderate to Severe Restless Legs Syndrome for 26 Weeks Followed by a 26 Week Open-label Extension Treatment Period
Data Contributor: Boehringer Ingelheim
Study ID: NCT00472199
Sponsor ID: 248.629

A Double-blind, Double-dummy, Placebo-controlled, Randomized, Three Parallel Groups Study Comparing the Efficacy, Safety and Tolerability of Pramipexole Extended Release (ER) Versus Placebo and Versus Pramipexole Immediate Release (IR) Administered Orally Over a 26-week Maintenance Phase in L-Dopa+ Treated Patients With Advanced Parkinsons Disease (PD).
Data Contributor: Boehringer Ingelheim
Study ID: NCT00466167
Sponsor ID: 248.525

A Randomized, Double-blind, Placebo-controlled, Parallel-group Clinical Trial to Examine the Efficacy and Safety of Early Pramipexole (PPX) Treatment Versus Delayed Pramipexole Treatment in Patients With New Onset Parkinson’s Disease.
Data Contributor: Boehringer Ingelheim
Study ID: NCT00321854
Sponsor ID: 248.595

A Randomised, Double-blind, Double Dummy, Active Controlled, Parallel Group, Forced Titration Study to Compare the Fixed-dose Combination of Telmisartan 80mg Plus Hydrochlorothiazide 25mg (T80/HCTZ25) Versus Telmisartan 80mg (T80) Monotherapy as First Line Therapy in Patients With Grade 2 or Grade 3 Hypertension (Systolic Blood Pressure (SBP) >=160 mmHg and Diastolic Blood Pressure (DBP) >=100 mmHg)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00926289
Sponsor ID: 502.550

A Randomized, Double-blind, Placebo-controlled Two-year Trial to Examine the Changes in Exercise Endurance and COPD Treated With Tiotropium Once Daily (EXACTT)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00525512
Sponsor ID: 205.368

Effect of Inhalation of Tiotropium Once Daily 18 Mcg Versus Salmeterol Twice Daily 50 Mcg on Time to First Exacerbation in COPD Patients (a Randomised, Double-blind, Double-dummy, Parallel Group, One-year Study).
Data Contributor: Boehringer Ingelheim
Study ID: NCT00563381
Sponsor ID: 205.389

A Prospective Randomised Open- Label Blinded-Endpoint (PROBE) Trial Comparing Telmisartan (MICARDIS®) (40-80-80mg QD) and Ramipril (2.5-5–10mg QD) in Patients With Mild-to-Moderate Hypertension Using Ambulatory Blood Pressure Monitoring. PRISMA = Prospective Randomised Investigation of the Safety and Efficacy of Micardis® vs Ramipril Using ABPM
Data Contributor: Boehringer Ingelheim
Study ID: NCT00274612
Sponsor ID: 502.391

A Prospective, Randomised, Double-blind, Double-dummy, Forced-titration, Multicentre, Parallel Group, One Year Treatment Trial to Investigate the Efficacy of Telmisartan 80 mg Versus Valsartan 160 mg in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy VIVALDI-Study
Data Contributor: Boehringer Ingelheim
Study ID: NCT00153023
Sponsor ID: 502.396

A Prospective, Randomized, Double-Blind, Forced Titration Trial to Compare the Efficacy of MICARDIS® (Telmisartan 80 mg p.o. Once Daily) and Diovan® (Valsartan 160 mg p.o. Once Daily) Using Ambulatory Blood Pressure Monitoring (ABPM) in Patients With Mild to Moderate Hypertension After Missing One Dose
Data Contributor: Boehringer Ingelheim
Study ID: NCT00034840
Sponsor ID: 502.327

A Randomised, Double-blind, Placebo-controlled, Multicenter Trial to Investigate the Preventive Effect of BIBR277 (Telmisartan) in Diabetic Nephropathy on Transition From Incipient to Overt Nephropathy – Incipient to Overt : Angiotensin 2 Receptor Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION Study –
Data Contributor: Boehringer Ingelheim
Study ID: NCT00153088
Sponsor ID: 502.413

A Prospective, Randomised, Open-Label, Blinded-Endpoint, Parallel Group, Multicentre, Forced-Titration, 14-Week Treatment Study Comparing MICARDIS® (Telmisartan 40-80-80 mg, QD) and ALTACE® (Ramipril 2.5-5-10 mg, QD) in Patients With Mild-to-Moderate Hypertension Using Ambulatory Blood Pressure Monitoring
Data Contributor: Boehringer Ingelheim
Study ID: NCT00274599
Sponsor ID: 502.392

A Prospective, Randomised, Double-blind, Double-dummy, Forced-titration, Multicentre, Parallel Group, One Year Treatment Trial to Compare MICARDIS® (Telmisartan) 80 mg Versus COZAAR® (Losartan) 100 mg, in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy (AMADEO Study)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00168857
Sponsor ID: 502.397

Spiriva Assessment of FEV1 – (SAFE-Portugal). The Effect of Inhaled Tiotropium Bromide (18 Mcg Once Daily) on the Change in FEV1 During Treatment in Patients With COPD. A Three-month Parallel Group, Double-blind, Randomised, Placebo-controlled Study.
Data Contributor: Boehringer Ingelheim
Study ID: NCT00239408
Sponsor ID: 205.282

Effects of Inhaled Tiotropium Bromide on Severity of Airflow Obstruction During Long-term Treatment in Patients With Moderately Severe Copd. Impact on Severity and Incidence of Exacerbations.
Data Contributor: Boehringer Ingelheim
Study ID: NCT00274014
Sponsor ID: 205.214

A Six-Week, Randomized, Double-Blind, Quadruple-Dummy Parallel Group Multiple Dose Study Comparing the Efficacy and Safety of Tiotropium Inhalation Capsules Plus Formoterol Inhalation Capsules to Salmeterol Inhalation Aerosol Plus Fluticasone Inhalation Aerosol in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00239421
Sponsor ID: 205.287

A Randomized, Double-blind, Placebo-controlled, Parallel Group Trial Assessing the Proportion of Patients Experiencing an Exacerbation and Proportion of Patients Hospitalized for an Exacerbation Over 6 Months During Treatment With Tiotropium 18 Mcg Capsule Once Daily in Patients With COPD in a Veterans Affairs Setting
Data Contributor: Boehringer Ingelheim
Study ID: NCT00274547
Sponsor ID: 205.266

Effect of a 9-month Treatment of SPIRIVA® on Health Related Quality of Life in Patients With Chronic Obstructive Pulmonary Disease. Validation of a New HRQoL Questionnaire Appropriate to Common Daily Practice. (TIPHON Study)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00274053
Sponsor ID: 205.256

A Multiple Dose Comparison of Tiotropium Inhalation Capsules and Salmeterol Inhalation Aerosol in a 12 Week, Randomized, Double-Blind, Double-Dummy Parallel Group Study in Patients With Chronic Obstructive Pulmonary Disease (COPD).
Data Contributor: Boehringer Ingelheim
Study ID: NCT00274560
Sponsor ID: 205.264

Spiriva® Assessment of FEV1 (SAFE). The Effect of Inhaled Tiotropium Bromide (18 Mcg Once Daily) on the Change in FEV1 During Long-term Treatment in Patients With COPD. A One-year Parallel Group, Double-blind, Randomised, Placebo-controlled Study
Data Contributor: Boehringer Ingelheim
Study ID: NCT00277264
Sponsor ID: 205.259

Acute and Long-term Effects of Once Daily Oral Inhalation of Tiotropium 18 Mcg Dry Powder Inhalation Capsules in a Placebo Controlled Parallel Group Design Study in Patients With Chronic Obstructive Pulmonary Disease (COPD) of Different Severity
Data Contributor: Boehringer Ingelheim
Study ID: NCT00274573
Sponsor ID: 205.257

A Six Month, Randomized, Double-blind (Within Formulation), Multiple Dose Trial to Compare the Safety and Efficacy of 20 mcg and 40 mcg of Ipratropium Bromide, as Delivered by the RESPIMAT Device, to 18 mcg ATROVENT® Inhalation Aerosol (x 2 Puffs) and Respective Placebos in Adults, With Chronic Obstructive Pulmonary Disease
Data Contributor: Boehringer Ingelheim
Study ID: NCT02177344
Sponsor ID: 244.2484

A Randomised, Double- Blind, Placebo-controlled, 6 Week Parallel-group Trial on the Efficacy and Safety of the Angiotensin II Receptor Antagonist Micardis® (Telmisartan 20 mg, 40 mg or 80 mg, p.o. Once Daily) or Hydrochlorothiazide 12.5 mg p.o. Once Daily in the Management of Patients With Isolated Systolic Hypertension (ISH). (ARAMIS – Study = Angiotensin II Receptor Antagonist Micardis in Isolated Systolic Hypertension)
Data Contributor: Boehringer Ingelheim
Study ID: NCT02175355
Sponsor ID: 502.254

A PROBE (Prospective, Randomised, Open-Label, Blinded Endpoint) Trial to Investigate the Efficacy and Safety of Telmisartan 40-80mg Once Daily Compared With 10-20 mg Enalapril Once Daily Over a Period of 24 Weeks in Elderly Patients With Blood Hypertension
Data Contributor: Boehringer Ingelheim
Study ID: NCT02177461
Sponsor ID: 502.317

A Prospective Randomized Open-Label Blinded End Point (PROBE) Trial Comparing MICARDIS® (Telmisartan) (80 mg QD) and Valsartan (80 mg QD) in Patients With Mild-to-Moderate Hypertension Using Ambulatory Blood Pressure Monitoring.
Data Contributor: Boehringer Ingelheim
Study ID: NCT02177396
Sponsor ID: 502.256

A Phase IIIb-IV, Randomised, Open Label Trial on Efficacy and Safety of 2 Parallel Groups: Full Dose Tenecteplase Combined With Unfractionated Heparin or Enoxaparin in Acute Myocardial Infarction in the Prehospital Setting (ASSENT 3 Plus) ASSENT 3 Plus Was a Satellite Study to ASSENT 3 (Main Study) ASSENT (ASsessment of the Safety and Efficacy of New Thrombolytic Regimens)
Data Contributor: Boehringer Ingelheim
Study ID: NCT02181998
Sponsor ID: 1123.11

A Multiple Dose Comparison of Tiotropium Inhalation Capsules, Salmeterol Inhalation Aerosol and Placebo in a Six-Month, Double-Blind, Double-Dummy, Safety and Efficacy Study in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT02172287
Sponsor ID: 205.130

A Phase 3 Study to Evaluate the Efficacy and Safety of Dexlansoprazole MR (30 mg QD and 60 mg QD) Compared to Placebo on Symptom Relief in Subjects With Symptomatic Nonerosive Gastroesophageal Reflux Disease (GERD)
Data Contributor: Takeda
Study ID: NCT00321984
Sponsor ID: T-GD05-137

A Phase 3 Multicenter, Randomized, Double-Blind, Parallel Group, Placebo Controlled Trial to Evaluate the Efficacy of TAK-390MR (30 mg QD) Compared to Placebo on Relief of Nocturnal Heartburn in Subjects With Symptomatic Gastroesophageal Reflux Disease (GERD)
Data Contributor: Takeda
Study ID: NCT00627016
Sponsor ID: T-GD07-170

A Phase 3, Open-Label Study to Assess the Long-Term Safety of Dexlansoprazole MR (60 mg QD and 90 mg QD)
Data Contributor: Takeda
Study ID: NCT00255190
Sponsor ID: T-GI04-088

A Phase 3 Study to Evaluate the Efficacy and Safety of TAK-390MR (60 mg Once- Daily [QD] and 90 mg QD) and an Active Comparator, Lansoprazole (30 mg QD) on Healing of Erosive Esophagitis
Data Contributor: Takeda
Study ID: NCT00251693
Sponsor ID: T-EE04-084

A Phase 3 Study to Evaluate the Efficacy and Safety of TAK-390MR (60 mg Once-daily [QD] and 90 mg QD) and an Active Comparator, Lansoprazole (30 mg QD) on Healing of Erosive Esophagitis
Data Contributor: Takeda
Study ID: NCT00251719
Sponsor ID: T-EE04-085

A Phase 3 Study to Evaluate the Safety and Efficacy of Dexlansoprazole MR (60 mg QD and 90 mg QD) Compared to Placebo in Maintenance of Healing in Subjects With Healed Erosive Esophagitis
Data Contributor: Takeda
Study ID: NCT00255164
Sponsor ID: T-EE04-086

A Phase 3 Study to Evaluate the Safety and Efficacy of TAK-390MR (30 mg QD and 60 mg QD) Compared to Placebo in Maintenance of Healing in Subjects With Healed Erosive Esophagitis.
Data Contributor: Takeda
Study ID: NCT00321737
Sponsor ID: T-EE05-135

A Phase 3 Study to Evaluate the Efficacy and Safety of Dexlansoprazole MR (60 mg Once-Daily (QD) and 90 mg QD) Compared to Placebo on Symptom Relief in Subjects With Symptomatic Non-Erosive Gastroesophageal Reflux Disease (GERD)
Data Contributor: Takeda
Study ID: NCT00251745
Sponsor ID: T-GD04-082

A Phase 3 Study to Evaluate the Efficacy and Safety of Dexlansoprazole MR (60 mg QD and 90 mg QD) Compared to Placebo on Symptom Relief in Subjects With Symptomatic Non-Erosive Gastroesophageal Reflux Disease (GERD)
Data Contributor: Takeda
Study ID: NCT00251758
Sponsor ID: T-GD04-083

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients With Moderate to Severe Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT00783718
Sponsor ID: C13006

Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis
Data Contributor: UCB
Study ID: NCT01087762
Sponsor ID: AS001

Phase 3, Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Subjects With Adult-Onset Active and Progressive Psoriatic Arthritis (PsA)
Data Contributor: UCB
Study ID: NCT01087788
Sponsor ID: PsA001

Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 48 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL (5 mcg [2 Actuations of 2.5 mcg] and 10 mcg [2 Actuations of 5 mcg]) Delivered by the Respimat® Inhaler, in Patients With Chronic Obstructive Pulmonary Disease (COPD
Data Contributor: Boehringer Ingelheim
Study ID: NCT00782509
Sponsor ID: 1222.12

Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 48 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL (5 mcg [2 Actuations of 2.5 mcg] and 10 mcg [2 Actuations of 5 mcg]) Delivered by the Respimat® Inhaler, in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00782210
Sponsor ID: 1222.11

A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 48 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL (5 µg [2 Actuations of 2.5 ug] and 10 ug [2 Actuations of 5 ug]) Delivered by the Respimat® Inhaler, and 48 Weeks of Twice Daily Foradil® (12 µg) Delivered by the Aerolizer® Inhaler, in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00793624
Sponsor ID: 1222.13

A Prospective, Randomized, Double-Blind, Double-Dummy, Titration-to-Response Trial Comparing MICARDIS® (Telmisartan) (40 & 80 mg QD) and COZAAR® (Losartan) (50 & 100 mg QD) in Patients With Mild-to-Moderate Hypertension Using Ambulatory Blood Pressure Monitoring
Data Contributor: Boehringer Ingelheim
Study ID: NCT02200640
Sponsor ID: 502.343

A Prospective, Randomised, Double-Blind, Double-Dummy, Titration-to-Response Trial Comparing MICARDIS® (Telmisartan) (40 or 80 mg p.o. Once Daily) and COZAAR® / LORZAAR® (Losartan) (50 or 100 mg p.o. Once Daily) in Patients With Mild-to-Moderate Hypertension Using Ambulatory Blood Pressure Monitoring (TOPAS STUDY = Telmisartan and LOsartan ComParative ABPM Study)
Data Contributor: Boehringer Ingelheim
Study ID: NCT02200653
Sponsor ID: 502.344

A Randomised, Double-blind, Parallel Group, 12 Week Study, Comparing the Effect of Once Daily Tiotropium Lactose Capsule With Placebo in Patients With Chronic Obstructive Pulmonary Disease (COPD), naïve to Anticholinergic Agents in Addition to Receiving Their Usual COPD Care
Data Contributor: Boehringer Ingelheim
Study ID: NCT00274079
Sponsor ID: 205.276

A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of BI 10773 (10 mg and 25 mg Administered Once Daily) as Add on to Pre-existing Antidiabetic Therapy Over 52 Weeks in Patients With Type 2 Diabetes Mellitus and Renal Impairment and Insufficient Glycaemic Control
Data Contributor: Boehringer Ingelheim
Study ID: NCT01164501
Sponsor ID: 1245.36

A Phase III Randomised, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of BI 10773 (10 mg, 25 mg) Administered Orally, Once Daily Over 12 Weeks in Hypertensive Patients With Type 2 Diabetes Mellitus
Data Contributor: Boehringer Ingelheim
Study ID: NCT01370005
Sponsor ID: 1245.48

A Multi-Center, Randomized, Parallel-Group, Open-Label Study to Compare Prescription Non-Steroidal Anti-Inflammatory Drug (NSAID) Changes, Health Care Utilization, Efficacy and Safety of Meloxicam 7.5 mg Versus Usual Care Administration of Prescription NSAIDs in a Managed Healthcare Setting in Patients With Osteoarthritis of the Hip, Knee, Hand or Spine
Data Contributor: Boehringer Ingelheim
Study ID: NCT02183064
Sponsor ID: 107.210

A Double-blind, Double-dummy, Randomised, Parallel-group Study Comparing the Efficacy, Safety and Tolerability of Pramipexole Extended Release Versus Pramipexole Immediate Release Administered Orally for 18 Weeks in Chinese Parkinson’s Disease (PD) Patients Who Can be Concomitantly Treated With Levodopa
Data Contributor: Boehringer Ingelheim
Study ID: NCT01191944
Sponsor ID: 248.671

A Prospective, Randomised, Double-blind, Double-dummy Trial to Compare the Efficacy of Micardis® (Telmisartan) (80 mg p.o. Once Daily) and Valsartan (160 mg p.o. Once Daily) in Patients With Mild-to-moderate Hypertension After Missing One Dose Using Ambulatory Blood Pressure Monitoring
Data Contributor: Boehringer Ingelheim
Study ID: NCT02242318
Sponsor ID: 502.376

A Randomized, Active-controlled, Double-blind, Double-dummy, Parallel Group Design, Multi-center Trial to Compare the Efficacy and Safety of 2.5 µg and 5 µg Tiotropium Inhalation Solution Delivered by the Respimat Inhaler With Tiotropium Inhalation Capsules 18 µg Delivered by the HandiHaler (TIOSPIR)
Data Contributor: Boehringer Ingelheim
Study ID: NCT01126437
Sponsor ID: 205.452

A Randomised, Double Blind, Parallel Group Study to Assess the Efficacy and Safety of 12 Weeks of Once Daily, Orally Inhaled, Co-administration of Olodaterol 5µg (Delivered by the Respimat® Inhaler) and Tiotropium 18µg (Delivered by the HandiHaler®) Compared to Once Daily, Orally Inhaled, Co-administration of Placebo (Delivered by the Respimat® Inhaler) and Tiotropium 18µg (Delivered by the HandiHaler®) in Patients With Chronic Obstructive Pulmonary Disease (COPD)[ANHELTO TM 1]
Data Contributor: Boehringer Ingelheim
Study ID: NCT01694771
Sponsor ID: 1222.51

A 52 Weeks, Double Blind, Randomized, Placebo-controlled Trial Evaluating the Effect of Oral BIBF 1120, 150 mg Twice Daily, on Annual Forced Vital Capacity Decline, in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Data Contributor: Boehringer Ingelheim
Study ID: NCT01335464
Sponsor ID: 1199.32

A Phase 3, Randomized, Multicenter, Allopurinol and Placebo-Controlled Study Assessing the Safety and Efficacy of Oral Febuxostat in Subjects With Gout.
Data Contributor: Takeda
Study ID: NCT00174915
Sponsor ID: C02-009

A Phase 3, Randomized, Multicenter Study Comparing the Safety and Efficacy of Oral Febuxostat Versus Allopurinol in Subjects With Gout
Data Contributor: Takeda
Study ID: NCT00102440
Sponsor ID: C02-010

A Phase 3, Open-Label, Randomized, Allopurinol-Controlled Study to Assess the Long-Term Safety of Oral Febuxostat in Subjects With Gout
Study ID: NCT00175019
Sponsor ID: C02-021
Data Contributor: Takeda

A Phase 3, Randomized, Multicenter, Double-Blind, Allopurinol-Controlled Study Assessing the Efficacy and Safety of Oral Febuxostat in Subjects With Gout.
Data Contributor: Takeda
Study ID: NCT00430248
Sponsor ID: F-GT06-153

A 12-week Randomised, Double Blind, Placebo Controlled, Parallel Group Trial Evaluating the Efficacy and Safety of Inhaled Tiotropium 18μg q.d. in Patients With COPD and a Concomitant Diagnosis of Asthma
Data Contributor: Boehringer Ingelheim
Study ID: NCT00152984
Sponsor ID: 205.301

A PROBE (Prospective, Randomised, Open-label, Blinded Endpoint) Trial to Investigate the Efficacy and Safety of Telmisartan 40-80 mg Once Daily Compared With Losartan 50-100 mg Once Daily Over a Period of 12 Weeks, and of Telmisartan 80 mg + HCTZ 12.5 mg Once Daily Compared With Losartan 100 mg Once Daily + HCTZ 12.5 mg Once Daily Over a Period of Further 12 Weeks in Mild to Moderate Hypertensive Patients (Grade 1 and Grade 2 WHO-ISH Guidelines 1999)
Data Contributor: Boehringer Ingelheim
Study ID: NCT02172586
Sponsor ID: 502.316

A Phase III Randomised, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate Efficacy and Safety of Tiotropium Inhalation Solution Delivered Via Respimat® Inhaler (5 mcg/Day) Over 48 Weeks as add-on Controller Therapy on Top of Usual Care in Patients With Severe Persistent Asthma
Data Contributor: Boehringer Ingelheim
Study ID: NCT00776984
Sponsor ID: 205.417

Phase IIIb, Multinational, Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of Certolizumab Pegol, a Pegylated Fab’ Fragment of a Humanized Anti-Tumor Necrosis Factor(TNF)-Alpha Monoclonal Antibody, Administered in Subjects With Moderately to Severely Active Crohn’s Disease.
Data Contributor: UCB
Study ID: NCT00552058
Sponsor ID: C87085

A Multi-center, Double-blind, Parallel-group, Placebo Controlled, Randomized Study: Evaluation of the Efficacy and Safety of Brivaracetam in Subjects (>= 16 to 70 Years Old) With Partial Onset Seizures.
Data Contributor: UCB
Study ID: NCT00490035
Sponsor ID: N01252

An International, Double-blind, Parallel-group, Placebo-controlled, Randomized Study: Evaluation of the Efficacy and Safety of Brivaracetam in Subjects (>= 16 to 70 Years Old) With Partial Onset Seizures
Data Contributor: UCB
Study ID: NCT00464269
Sponsor ID: N01253

A Randomised, Double-blind, Active-controlled Study to Evaluate the Impact of Stepwise Withdrawal of Inhaled Corticosteroid Treatment in Patients With Severe to Very Severe Chronic Obstructive Pulmonary Disease (COPD) on Optimized Bronchodilator Therapy
Data Contributor: Boehringer Ingelheim
Study ID: NCT00975195
Sponsor ID: 352.2046

A 24-week Phase III Randomized, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Twice Daily Oral Administration of Empagliflozin + Metformin Compared With the Individual Components of Empagliflozin or Metformin in Drug Naive Patients With Type 2 Diabetes Mellitus
Data Contributor: Boehringer Ingelheim
Study ID: NCT01719003
Sponsor ID: 1276.1

A Multicenter, Randomized, Double-Blind, Active-Controlled Study to Evaluate the Durability of the Efficacy and Safety of Alogliptin Compared to Glipizide When Used in Combination With Metformin in Subjects With Type 2 Diabetes
Data Contributor: Takeda
Study ID: NCT00856284
Sponsor ID: SYR-322_305

A Randomized, Open-Label, Parallel-Arm, Noninferiority Comparison of the Effects of Two Doses of LY2189265 and Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes on Stable Doses of Metformin and Glimepiride
Data Contributor: Lilly
Study ID: NCT01075282
Sponsor ID: 11374

A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Induction Dosing Period Followed by a Randomized Maintenance Dosing Period and a Long- Term Extension Period to Evaluate the Efficacy and Safety of LY2439821 in Patients With Moderate-to-Severe Plaque Psoriasis
Data Contributor: Lilly
Study ID: NCT01474512
Sponsor ID: 12972

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients With Moderate-to-Severe Plaque Psoriasis
Data Contributor: Lilly
Study ID: NCT01597245
Sponsor ID: 12973

A 12-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients With Moderate to Severe Plaque Psoriasis With a Long-Term Extension Period
Data Contributor: Lilly
Study ID: NCT01646177
Sponsor ID: 13685

PHIRST-1: Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Phosphodiesterase Type 5 (PDE5) Inhibitor Tadalafil in the Treatment in Patients With Pulmonary Arterial Hypertension
Data Contributor: Lilly
Study ID: NCT00125918
Sponsor ID: 10303

A Phase 3, Randomized, Double Blind, Placebo and Tamsulosin Controlled, Parallel Design, Multinational Study to Evaluate the Efficacy and Safety of Tadalafil Once a Day Dosing for 12 Weeks in Asian Men With Signs and Symptoms of Benign Prostatic Hyperplasia
Data Contributor: Lilly
Study ID: NCT00861757
Sponsor ID: 10487

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, 5-Group, Multinational Study to Evaluate the Efficacy, Dose Response, and Safety of Tadalafil Once-a-Day Dosing for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia
Data Contributor: Lilly
Study ID: NCT00384930
Sponsor ID: 9797

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multinational Study to Evaluate the Efficacy and Safety of Daily Tadalafil for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia
Data Contributor: Lilly
Study ID: NCT00827242
Sponsor ID: 10893

A Randomized, Double-Blind, Placebo-Controlled, Parallel Design, Multinational Study to Evaluate the Efficacy and Safety of Tadalafil 2.5 and 5 mg Once Daily Dosing for 12 Weeks for the Treatment of Erectile Dysfunction and Signs and Symptoms of Benign Prostatic Hyperplasia in Men With Both Erectile Dysfunction and Benign Prostatic Hyperplasia
Data Contributor: Lilly
Study ID: NCT00855582
Sponsor ID: 11667

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Study to Evaluate the Safety and Efficacy of Daily Tadalafil for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia on Concomitant Alpha1-Adrenergic Blocker Therapy
Data Contributor: Lilly
Study ID: NCT00848081
Sponsor ID: 11668

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Global Multicenter Study to Evaluate the Efficacy and Safety of Tadalafil Once Daily Dosing for 12 Weeks in Men With Signs and Symptoms of Benign Prostatic Hyperplasia
Data Contributor: Lilly
Study ID: NCT00970632
Sponsor ID: 12932

A Randomized, Parallel-Arm, Double-Blinded Study Comparing the Effect of Once-Weekly Dulaglutide With Placebo in Patients With Type 2 Diabetes Mellitus on Sulfonylurea Therapy (AWARD-8: Assessment of Weekly AdministRation of LY2189265 in Diabetes – 8)
Data Contributor: Lilly
Study ID: NCT01769378
Sponsor ID: 13193

A Randomized, Open-Label, Parallel-Arm Study Comparing the Effect of Once-Weekly Dulaglutide With Once-Daily Liraglutide in Patients With Type 2 Diabetes (AWARD-6: Assessment of Weekly AdministRation of LY2189265 in Diabetes-6)
Data Contributor: Lilly
Study ID: NCT01624259
Sponsor ID: 11377

The Impact of LY2189265 Versus Insulin Glargine in Combination With Insulin Lispro for the Treatment to Target of Type 2 Diabetes Mellitus (AWARD-4: Assessment of Weekly AdministRation of LY2189265 in Diabetes – 4)
Data Contributor: Lilly
Study ID: NCT01191268
Sponsor ID: 11376

The Impact of LY2189265 Versus Metformin on Glycemic Control in Early Type 2 Diabetes Mellitus (AWARD-3: Assessment of Weekly AdministRation of LY2189265 in Diabetes-3)
Data Contributor: Lilly
Study ID: NCT01126580
Sponsor ID: 11375

A Randomized, Placebo-Controlled Comparison of the Effects of Two Doses of LY2189265 or Exenatide on Glycemic Control in Patients With Type 2 Diabetes on Stable Doses of Metformin and Pioglitazone (AWARD-1: Assessment of Weekly Administration of LY2189265 in Diabetes-1)
Data Contributor: Lilly
Study ID: NCT01064687
Sponsor ID: 11373

A Phase 2/3, Placebo-Controlled, Efficacy and Safety Study of Once-Weekly, Subcutaneous LY2189265 Compared to Sitagliptin in Patients With Type 2 Diabetes Mellitus on Metformin
Data Contributor: Lilly
Study ID: NCT00734474
Sponsor ID: 11422

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Cardiovascular Outcomes Following Treatment With Alogliptin in Addition to Standard of Care in Subjects With Type 2 Diabetes and Acute Coronary Syndrome
Data Contributor: Takeda
Study ID: NCT00968708
Sponsor ID: SYR-322_402

Comparison of the Effects of Teriparatide With Those of Alendronate Sodium on Lumbar Spine Bone Mineral Density in Glucocorticoid-Induced Osteoporosis
Data Contributor: Lilly
Study ID: NCT00051558
Sponsor ID: 6484

Effects of LY333334 in the Treatment of Postmenopausal Women With Osteoporosis
Data Contributor: Lilly
Study ID: NCT00670501

Comparison of Raloxifene Hydrochloride and Placebo in the Treatment of Postmenopausal Women With Osteoporosis
Data Contributor: Lilly
Study ID: NCT00670319
Sponsor ID: 1363

A Double-Blind, Randomized, Parallel-Group Study to Compare the Efficacy and Safety of TAK-491 With Valsartan in Subjects With Essential Hypertension
Data Contributor: Takeda
Study ID: NCT00591578
Sponsor ID: TAK-491_301

A Double-Blind, Randomized, Parallel-Group Study to Compare the Efficacy and Safety of TAK-491 With Ramipril in Subjects With Essential Hypertension
Data Contributor: Takeda
Study ID: NCT00760214
Sponsor ID: 01-06-TL-491-020

A Double-Blind, Randomized, Placebo-Controlled, 5-Arm Titration Study to Evaluate the Efficacy and Safety of TAK-491 When Compared With Valsartan and Olmesartan in Subjects With Essential Hypertension
Data Contributor: Takeda
Study ID: NCT00696436
Sponsor ID: 01-06-TL-491-019

An 8-Month Phase 3, Open-Label Study With a Blinded Reversal Phase to Evaluate the Safety and Tolerability of TAK-491 in Subjects With Essential Hypertension
Data Contributor: Takeda
Study ID: NCT00696384
Sponsor ID: 01-06-TL-491-016

A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-491 in Black Subjects With Essential Hypertension
Data Contributor: Takeda
Study ID: NCT00591253
Sponsor ID: 01-06-TL-491-011

A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-491 When Co-administered With Amlodipine 5 mg in Subjects With Essential Hypertension
Data Contributor: Takeda
Study ID: NCT00591266
Sponsor ID: 01-05-TL-491-010

A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-491 When Co-administered With Chlorthalidone in Subjects With Essential Hypertension
Data Contributor: Takeda
Study ID: NCT00591773
Sponsor ID: 01-05-TL-491-009

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-491 in Subjects With Essential Hypertension
Data Contributor: Takeda
Study ID: NCT00696241
Sponsor ID: 01-05-TL-491-008

A Ph II/III Seamless, Multi-center, Randomized, Double-blind, Placebo-controlled Study of the Reduction in Signs and Symptoms and Inhibition of Structural Damage During Treatment With Tocilizumab Versus Placebo in Patients With Ankylosing Spondylitis Who Have Failed Non-steroidal Anti-inflammatory Drugs and Are naïve to TNF Antagonist Therapy NSAIDs
Data Contributor: Roche
Study ID: NCT01209702
Sponsor ID: NA22823

A Randomized, Double-blind Study of Safety and Prevention of Structural Joint Damage During Treatment With Tocilizumab Versus Placebo, in Combination With Methotrexate, in Patients With Moderate to Severe Rheumatoid Arthritis
Data Contributor: Roche
Study ID: NCT00106535
Sponsor ID: WA17823

A Multi-center, Randomized, Blinded, Parallel-group Study of the Reduction of Signs and Symptoms During Monotherapy Treatment With Tocilizumab 8 mg/kg Intravenously Versus Adalimumab 40 mg Subcutaneously in Patients With Rheumatoid Arthritis
Data Contributor: Roche
Study ID: NCT01119859
Sponsor ID: WA19924

A Multi-center, Randomized, Double-blind, Parallel Group Study of the Safety, Disease Remission and Prevention of Structural Joint Damage During Treatment With Tocilizumab (TCZ), as a Monotherapy and in Combination With Methotrexate (MTX), Versus Methotrexate in Patients With Early, Moderate to Severe Rheumatoid Arthritis
Data Contributor: Roche
Study ID: NCT01007435
Sponsor ID: WA19926

A Randomized, Double-blind, Parallel Group Study of Safety and the Effect on Clinical Outcome of Tocilizumab Subcutaneous (sc) Versus Placebo sc in Combination With Traditional Disease Modifying Anti-rheumatic Drugs (DMARDs) in Patients With Moderate to Severe Active Rheumatoid Arthritis
Data Contributor: Roche
Study ID: NCT01232569
Sponsor ID: NA25220

A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Efficacy and Safety of Xolair® (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Antihistamine Treatment (H1)
Data Contributor: Roche
Study ID: NCT01287117
Sponsor ID: Q4881g

A Phase III, Multicenter, Randomized, Double-blind, Dose-ranging, Placebo-controlled Study to Evaluate the Efficacy, Response Duration and Safety of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria Who Remain Symptomatic Despite Antihistamine Treatment (H1)
Data Contributor: Roche
Study ID: NCT01292473
Sponsor ID: Q4882g

A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Safety Study of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic Despite Treatment With H1 Antihistamines, H2 Blockers, and/or Leukotriene Receptor Antagonists
Data Contributor: Roche
Study ID: NCT01264939
Sponsor ID: Q4883g

Public Disclosures:

Jennifer Lees. The impact of age, sex, comorbidity count and race/ethnicity on attrition and screen failure from trials. Kidney Health Symposium 2023, Event held on 24th Feb 2023. (From 34-58 mins).https://ctc.usyd.edu.au/news-events/kidney-health-symposium-2023/
Lees, J.S., Crowther, J., Hanlon, P., Butterly, E., Wild, S., Mair, F.S., Guthrie, B., Gillies, K., Dias, S., Welton, N.J. and Katikireddi, S.V., 2023. Participant characteristics and exclusion from trials: a meta-analysis of individual participant-level data from phase 3/4 industry-funded trials in chronic medical conditions. medRxiv, pp.2023-04. Doi: 10.1101/2023.04.14.23288549