Clinical Trials and Practice – Open Journal
Editor- In-Chief: Li M. Wen, MD, MMed, PhD Title proper: Clinical Trials and Practice – Open Journal Subject: Clinical Trials Publisher: Openventio Publishers Dates of publication: 2017 Frequency & Medium: Half- Yearly , Online Language: English Country: India Indexed by: CROSSREF , ROAD , THE KEEPERS Title DOI of the Journal: http://doi.org/10.17140/issn.2771-7380
Digital Therapeutics and Decentralized Clinical Trials Optimization in an Era of Increasing Complexities
Clinical trials typically revolve around three models: traditional, virtual, and decentralized trials. In traditional clinical research, data collection and data capture happen onsite. Virtual trials are fully remote (i.e., remote monitoring) where enrollment happens at a distance. Moreover, Decentralized trials happen when both the data collection and data capture occur outside of the traditional site.According to Naveen Dha in “What is a Decentralized Clinical Trial (DCT),” DCT can “either be fully remote or adopt a hybrid approach where some physical-site attendance is required. They are achieved with the use of remote monitoring and diagnostics, home health providers, local labs, digital capture of consent data, and direct-to-patient drug distribution. The purpose of these types of studies is to reduce or completely eliminate the requirement of face-to-face interactions between researchers and participants”.
Practical Pointers for Drug Development and Medical Affairs
It is absolutely an essential part of the clinical research process in providing informed consent, and having the potential participant sign the forms (ICF).1 It may help foster enrollment by also explaining to potential study participants not only why the research is being conducted, but also how their individual participation will help in product development and what this product has the potential to accomplish. • It is more difficult than ever to enroll patients in Phase I oncology clinical trials.2 One partial solution, when feasible, is to make this a multi-center semi-decentralized clinical trial rather than one inhouse unit.
Patient and Surgeon’s Concerns with Post-Mastectomy Nipple Reconstruction: An Alternative to Traditional Nipple Reconstruction
Aims The aim of this paper is to determine what women who undergo reconstructive surgery after mastectomy (due to breast cancer) are seeking. It also answers the question, how plastic surgeons are attempting to fill this need. Methods A survey was undertaken of 84 plastic surgeons and 70 of their patients who underwent recent mastectomy and reconstruction surgery. All the material was deidentified before analysis. Results The majority of the women wanted their breasts and nipples to be natural and have the same appearance (or sometimes to be more attractive) or similar appearance. Conclusion Women undergoing this type of surgery frequently develop a decreased quality-of-life (QoL) which also affects their feeling of femininity, sexuality, and psychological well-being. The post-surgery time period and the additional necessary treatments are extremely stressful events. The importance of their breast post-operative aesthetics correlated with their self-esteem and body image. It is important for plastic surgeons to take these factors into consideration, when planning their reconstructive surgery.
The Importance of an Unbiased Safety Review Board in Phase I Clinical Trials
Conducting clinical trials is the process that biopharmaceutical companies must use to demonstrate that their product is safe, well-tolerated, and efficacious to obtain marketing approval from the Food and Drug Administration (FDA).1 Human clinical trials are initiated after preclinical trials have demonstrated sufficient safety data. At that point, the FDA will allow these trials to begin on normal healthy volunteers. However, if the FDA considers the risks too high for these volunteers, the agency will require the specific disease population to be studied. For example, the associated adverse effects of many oncology drugs frequently place them into a riskier category, and ethically it would be inappropriate to expose healthy volunteers to these medications. Since many adverse effects of a drug are not yet known during a Phase I study, they carry an inherent risk to the participants.
Combat Pandemic: Coronavirus Disease-2019 Vaccines Production, Clinical Trials and Global Partnerships
The advent of coronavirus disease-2019 (COVID-19), in March 2020, has forced the entire world into continuously changing dimensions, the emergence of variants has put forward a challenge to scientists and doctors, indeed the entire world to cope with it. A lot of clinical research was done, starting with the use of Chloroquine, an anti-malarial drug to treat COVID-19, antivirals and indeed entire world experienced havoc and a death toll due to the coronavirus which led to the emergence of various vaccine platforms developed against changing variants of coronavirus and in this pandemic messenger Ribonucleic acid (mRNA) and nanotechnology added new dimensions to vaccine development. Vaccines may induce additional cellular or humoral immune regulations, including The cell (helper T-cell) responses and germinal center responses, and form relevant memory cells, which in turn enhance their efficiency. As the benefit outweighs the safety issues with vaccination so far, the World Health Organization (WHO), has approved a total of ten vaccines, to use in emergencies, including 3 Indian vaccines (Covovax™, Covaxin® and Sputnik V). The first part, of this mini-review highlights vaccine production, and the clinical trials landscape, and the second part discusses the emergence of global partnerships, and the equity of vaccines to all, taken together, combating pandemics.
Potential Errors and Corrections in Early Phase Drug Development
Many foreign and small companies trying to enter the United States biopharmaceutical market make avoidable errors in their early clinical phase drug development and clinical trials. They need to first understand the risks that they must endure with patent law, regulatory hurdles, the complexity and duration of the necessary clinical trials, and the large cost of drug development, which often necessitates raising substantial capital from investors. If appropriate capital for these clinical studies must be raised, then the company must be able to clearly articulate a realistic expected return on investment to these individuals. So, they must also understand the market, its exclusivity, and the competition. This must all be put together in a sleek pitch deck. Early errors frequently begin with too few, inadequate, or poorly constructed patents. These and other risks and errors may be prevented by the use of an experienced product development team. Many of these errors could be avoided if companies used more experienced drug development professionals to assist them in selecting the optimum patent strategy, regulatory plan, budget, contract research organization (CRO), clinical investigators, and etc. It is hoped that this opinion piece will help make early clinical trials more effective and save time and money.
Design and Statistical Methods for Handling Covariates Imbalance in Randomized Controlled Clinical Trials: Dilemmas Resolved
Introduction In practice, between groups baseline imbalance following randomization not only opens effect estimate to bias in controlled trials, it also has certain ethical consequences. Both design and statistical approaches to ensure balanced treatment groups in prognostic factors are not without their drawbacks. This article identified potential limitations associated with design and statistical approaches for handling covariate imbalance in randomized controlled clinical trials (RCTs) and proffered solutions to them. Methods A careful review of literatures coupled with a robust appraisal of statistical models of methods involved in a way that compared their strength and weaknesses in trial environments, was adopted. Results Stratification breaks down in small sample size trials and may not accommodate more than two stratification factors in practice. On the other hand, minimization that balances for multiple prognostic factors even in small trials is not a pure random procedure and in addition, could present with complexities in computations. Overall, either minimization or stratification factors should be included in the model for statistical adjustment. Statistically, estimate of effect by change score analysis (CSA) is susceptible to direction and magnitude of imbalance. Only analysis of covariance (ANCOVA) yields unbiased effect estimate in all trial scenarios including situations with baseline imbalance in known and unknown prognostic covariates. Conclusion Design methods for balancing covariates between groups are not without their limitations. Both direction and size of baseline imbalance also have profound consequence on effect estimate by CSA. Only ANCOVA yields unbiased treatment effect and is recommended at all trial scenarios, whether or not between groups covariate imbalance matters.
The Case for Digital Pill Use in Clinical Trials
Medication adherence in clinical trials is significantly overestimated through every phase of drug development. This can cause a reduction in statistical power, potentially resulting in incorrect conclusions regarding efficacy, safety, tolerability, and dose-response relationships, in addition to major cost overruns. Digital pill systems enable adherence measurement through an embedded ingestible sensor paired with an external receiver. An oral pharmaceutical product is over-encapsulated by a pharmaceutical-grade shell containing a biocompatible sensor. Upon exposure to gastrointestinal fluid, the shell dissolves and the sensor is activated. Medication ingestion data is transmitted via a digital signal. Clinicians and researchers use this data to track, in real time, when and if a medication was taken. These systems have demonstrated a 99.4% rate of accuracy, and have over 15-years of supporting experience and safety data. Spurred by the accelerated adoption of technology in healthcare and in everyday life, patients have become tech-savvy. They quickly adapt to these devices, and are able to use them safely and effectively. Digital pills can be implemented in most types of studies. In early-stage trials such as pharmacokinetic and pharmacodynamic studies, or dose-finding studies, accurate information on maximum-tolerated dose levels is essential and cannot be established unless study participants are highly adherent. In later-stage pivotal trials, effective medication adherence tracking can strengthen the dataset and confidence in the study results. Significant nonadherence may generate results that do not meet statistical or clinical significance for the critical endpoints, resulting in at worst, a failed trial, or at best, the need to enroll additional patients at substantial additional cost. Most clinical trials fail to achieve statistical significance, and poor medication adherence is often an important contributor. A digital pill system can ensure the quality and integrity of adherence data, increase confidence in the overall study data, and improve clinical trial efficiency.
The Importance of Teaching and Fostering Clinical Research in Primary Health Care
It is important for primary health care (PHC) teaching institutions and hospitals to create an atmosphere fostering clinical investigation for all health care practitioners (HCP).1 This involves not just clinical trials, but observations, examinations, and investigations are a critical part of the education of any health science students.2 This is the basis of science. Without knowing how to apply a scientific thought process and methodology to a clinical situation, it will prevent one from reaching their optimum abilities. Easy-to-conduct, practical single subject studies also known as N-1 clinical trials, can help lead to modifying a patient’s therapy, new practice patterns, therapeutic improvements, and increasing students skills.3 These single subject studies (N-1) are multiple cross-over trials involving the same single patient. Implementing clinical investigations into HCPs work routine, can make them more passionate about their work, prevent burnout, and lead to new products and services.
Coronavirus Disease-2019 Clinical Trial Case Studies Within the Biotechnology and Clinical Research Organizations Industry
On March 11th, 2020 the World Health Organization (WHO) declared the novel coronavirus disease-2019 (COVID-19) outbreak a global pandemic. Coronaviruses are non-segmented positive-sense ribonucleic acid (RNA) viruses in the Coronaviridae family, which typically affects the respiratory, gastrointestinal, hepatic and neurologic systems. Under Food and Drug Administration (FDA) expanded access programs and federal emergency guidelines, COVID-19 clinical trials have been some of the most successful trials to date. However, significant challenges have been presented for both Clinical Research Organizations (CROs) and the sponsoring companies, as a result of the COVID-19 pandemic.
The Promise of Small Data for Telemedicine in Chronic Condition Management: A Real-World Case Series
Connected care is defined as the “real-time, electronic communication between a patient and a provider, including telehealth, remote patient monitoring, and secure email communication between clinicians and their patients” (Alliance of Connected Care). Connected care can create a high-value interaction strategy with patients when it makes thoughtful use of commercially available digital health technologies with demonstrated both clinical and economic effectiveness. Karantis360™, is a home sensor technology that enables real-time tracking, data analytics and predictive care for personal (at home) care powered by IBM Watson Health. IndividuALLyticsTM is a telemedicine platform driven by a patent-pending an N-of-1 analytical engine and related digital dashboards that provides individual, patient-level evaluation of treatment response. The underlying technology combines disparate digital health technology data with the best evidence-base guidelines with N-of-1 methodology. The output allows for creation of personalized treatments empirically tested at the patient-level over time (aka over the course of care). When aggregated both within and across persons, the time-ordered data can build predictive pathways of behavior and ensure the relevant care and medical treatments are in place to support effective medical and self-management of chronic illness. This case-series report describes the implementation of a joint home sensor technology (big data) and an N-of-1 analytic engine (small data) with three elderly consented volunteer customers- patients of Karantis360™. Each person underwent successive, 2-week behavioral change treatment phases to determine usability, utility regarding medical and self-management and any proximal effects on health risks.
Role of Low-Level Laser Therapy as an Adjunct in the Management of Diabetic Ulcer
Diabetes mellitus (DM) is a chronic debilitating condition affecting people worldwide and diabetic foot ulcers are also a common problem. The treatment of diabetic ulcers requires a multimodal approach. Adjuvant low-level laser therapy (LLLT) may be useful in lesions with protracted healing course but the evidence is still limited. In this study, we share our experience regarding the use of low-level laser therapy as an adjuvant treatment modality in a patient with diabetic foot ulcer.
The Role of Negative Pressure Wound Therapy with Instillation and Dwell Time in the Preparation of Wound Bed
Introduction Although the negative pressure wound therapy (NPWT) is a time tested method of wound preparation, the role of NPWT with instillation and dwell time (NPWTi-d) in decreasing the downtime of wound preparation needs to be evaluated. Objective The objective of this study is assess the role of NPWTi-d in wound bed preparation. Materials and Methods This study was conducted in a tertiary care center, after getting informed consent and ethical clearance. NPWTi-d was done on a 36-years-old female with no known co-morbidities admitted with infected raw area over the right below knee amputation stump and exposed bone who was not responding well to conventional wound dressing. NPWT was applied with the help of sterile polyurethane sponge and two tubes. The antimicrobial solution used was ionic silver solution, just enough to wet the sponge completely and up to the point when the transparent occlusive covering begins to lift. Negative pressure was applied at 125 mmHg. The wound was bathed with ionic silver solution and it was allowed to stay in the wound for 10-minutes, after every 2-hours of negative pressure application. This was continued for 1-week. The dressing was opened at the end of 1-week, wound irrigated with normal saline, exudate swabs for culture taken and debrided, following which fresh NPWTi-d was applied. This was repeated for the next 3-weeks. Result By the end of third week, the wound became clean, fully covered with healthy granulation and the wound bed was ready to undergo the definitive wound cover procedure.
Negative pressure wound therapy with instillation dwell time (NPWTi-d)
How a Network Came Together to Manage a Large Research Program During the Pandemic
Hackensack Meridian Health, a large New Jersey network comprised of 17 hospitals, a medical school, and 200 ambulatory care centers, executes a large research program with approximately 1000 active human subjects studies. With the arrival of the coronavirus disease-2019 (COVID-19) pandemic, the Office of Research Administration was confronted with a series of challenges. These included minimizing face-to-face contact among research participants and staff, allocating limited resources to handle the influx of COVID-19 related proposals, providing human subjects protection training to the physicians and staff who were needed to run the clinical trials, adjusting bio-repository activities to meet the increased demand for samples, and disseminating all of the new regulatory and operational information to the thousands of researchers in the network. The network’s success in modifying its research program quickly and effectively to adapt to the changing landscape can be attributed, in large part, to the centralized nature of the research administration.
Innovation in Clinical Trials is Possible: The Hidden Opportunity in the Coronavirus Disease-2019 Emergency
The coronavirus disease-2019 (COVID-19) emergency has clearly shown the need to discover, test and produce a new vaccine but also in general the fragility of the current chain of clinical trials. Through this emergency, is it possible to look at the current clinical trial processes with new eyes? Is it possible to seize the opportunity for change and to have confidence in the possibility of their improvement? In this short article the authors wanted to give an optimistic answer to this question by pushing on the possibilities of innovation nowadays.
Diversity and Recruitment of Minorities in Clinical Trials: An Unmet Need
Patient centricity has led to the idea that drugs should answer medical needs not only defined by the medical bodies but relevant for the patients themselves. This implies that the diversity of the patients should be represented in clinical trials. Disparities in representation of diverse populations in clinical trials have been well-documented for several pathologies like arterial hypertension, diabetes but also in oncology. Today, Caucasian patients included in clinical trials represent at least 75% of the clinical trials population even in pathologies where minorities are largely more affected than Caucasians. Filling the gap in diversity is an important matter to ensure ethics, good practices, regulatory compliance, patient safety and scientific validity. To achieve their recruitment goals and being patient centric, sponsors and investigational sites need to pay attention of this problem and put in place specific strategies. Mistrust of patients of minority groups toward clinical research is one of the main barriers along with lack of access to clinical trials (low awareness, communication barriers, distance to investigational sites). Adapted communication, community-based strategies are some of the useful strategies directed to the patients. Investigators may not encounter diverse populations in their area or may not be aware of unconscious bias when identifying patients suitable for a clinical trial. Looking for referrals and raising awareness of the risk of bias with training on culturally sounded approaches could help investigators to recruit more diverse populations. Lack of awareness and costs may prevent sponsors to focus on diversity but ethics, benefits of data acquisition and patient centricity should be enough motivators to modify this trend. Patients, investigators and sponsors have their own barriers to tackle the lack of diversity in clinical trials. The cultural background of all stakeholders is an important factor in those barriers. Only multidisciplinary approaches including human sciences would help to define patient recruitment strategies that would mitigate the current lack of diversity.
The Digital Stethoscope in Telemedicine: A Health Camp Study
India is a vast country with limited human resources. People living in remote areas often have limited access to healthcare facilities. To address this need and to increase healthcare awareness, health camps have been established. These camps are often supervised by junior physicians. Telemedicine, and in particular use of a digital stethoscope may provide better diagnosis and better consultation to the patient by senior physicians located remotely. This article highlights the clinical use of a digital stethoscope in such a health camp.
Beyond Placebo: Alternative Options to the Randomized Control Trial Design in Rare Disease Studies
Unique difficulties and challenges can arise for rare diseases and orphan disease indications within a clinical trial. Some of the challenges encountered by trials that are working on rare diseases can include recruitment and enrollment. One of the explanations for the challenges that are encountered in rare disease trials is because of the trial design of study, where the investigational product is being compared to the placebo. This review paper discusses the usage of placebo and when other options could be taken into consideration while creating the protocol, specifically with consideration to rare disease studies. It is essential for the investigators and those designing the protocol to consider alternative options from the standard randomized controlled trial. The aim of this paper is to review alternative trial design options. The trial designs discussed in this review paper include crossover trials, single arm studies and historical data, and n-of-1 trials.
Recruitment in clinical research trials can be challenging in trials that are time-sensitive and/or are rare disease and critical care trials. One of the hurdles for recruitment in these types of clinical trials is due to the consent process, and the need to have consent of the patient within a certain timeframe, or the patient unable to consent for themselves. This paper will discuss the usage of the utilization of remote consent options for these trials.
Role of Bactiguard Infection Technology in Preventing Catheter-Associated Urinary Tract Infections
To study the role of bactiguard infection technology (BIP) in preventing Catheter-associated urinary tract infections. This study was conducted in a tertiary care centre in the Department of Plastic Surgery, JIPMER, Pondicherry, India in the month of August 2019. The study subject was a 55-year-old gentleman with Fournier’s gangrene and type 2 diabetes mellitus (DM). The Foley’s catheter with BIP technology was used and its role in preventing urinary tract infections (UTI) was studied over a period of 10-days. During the period of the catheter use in our subject, patient did not develop features of urinary tract infections. BIP technology is claimed to be effective in preventing Catheter-associated urinary tract infections but further studies in more individuals is required to validate the same.
Catheter associated urinary tract infection (CAUTI)
Clinical Research: The Future of Medicine Stuck in the Digital Past
The past eight years I’ve spent working at clinical research sites have been gratifying in countless ways. From seeing direct patient improvement as a result of their involvement in a trial to learning about Food and Drug Administration (FDA) approval of a therapy on which we’ve conducted trials, the observable outcomes of contributing to the forefront of scientific knowledge are continuously rewarding. However, despite tangible medical field advances, day-to-day operations are often performed in an antiquated fashion. In this article, I highlight four outdated and inefficient methods still utilized in common clinical trial operations and offer suggestions for updated digital replacements.
Role of Sound Enhancer Device in Teleconsultation
Aim To study the role of sound enhancer device in teleconsultation. Methods This study was conducted in the plastic surgery department in a tertiary care centre in the month of May-June 2019. A sound enhancer device was used with mobile phone for videoconferencing as form of teleconsultation by plastic surgery trainees in operation theatre and outpatient department. At the end of the study feedbacks were taken from the trainees. Results It was found that on using the sound enhancer device, the sound quality improved and it was helpful in the teleconsultation sessions using videoconferencing. Conclusion The use of sound enhancer is a simple, cost-effective, innovative method of using a simple technology to aid in utilisation of teleconsultation facilities in a very non-sophisticated way.
Latest Results from Immunotherapy Clinical Trials in Triple Negative Breast Cancer
Cancer immunotherapy has evolved enormously in the recent years with better understanding of immune reactions, immune microenvironment and immunosurveillance. Breast cancer is characterized by large heterogeneity, a fact which rather complicated the development and the approval of novel therapeutic options in comparison to the majority of other solid tumors since each subtype has required a unique scientific approach and different targets and goals. Triple negative breast cancer (TNBC) is considered the most aggressive of the breast cancer subtypes with limited treatment options and worse outcome compared to others. This article summarizes some of the early clinical studies and the recently presented phase III clinical study of immunotherapy checkpoint inhibitors in this difficult setting.
The Effectiveness of Transcutaneous Electrical Nerve Stimulation Versus Carbamazepine in Trigeminal Neuralgia: A Randomized Controlled Trial
To determine if the treatment of refractory trigeminal neuralgia (TN) with transcutaneous electrical nerve stimulation (TENS) could lead to improved pain control. Materials and Methods We enrolled 20 patients with refractory TN in a double blinded, randomized, placebo-controlled clinical trial. Patients received either TENS for group 1 (n=10) or carbamazepine (CBZ) for group 2 (n=10). The visual analog pain scale (VAS) and the barrow neurological institute (BNI) pain scale, the number and duration of pain episodes and daily analgesic intake were analyzed for each group at 1 month, 2 months, 3 months, 1 year, 3 years and 5 years. Results The TENS group achieved better pain control than the CBZ group (p<0.05). Pain-free patients accounted for 60% in the TENS group and 50% in the CBZ group 1 month after initiating treatment, 100% and 77.77% at 3 months, 100% and 62.5% at 1 year, 100% and 50% at 3 years, respectively. The TENS group remained pain free for 3 years. At the 5-year mark, all members of the TENS group and the CBZ group presented pain recurrence. Conclusion TENS group scored significantly lower in pain scales compared with the CBZ group. TENS group was pain free for a longer period of time compared with the CBZ group. Significant differences between both groups favored TENS therapy, however the small sample size remains an important limitation of this study.
Transcutaneous electrical nerve stimulation (TENS)
Cluster Randomized Controlled Trials: A Quick Update on Concepts and Types
Cluster randomized controlled trials have certain complexities both at design and statistical analysis stages of the experiment. Although, this experimental study approach offers solutions in situations where it would be inappropriate to randomize individuals into treatment arms its design and statistical analysis are not without certain unique challenges. Compared to individual randomized controlled trials, very limited understanding of the design concepts in cluster randomized controlled trials exists, this perhaps explain reasons it is not as popular as the former. This short note presents a quick description of cluster randomized controlled trials with a view to enhance capacity in its design, conduct and management. It will also provide students and researchers with ready-made information necessary to make appropriate choices regarding type of cluster randomized trials given a prevailing research environment.
Clinical Investigations on Medical Devices, after the New European Regulation (2017/745)
Medical devices (MDs) include different products and their importance in the healthcare industry is truly remarkable. The recently issued Regulation 2017/745 (Reg. 2017/745) introduced several major changes concerning planning, conducting and reporting of clinical investigations (CIs). Manufacturers and independent researchers would have to adapt quickly to this complex regulation, as the transition period from the previous regulations to the new one would last only three years. The present study having analysed Reg. 2017/745, provides a reference guide for researchers willing to conduct a CI. In particular, this study focused on six aspects of practical interest: (1) significance of CIs in the clinical evaluation of MDs, (2) aims of a CI, (3) cases where a CI is mandatory and exceptions to this rule, (4) application procedure for a CI, (5) requirements for conducting CI, (6) serious adverse events (AE) reporting (7), CI results. The regulations governing CI are influenced by different international, national and regional laws and guidelines. The aim of the paper is to create awareness among the readers about complex regulations and provide the readers a reference to the EU regulations. In addition to that, the authors stress on some issues that they consider to be of particular importance. Even though this paper does not serve as a substitute or replacement of the regulation; it acts as a guide for the reference of the readers with respect to the EU, national and local regulations. The authors conclude that the design and conducting of CIs demands that the personnel in charge have the relevant training and expertise in the field of MDs.
Distribution and Conduct of Clinical Trials Involving Music Therapy: Registered Clinical Trials in the Last 15 Years
Objective: This study aimed to conduct an evaluation of music therapy clinical trials worldwide, to understand what trials have been conducted and to show the chronological changes. Additionally, we sought to clarify issues related to providing clinical trial registration information. Methods: We searched the International Clinical Trials Registry Platform (ICTRP) database for “music therapy,” and identified the disease target for each article found. Results: A total of 150 clinical trial studies were found in the ICTRP using the term “music therapy.” In these trials, music therapy was used for improvement of social functioning in schizophrenia and/or serious mental disorders, anxiety and depressive symptoms, and cancer symptoms. Twenty-five clinical trials were actively recruiting. Sixteen of the 25 trials were registered in the United States at ClinicalTrials.gov, of which 9 trials were conducted in the US. Seven trials were conducted in other countries such as Spain, Taiwan, and China. Conclusion: A search for music therapy clinical trials retrieved 150 trials from the ICTRP, and the number of clinical trial registrations has increased yearly. Music therapy is widely used in patients with various diseases, including Alzheimer’s disease, anxiety, and arthritic pain and has the potential to improve certain disease outcomes, but there is not enough evidence to substantiate its efficacy. It is important to enlighten researchers and pharmaceutical companies on the proper management of the quality of such clinical trial information, as this is an important issue.
Model Based vs. Rule Based Designs in Phase I Dose Finding Clinical Trials
A phase I clinical trial is needed when a new drug or treatment is first used in human subjects. For ethnic reason, in such a trial, we have to carefully balance the possible benefit and harm so that the benefit is maximized and harm is minimized, which deems that the design is adaptive with small sample size, and is primarily focusing on safety end-points with efficacy end-points as secondary ones.Various adaptive designs have been developed to find a Maximum Tolerant Dose (MTD) with acceptable Dose Limiting Toxicity (DLT) rate pre-defined by investigators. Such designs can be grouped into rule-based designs and model-based designs. The widely used rule-based design is the 3+3 design1 whereas the most referenced model based design is Continuous Reassessment Method (CRM).2 In a 3+3 design, dose escalation or de-escalation depends on the toxicity of current dose through assigning group of 3 patients to a dose. It follows an up and down algorithm or a random walk rule according to which we choose dose adaptively based on toxicity.