Exploratory Trials Research Articles

A conceptual framework for eco-friendly paddy farming in Taiwan, based on experimentation with System of Rice Intensification (SRI) methodology

This paper reviews the constraints and challenges of paddy farming in Taiwan. Based on those evidences, a set of eco-friendly rice farming practices raised by SRI principles are proposed from exploratory SRI trials conducted in Taiwan. The trials show that even with less exact leveling in the SRI field than is ideally provided, the average yield for SRI was higher than for CP; with an aerobic soil situation, the combination of biocontrol agent application and SRI management was seen to give better rice blast control; and the highest paddy yield was obtained from single-seedling transplants from potted nursery trays which protect the young seedlings’ roots from shock or twisting, compared with the planting of more numerous seedlings grown on flat nursery trays by a mechanical rice transplanter. In conclusion, a conceptual framework for eco-friendly paddy farming is formulated to encourage farmers to practice SRI principles. Among the participants in this collaboration, a co-operating group of SRI farmers is organized under investor sponsorship to guarantee the quality and safety of food, integrating an inspection service and food-source traceability from field to market with the production process. It is seen that in Taiwan, SRI principles can be adopted by local farmers without need for additional premiums through eco-friendly collaboration that can raise simultaneously the productivity of land, capital, and irrigation water. In addition, this collaboration can take advantage of increasing consumer demand for safe food with fewer chemicals and for supporting a greater level of biodiversity.

Bayesian sample sizes for exploratory clinical trials comparing multiple experimental treatments with a control.

In this paper, a Bayesian approach is developed for simultaneously comparing multiple experimental treatments with a common control treatment in an exploratory clinical trial. The sample size is set to ensure that, at the end of the study, there will be at least one treatment for which the investigators have a strong belief that it is better than control, or else they have a strong belief that none of the experimental treatments are substantially better than control. This criterion bears a direct relationship with conventional frequentist power requirements, while allowing prior opinion to feature in the analysis with a consequent reduction in sample size. If it is concluded that at least one of the experimental treatments shows promise, then it is envisaged that one or more of these promising treatments will be developed further in a definitive phase III trial. The approach is developed in the context of normally distributed responses sharing a common standard deviation regardless of treatment. To begin with, the standard deviation will be assumed known when the sample size is calculated. The final analysis will not rely upon this assumption, although the intended properties of the design may not be achieved if the anticipated standard deviation turns out to be inappropriate. Methods that formally allow for uncertainty about the standard deviation, expressed in the form of a Bayesian prior, are then explored. Illustrations of the sample sizes computed from the new method are presented, and comparisons are made with frequentist methods devised for the same situation.

New medications in development for the treatment of hyperuricemia of gout.

To update recent developments in medications targeting hyperuricemia, but not including medications recently labelled in the European Union and the United States. A new xanthine oxidase inhibitor, Topiloric (Fujiyakuhin Co., Ltd. Japan) Uriadec (Sanwa Kagaku Kenkyusho Co., Ltd. Japan), has been developed and labelled in Japan. An inhibitor of purine nucleoside phosphorylase, Ulodesine, is in development in combination with allopurinol. The rest of the medications in the pipeline for hyperuricemia are targeting renal transporters of uric acid, mainly URAT1 and OAT4, acting as uricosuric agents. Most of them, such as lesinurad and arhalofenate, are being tested in trials in combination with allopurinol and febuxostat. The most potent RDEA3170 is being tested in monotherapy, but also associated with febuxostat. Recently, medications showing dual activity, inhibiting both xanthine oxidoreductase and URAT1, have been communicated or started exploratory clinical trials. There is no report of medications targeting other transporters such as Glut9 or ABCG2. There are a number of medications in the pipeline targeting hyperuricemia, mostly uricosurics in combination with xanthine oxidase inhibitors, but some targeting both xanthine oxidoreductase and URAT1. Increasing the number of available medications will ensure proper control of hyperuricemia to target serum urate levels in the near future for most, if not all, patients with hyperuricemia.

Impact of probiotic Lactobacillus plantarum TENSIA in different dairy products on anthropometric and blood biochemical indices of healthy adults.

The blood pressure-lowering effect of dairy products holds the potential to decrease the risk of cardiovascular disease (CVD). An open question is if the successful expression of functional properties of the probiotic strain depends on host biomarkers and/or food matrix properties. The probiotic Lactobacillus plantarum strain TENSIA® (DSM 21380) is a novel microorganism with antimicrobial and antihypertensive functional properties. The aim of this study was to characterise the functional properties of the probiotic L. plantarum TENSIA and compare its effects on host anthropometric, clinical, and blood biomarkers when consumed with cheese or yoghurt. This study involved two double-blinded randomised placebo-controlled exploratory trials (ISRCTN15061552 and ISRCTN79645828) of healthy adults over a three-week period. The three-week consumption of probiotic L. plantarum TENSIA in a daily dose of 1×1010 cfu in probiotic cheese or a daily dose of 6×109 cfu in yoghurt with different content of carbohydrates, proteins, and lipids did not significantly change the body mass index (BMI), plasma glucose and lipid levels, or inflammatory markers in the blood. Reduced lowered systolic and diastolic blood pressure values were detected, regardless of food matrix or baseline values for blood pressure and BMI. In conclusion, our study showed that three-week consumption of the probiotic L. plantarum TENSIA either in cheese or yoghurt lowered diastolic and systolic blood pressure regardless of food matrix and baseline values of blood pressure and BMI, confirming the impact of the functional properties of the probiotic strain in decreasing CVD risk.

Kinetic oscillation stimulation as treatment of acute migraine: a randomized, controlled pilot study.

ObjectiveTo assess the relief of migraine pain, especially in the acute phase, by comparing active treatment, ie, kinetic oscillation stimulation (KOS) in the nasal cavity, with placebo.BackgroundExploratory trials testing the efficacy of KOS on migraine patients indicated that this treatment could be a fast-acting remedy for acute migraine pain.MethodThirty-six patients were randomized 1:1 using a placebo module to active or placebo treatment in this double-blinded parallel design study. Treatment was administered with a minimally invasive inflatable tip oscillating catheter. Symptom scores (0–10 visual analog scale) were obtained before treatment, every 5 minutes during treatment, at 15 minutes, 2, and 24 hours post-treatment, as well as daily (0–3 migraine pain scale) from 30 days pretreatment until Day 60 post. Thirty-five patients were evaluated (active n = 18, placebo n = 17). The primary end-point was the change in average pain score from before treatment to 15 minutes after treatment.ResultsPatients who received active treatment reported reduced pain, eg, average visual analog scale pain scores fell from 5.5 before treatment to 1.2 15 minutes after, while the corresponding scores for recipients of placebo fell from 4.9 to 3.9. The changes in pain scores differed between the 2 treatments by 3.3 points (95% confidence interval: 2.3, 4.4), P < .001. Already 5 minutes into the treatment, the difference (1.9 points) was significant (P = .007). The difference was likewise significant at 2 hours post-treatment (3.7 points, P < .001). One patient experienced an adverse event (a vasovagal reaction with full spontaneous recovery) during placebo treatment.ConclusionKOS is an effective and safe treatment for acute migraine pain.

CS-35 * TGF- INDUCES AND BMP SUPPRESSES VEGF RELEASE DEPENDING ON SMAD2/3 VERSUS SMAD1/5/8 SIGNALING IN GLIOBLASTOMA

The transforming growth factor (TGF)-β/bone morphogenetic protein (BMP) and vascular endothelial growth factor (VEGF) pathways have been attributed a major role in the pathogenesis in glioblastoma, but their interactions have remained poorly understood. Thus, we characterized TGF-β/BMP pathway activity in nine long-term glioma cell lines (LTC) and 4 glioma-initiating cell lines (GIC) in relation to constitutive and exogenous TGF-β/BMP-induced VEGF release. As reflected by TGF-β-induced SMAD2/3-phoshorylation and TGF-β/BMP-induced SMAD1/5/8 phosphorylation, glioma cells exhibit heterogeneous patterns of constitutive BMP/TGF-β pathway activation. Constitutive TGF-β pathway activity accounts for up to 69% of constitutive VEGF release which is positively regulated by SMAD2/3 and negatively by SMAD1/5/8 signaling in a cell line-specific manner. Exogenous TGF-β induces and exogenous BMP reduces VEGF release in most cell lines. Overall, TGF-β regulates VEGF release by glioma cells in an ALK-5-dependent manner involving SMAD2, SMAD3 and SMAD1/5/8 signaling. This crosstalk between the TGF-β and VEGF pathways may open up new avenues of biomarker-driven exploratory clinical trials. Beyond, BMP-dependent differentiation therapy as anti-glioma therapy may include VEGF-inhibitory effects.

Correcting for multiple-testing in multi-arm trials: is it necessary and is it done?

BackgroundMulti-arm trials enable the evaluation of multiple treatments within a single trial. They provide a way of substantially increasing the efficiency of the clinical development process. However, since multi-arm trials test multiple hypotheses, some regulators require that a statistical correction be made to control the chance of making a type-1 error (false-positive). Several conflicting viewpoints are expressed in the literature regarding the circumstances in which a multiple-testing correction should be used. In this article we discuss these conflicting viewpoints and review the frequency with which correction methods are currently used in practice.MethodsWe identified all multi-arm clinical trials published in 2012 by four major medical journals. Summary data on several aspects of the trial design were extracted, including whether the trial was exploratory or confirmatory, whether a multiple-testing correction was applied and, if one was used, what type it was.ResultsWe found that almost half (49%) of published multi-arm trials report using a multiple-testing correction. The percentage that corrected was higher for trials in which the experimental arms included multiple doses or regimens of the same treatments (67%). The percentage that corrected was higher in exploratory than confirmatory trials, although this is explained by a greater proportion of exploratory trials testing multiple doses and regimens of the same treatment.ConclusionsA sizeable proportion of published multi-arm trials do not correct for multiple-testing. Clearer guidance about whether multiple-testing correction is needed for multi-arm trials that test separate treatments against a common control group is required.Electronic supplementary materialThe online version of this article (doi:10.1186/1745-6215-15-364) contains supplementary material, which is available to authorized users.

Differential regulation of TGF-β-induced, ALK-5-mediated VEGF release by SMAD2/3 versus SMAD1/5/8 signaling in glioblastoma.

The transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF) pathways have a major role in the pathogenesis of glioblastoma, notably immunosuppression, migration, and angiogenesis, but their interactions have remained poorly understood. We characterized TGF-β pathway activity in 9 long-term glioma cell lines (LTCs) and 4 glioma-initiating cell lines (GICs) in relation to constitutive and exogenous TGF-β-induced VEGF release. Results were validated using The Cancer Genome Atlas transcriptomics data. Glioma cells exhibit heterogeneous patterns of constitutive TGF-β pathway activation reflected by phosphorylation not only of SMAD2 and SMAD3 but also of SMAD1/5/8. Constitutive TGF-β pathway activity depends on the type I TGF-β receptor, ALK-5, and accounts for up to 69% of constitutive VEGF release, which is positively regulated by SMAD2/3 and negatively regulated by SMAD1/5/8 signaling in a cell line-specific manner. Exogenous TGF-β induces VEGF release in most cell lines in a SMAD- and ALK-5-dependent manner. There is no correlation between the fold induction of VEGF secretion induced by TGF-β compared with hypoxia. The role of SMAD5 signaling is highly context and cell-line dependent with a VEGF inhibitory effect at low TGF-β and pSMAD2 levels and a stimulatory effect when TGF-β is abundant. TGF-β regulates VEGF release by glioma cells in an ALK-5-dependent manner involving SMAD2, SMAD3, and SMAD1/5/8 signaling. This crosstalk between the TGF-β and VEGF pathways may open up new avenues of biomarker-driven exploratory clinical trials focusing on the microenvironment in glioblastoma.

An Autologous Tissue Implant, NeoCart, for Treatment of Hyaline Cartilage Injury in the Knee

NeoCart is an autologous cartilage tissue–engineered implant designed for use in repair of articular cartilage injuries. It uniquely combines a type I bovine-derived collagen scaffold with autogenous chondrocytes and bioreactor treatment. It is currently in the third phase of an investigational study in the United States for treatment of symptomatic articular cartilage lesions of the distal femur. This multicenter, prospective, randomized controlled trial directly compares changes of multiple patient-reported outcome measures over 3 years with a control group undergoing microfracture surgery. This article describes the study design and indications for enrollment in the phase III trial. The technical elements of NeoCart culture and production process, surgical implantation procedure, and rehabilitation guidelines are outlined. In addition, we review previously published findings from the completed phase I safety and phase II exploratory trials.

Adaptive Design: Results of 2012 Survey on Perception and Use.

Adaptive designs are increasingly used in clinical trials. The Drug Information Association's Adaptive Design Scientific Working Group (ADSWG) works to foster collaboration among regulatory agencies, academia, and pharmaceutical and biotech companies to further the science of adaptive clinical development. The ADSWG Survey Subteam has collected data on the usage of adaptive designs in clinical research from multiple sources, including a recent ADSWG survey regarding the perception and usage of adaptive designs in academia and industry for studies between 2008 and 2011, as well as barriers to usage; a literature review examining publications of adaptive design methodology and usage between 2000 and 2011; and a trial registry review of adaptive design references from 1996 to 2011. The comprehensive results of the ADSWG 2012 survey are provided in this article with comparisons to our previous 2008 survey, the literature and registry reviews, and recent surveys carried out by the US Food and Drug Administration (FDA) and the European Medicines Agency. Results of the ADSWG 2012 survey illustrate that industry and academia are showing more enthusiasm for adaptive trials, accompanied by an increase in the number of trials using designs described as less well understood in the FDA draft guidance on adaptive designs, published in 2010. The increased use of these methods in exploratory trials is consistent with the FDA draft guidance. The survey also identified several examples of successful marketing applications supported by confirmatory trials utilizing adaptive designs that were considered, at least at the time of the draft guidance, as less well understood. While some of the technological barriers to adaptive design usage identified in the 2008 survey are now less common, there are several important persistent barriers to usage. Organizations can help overcome these barriers through education, preplanning, and early engagement in discussions with the regulators.

Academic Clinical Trials and Drug Regulations in Japan: Impacts of Introducing the Investigational New Drug System

In Japan, academic clinical trials do not generally need to be conducted under good clinical practice and cannot therefore be used for regulatory submission for marketing authorization of new medical products. We reviewed 2 differential regulatory systems governing clinical trials in Japan and the development histories of 2 case products whose clinical trials at the early development stage were conducted by academic researchers and transferred to the private sector for further development toward commercialization in Japan. We further estimated that the introduction of the investigational new drug system may have accelerated the development of tocilizumab, an antibody drug for rheumatoid arthritis, at best by 2 years by utilizing the results of early exploratory clinical trials conducted by academic investigators. Similarly, an enlarged indication for JACE®, a cultured epithelium autograft for severe burns, would have been expected at launch by utilizing the results of academic trials investigating various indications. These possible impacts and estimations would warrant introducing the investigational new drug system into Japan drug regulatory system.

Indigenous Community Health and Climate Change: Integrating Biophysical and Social Science Indicators

This article describes a pilot study evaluating the sensitivity of Indigenous community health to climate change impacts on Salish Sea shorelines (Washington State, United States and British Columbia, Canada). Current climate change assessments omit key community health concerns, which are vital to successful adaptation plans, particularly for Indigenous communities. Descriptive scaling techniques, employed in facilitated workshops with two Indigenous communities, tested the efficacy of ranking six key indicators of community health in relation to projected impacts to shellfish habitat and shoreline archaeological sites stemming from changes in the biophysical environment. Findings demonstrate that: when shellfish habitat and archaeological resources are impacted, so is Indigenous community health; not all community health indicators are equally impacted; and, the community health indicators of highest concern are not necessarily the same indicators most likely to be impacted. Based on the findings and feedback from community participants, exploratory trials were successful; Indigenous-specific health indicators may be useful to Indigenous communities who are assessing climate change sensitivities and creating adaptation plans.

Alternative strategies for proof-of-principle studies of antibacterial agents.

The proof that a new antibacterial agent is not only active in vitro but also effective in vivo under clinically relevant conditions is currently provided (i) by using appropriate nonclinical models of infection and pharmacokinetic-pharmacodynamic (PK-PD) analysis providing evidence of the likelihood of clinical efficacy and (ii) by examining the study drug in exploratory clinical trials, as well as dose and schedule finding during phase II of clinical development. This approach is both time-consuming and costly. Furthermore, PK-PD targets for any novel antibacterial agent cannot be derived from studies with experimental animals. Therefore, alternative strategies have to be identified to prove the principle that a novel antibacterial agent is active under clinically relevant conditions. This review summarizes evidence that the quantitative analysis of shifts in the viable counts of pathogens in infected patients or the evaluation of the PD effect of an investigational agent on indicator organisms of the human resident microflora or colonizers of healthy volunteers, if paralleled with PK monitoring of serum and the target site, provides an alternative to a classical proof-of-principle study in the course of a phase II study program.

Sugar Beet: A Historical Perspective in Indian Context

Sugarbeet (Beta vulgaris L.) was introduced in India in 1950s. Exploratory trials for root and seed crop were carried out by Indian Institute of Sugarcane Research, Lucknow, India all over the country and suitable sites were identified. It was observed that sugarbeet could be grown in the rabi season in the plains of north India for its roots which contain 13–15 % sugar; and the seed crop could be grown in the hills above an altitude of 5,000′. An All India Coordinated Project was launched by the ICAR in 1971 to carry out multi-location research on sugarbeet and concurrent with this was the establishment of a sugarcane-cum-sugarbeet sugar factory at Sriganganagar in Rajasthan. The project and the factory were operational for nearly three decades and the crop was well established in that area. However, there was no expansion in the area as no new sugar factory with the additional machinery required to process sugarbeet came up. The situation has been confounded by no government policy of incentive for setting up a washing, slicing and diffusion plant in the existing sugarcane factories. The current scenario is no different except that there are now openings for production of ethanol from sugarbeet. The Indian Sugar Industry is getting sensitized to the feasibility of sugarbeet cultivation. The reason for sugarbeet not picking up commercially is mainly the lack of market. Since it is an industrial crop, no seed money or incentives have been given to the sugar industry for installing the additional machinery. The work done at IISR along with other partners from time to time (such as GBPAUT, RAU, YSPUFH, BCKVV, MPKVV, VSI, etc.), has left no doubt about the agricultural feasibility of sugarbeet in the country. Varieties, machines, agronomy and plant protection technologies have been developed for growing sugarbeet in the subtropical and tropical India. The IISR is actively involved in sugarbeet germplasm maintenance and limited seed production at its breeding outpost at IVRI, Mukteswar since 1976. India stands to gain from capitalizing on the potential of sugarbeet for sugar, ethanol and fodder. It offers to enhance the livelihood options of hill farmers by growing the required sugarbeet seed in India. Sugarbeet being a halophyte can bring under cultivation a large area afflicted with salinity in the country.

Malignant melanoma in early‐treated Parkinson's disease: The NET‐PD trial

The risk for malignant melanoma is higher than expected in Parkinson's disease (PD). The National Institutes of Health (NIH) Exploratory Trials in PD (NET-PD) Long-term Study 1 (LS-1) trial is a contemporary phase 3 study of subjects with early, treated PD. The objective of this work was to assess the incidence of malignant melanoma in a PD cohort. Incident melanoma cases were identified from the adverse events log. The expected number of cases was calculated, using the expected incidence rates and the number of person-years. A total of 618 females and 1119 males were followed for 6452 person-years; 19 new melanoma cases were observed. The expected number was 5.29. The standardized event ratio compared to the general population was 3.6 (95% confidence interval, 2.2-5.6). The risk for developing melanoma was higher than expected in the NET-PD LS-1 cohort and was similar to the risk reported in earlier comparable clinical trial cohorts. Dermatologic screening may be useful in Parkinson's disease to identify melanoma at an early stage.

Extending zygonic theory to analyse patterns of musical influence between children creating pieces of music in groups, in England and Japan

This article reports on initial exploratory trials of a methodological extension of zygonic theory, through which this psychomusicologically-based approach was used to analyse patterns of musical influence within pieces created by groups of primary school children aged 9–11 years in England and Japan. Previously, the theory had been used in educational and therapeutic contexts to gauge the musical impact of each participant on the other in one-to-one musical interactions. The preliminary findings reported here suggest that zygonically-derived analytical techniques may potentially be of value not only in defining children’s musical contributions and patterns of influence as they seek to create pieces in groups, but also in comparative studies that examine the potentially dissimilar improvisatory approaches adopted by different cohorts of pupils. It is further argued that zygonic measures of musical influence may be of value as inverse proxy measures of creativity.

Bio-distribution study of Reolysin® (pelareorep) through a single intravenous infusion in Sprague-Dawley rats

Numerous pre-clinical and clinical studies on reovirus have generated valuable information which supports the use of this orphan virus as an investigational drug for cancer treatment. Reolysin® (pelareorep) is a clinical formulation of the human Reovirus Type 3 Dearing strain. The clinical safety and efficacy of Reolysin® in humans is being tested on an assortment of cancer indications as a mono and/or combination therapy. Reovirus has many inherent characteristics that make it a potential candidate for virotherapy, including: the rapid and natural spread through the haematogenous route, the ability to overcome immunological barriers thereby reaching tumor sites, and being replication-competent. The purpose of this study was to elucidate the bio-distribution pattern of Reolysin® in healthy Sprague-Dawley rats. Following a single 15-min intravenous infusion via the tail vein in Sprague-Dawley rats, the levels of virus genome were determined in 16 organs/tissues by RT-qPCR (Reverse Transcriptase- Quantitative Polymerase Chain Reaction) over a 336 h (Day 15) incubation regime. Consistent with previous studies, maximal reovirus RNA levels were observed in the spleen; indicating its involvement in viral uptake and clearance, followed by heart, ovaries, tail (infusion site), liver and lungs. All the organs/tissues demonstrated unquantifiable levels of reovirus genome at the end of incubation, suggesting substantial to complete viral clearance. Several studies in the last decade have described the use of reovirus for treating ovarian cancers. An increase of reovirus genome in ovaries at 24 h post infection was noted. The results will aid in the design of additional exploratory clinical trials for Reolysin®.

Active post-marketing surveillance of the intralesional administration of human recombinant epidermal growth factor in diabetic foot ulcers

BackgroundAfter several exploratory and confirmatory clinical trials, the intralesional administration of human recombinant epidermal growth factor (hrEGF) has been approved for the treatment of advanced diabetic foot ulcers (DFU). The aim of this work was to evaluate the effectiveness and safety of this procedure in medical practice.MethodsA prospective, post-marketing active pharmacosurveillance was conducted in 41 hospitals and 19 primary care polyclinics. Patients with DFU received hrEGF, 25 or 75 μg, intralesionally 3 times per week until complete granulation of the ulcer or 8 weeks maximum, adjuvant to standard wound care. Outcomes measured were complete granulation, amputations, and adverse events (AE) during treatment; complete lesion re-epithelization and relapses in follow-up (median: 1.2; maximum 4.2 years).ResultsThe study included 1788 patients with 1835 DFU (81% Wagner’s grades 3 or 4; 43% ischemic) treated from May 2007 to April 2010. Complete granulation was observed in 76% of the ulcers in 5 weeks (median). Ulcer non-ischemic etiology (OR: 3.6; 95% CI: 2.8-4.7) and age (1.02; 1.01-1.03, for each younger year) were the main variables with influence on this outcome. During treatment, 220 (12%) amputations (171 major) were required in 214 patients, mostly in ischemic or Wagner’s grade 3 to 5 ulcers. Re-epithelization was documented in 61% of the 1659 followed-up cases; 5% relapsed per year. AE (4171) were reported in 47% of the subjects. Mild or moderate local pain and burning sensation, shivering and chills, were 87% of the events. Serious events, not related to treatment, occurred in 1.7% of the patients.ConclusionsThe favorable benefit/risk balance, confirms the beneficial clinical profile of intralesional hrEGF in the treatment of DFUs.

Low triiodothyronine: a pathway to coronary calcification in patients maintained on peritoneal dialysis

Low triiodothyronine: a pathway to coronary calcification in patients maintained on peritoneal dialysis

Research Today

Basic research has identified the 2 major defects linked to polycystic disease: (i) the cystic cells proliferate excessively; (ii) these cells secrete fluid that enlarges the cysts. The main therapeutic strategies in autosomal dominant polycystic kidney disease (ADPKD) are the use of drugs capable of interfering with the mechanisms causing these defects. One of the strategies explored was the inhibition of the mTOR system. Unfortunately, 2 clinical trials have failed to show a protective effect of this class of drugs. Somatostatin is another molecule under intense clinical validation. At the moment, the collected data suggest a possible activity against ADPKD, but the results are still too preliminary to attain clinically meaningful conclusions. Tolvaptan is a vasopressin receptor antagonist that has been extensively studied: a clinical trial recruiting an adequate population suggested a possible positive effect of this molecule in the reduction of renal volume growth and the achievement of significant clinical targets. The near future promises new exploratory clinical trials of molecules that have already been assessed in the recent past or of completely new therapeutic strategies. For the high number of enrolled patients, the HALT study attracts the attention of the scientific community. This trial will explore the role of antagonists of the renin-angiontensin system in slowing the progression of ADPKD. Finally, a category of drugs previously unexplored is that of the inhibitors of the epidermal growth factor receptor. Clinical research in ADPKD is extraordinarily active in this period and this consideration allows a cautious optimism about the prospective therapies for this disease that for long remained orphan. A shadow on the prospect of future results in clinical research in this field comes from the observation that a considerable number of trials show a methodologically inadequate design.