Project Management Approach

Genelife Clinical Research is among one of the few CRO’s who have adopted Project Management Approach. This model widely helps us conserve timeline and cost. This model is predominantly devised from and for complex studies like cancer, cardiology clinical trials, but it can be retrofitted to other therapeutic areas. The basis of this model is the disease surveillance study which we conducted across India to study the trends of diseases.

Clinical Research industry demands quality data in most cost effective manner, we have designed Genelife Model. Industry trends and patterns have changed due to economic slowdown which suggests cost effective research and CRO can be best partner to achieve the same. 

In this model we have taken the Clinical Research process as a system and we identify exact input with well-defined process to bring effective output. The first input comes from Study Feasibility Analysis (SFA) Site Feasibility analysis (SFA); due to available disease prevalence data this process has become very fast and cost effective for us. This procedure is conducted on the basis of initial Project Plan (PP).

Study & Site Feasibility Analysis (SFA): Genelife Clinical Research has feasibility which works under Project Management Team. This team understands the objectives of the study and provides the solution to main question of project like what to be done; how to be done; at what cost; in what time. During site feasibility we emphasize on site not only with high disease prevalence but also with clinical research supportive environment. Clinical Research supportive environment is very important aspect for physician referral and it is not considered most of the time. 

Project Planning (PP): in our model we have divided Project planning in two major parts. In 1st is for initial phase is for training and performing initial activity like feasibility. After receiving the feasibility reports we develop plans like risk management plan, communication plan, QA plan, safety plan, monitoring plan, Data management Plan, SAP plan etc for stating how to complete a project within a certain timeframe, usually with defined stages, and with designated resources. In totality the plan will include setting quantitative objectives, identifying deliverables, identify & manage foreseen and unforeseen risk, overcome bottleneck planning the schedule and making supporting plans.

Project Management & Commencing: Once a project moves into the Execution Phase, the project team and the necessary resources to carry out the project should be in place and ready to perform project activities. The project team handover the activities to different departments and start analyzing the progress of work. 

Last stage of this model is suitable output which is directly dependent on above two steps. As per Genelife Model, with precise inputs and efficient process, one tends to get desired output in terms of faster regulatory approval, quality data, shorter timelines and better return on investment.

Representing

Genelife Clinical Research – Project Management Department

The Challenges with Drug/Device Combination Products

Active medical devices are that device which interact with the body systems and is has been highly effective. Drug is a common active component of medical devices such as inhalations sprays, nebulizers, stents, some orthopedic implants etc. . When the devices are merging, there is always a look to how two industries can merge at least for common interest areas to have compact medical package. Although the concept primarily looks to be invaded by issues, still situation is practically manageable. Several large companies in other business segments and a few hospitals manage several disciplines already.

For this, we need to collate some factoids for comprehensive evaluation of the situation. As the interrogator has correctly put the three areas to bear the primary stress will be regulatory, engineering and Quality. One functional sect area that would bear a lot of stress will be training. The segments those will be eased by this merger will be clinical, marketing and finance. The functionality of merger is integral in most segments other than production. There can be two scenarios about production facility: First, production of Drugs and devices in the same facility, and Second, Production of Drugs and Devices in two distinct facilities. The second case looks to be more feasible model for regulatory and engineering reasons. There can be two units in one premise, but intersecting utility is practically less possible for execution.

The first and the major impact will be on the regulatory and QMS professionals who need to manage compliances for highly diverse set of regulation in one infrastructure. The first scenario is when there is complete merger including production units. Let us discuss the compliance factoids of Audits in both cases. Good Manufacturing practice applies to both, Medical Devices as well as Drugs, with some fine tuning required. In This case, meeting systemic requirements of ISO 9001 and to an extent GMP will be relatively easy. Contrarily, it would critically elevate challenge in compliances for ISO 13485 and US FDA CRF section 510k. Some parts of medical devices will interfere with drugs production and vice versa. Storage, recycling and disposal needs; water, ground clearance, environmental needs, Infrastructure and machinery needs are three sets of diverse requirements. Compliances of these three sets are commonly seen to be antagonists to each other and hence is an edge-walk for Quality managers. The Regulators would face several constrains in Audits and inspections for intersecting facility. When the facility is intersecting, for all practical reasons they need to operate as two different units. Otherwise, they will keep complicating each other’s regulatory requirements.

Similar load will be taken by engineers, responsible for maintenance of infrastructure and machinery. Medical devices require sterilization of the products and drugs do not. Some byproducts of medical devices such as ETO fumes are known to have adverse effects on composition of pharmaceutical agents, and a few raw materials of pharmaceutical agents may have corrosive or other chemical impacts on raw material or finished goods of medical devices. The Engineering section has to develop efficiency in handling the diversity and counterproductive nature of some components in merging systems. Requirements of Maintenance in terms of Air Hosing units, Backups, machinery etc. will rage very wide.

With the merger of production and other facility of medical device and drugs, certain unforeseen manageable issues may pop up as the progress in fields is seen, yet it will be highly optimistic step up in reducing healthcare cost and deliver even better quality. Costs of regulatory set up, human resources, clinical, Engineering, benchmarking, preclinical and quality check testing etc. will significantly reduce. Marketing strategies like product bundling, in-house production of active components like drugs, polymers and merging of logistics, transportation, storage and corporate requisites will help availing quality products in minimum costs. When weighing Risks and challenges vs. benefits the the homeostatis shifts towards the merger.

Dr. Ashish Indani

Head, Clinical Operations

GENELIFE CLINICAL RESEARCH

29/243, Unnat Nagar II,

Off SV Road, Goregaon (W)

Mumbai 400063

Maharashtra, INDIA
Email: ashishi@genelifecr.com

Under The Scanner : Medical Device Trials

Our Managing Director, Dhirendra V. Singh has featured in the march, 2012 edition of Express Pharma, which is entitled "Under The Scanner : Medical Device Trials,", please find the link below:

http://www.expresspharmaonline.com/20120331/market01.shtml 

Though this article is written by someone else, but we believe that this article provides clear picture of Indian Regulation related to medical device. 

Genelife Clinical Research IInd Anniversary Celebration

Genelife Clinical Research has successfully completed second year with all the enthusiasm of work, challenges and fun that was put together and served in the field of clinical research. At this propitious occasion I would like to share the progress and furtherance of Genelife Clinical Research. As on 26th February bookmarked in our diaries permanently I would like to thank every helping hand that has made Genelife Clinical Research to be what she is now. 

The year started with the farewell of one of the partner of Genelife and we are planning to end this financial year as Private limited company.

After initial hiccup the year started with an Oncology Clinical Trials followed by a Asthma Clinical trials. Ad hoc, we have two new oncology studies, two medical device studies that are ameliorating and an all-encompassing presence globally. Also there are five studies which are waiting to be board. 

Genelife has also augmented its reach within therapeutic areas and developed a good rapport with the investigators and clients that we have come across in any projects at hand. Though even there are some minor mistakes that may have happened, but it is said that "a mistake is simply another way of doing things" so we improve and move on to correcting them and bettering the quality of work. Genelife Clinical Research has continued to identify and screen fresh sites and potential investigators in any kind of upcoming studies as we believe in keeping an open mind and a compassionate heart.

In order to upgrade the system to be “the most respected CRO” Genelife Clinical Research has introduced Data Management System with a well-qualified staff. We have also changed the location of Genelife from Thane to Mumbai (Goregaon). The working space of the new office is more which is essential for us to serve the needs of Clinical Research with the number of growing projects.

On international front also Genelife Clinical Research has shown her presence. We are waiting to take 3 TGA (Australian Regulatory Body) projects on board and planning to start a Russian medical devise project. Also in concert with the GCC government authorities our company has been exposed to the new elements of research industry. Apart from this Genelife Clinical Research has also identified the location at places like the United States and Germany in order to expand our operations in North America and Europe.

This all is possible because of our client, support and well-wisher and we would like to thank & show heartiest gratitude towards our clients and well-wishers for all the support and stand provided till date and surely time ahead.

"And no we don’t know where it will lead; we just know there's something much bigger than any of us"

"Each year has been so robust with problems and successes and learning experiences and human experiences that a year is a lifetime here... so this has been two lifetimes for us...”

Regards

GENELIFE CLINICAL RESEARCH

Email: info@genelifecr.com


Website: http://www.genelifecr.com/ Blog: www.genelifecr.blogspot.com

Clinical Research: Ethical concern and associated with Oncology Clini...

Clinical Research: Ethical concern and associated with Oncology Clini...: Cancer is arguably the most fatal disease. It is estimated that one third of drugs under discovery or development are for Oncology, but s...

GENELIFE CLINICAL RESEARCH: STEPPING TO NUTRACEUTICALS

After a prompt start in conducting a clinical trial for DCGI submission on a therapeutic area of Asthma, Genelife Clinical Research is all set to start a trial of Nutraceuticals on Breast Cancer. The term

"Nutraceuticals" may require a brief introduction. Nutraceutical is a word introduced by US FDA for possibly a pormanteu of "Nutritional" and "pharmaceuticals". Health Canada defines the term as, "A Nutraceutical is a product isolated or purified from of foods or food like material that is generally sold in medicinal forms not usually associated with food. A Nutraceutical is demonstrated to have a physiological benefit or provide protection against chronic disease. These may range from isolated nutrients, dietary supplements and specific diets to genetically engineered foods, herbal products, and processed foods such as cereals, soups, and beverages." In a nutshell, Nutraceuticals are Natural Adjuvant having affirmative medical and health benefits; including the prophylaxis of disease, maintenance of nutrition and basic health profile and restitution of cumulative aftereffects of treatments received. Major Indications also include facilitation of desirable therapeutic outcomes of concomitant therapeutic agents. All these indications are for improving quality of life in subjects who are healthy or dependent upon long-term medication and has met with great monetary success.

Genelife is reaching out with nutraceutics to the world’s third most common cause of mortality, the Cancer. In this condition Morbid and uncontrolled division of cells and their invasion into other tissues lead to formation of malignant tumors and cause impediment to the life process”. Breast cancer being one of the most common types of cancer, is taken a basis for this study. Planned typical treatment of Breast Cancer, just like most others, includes surgery, radiation therapy, chemotherapy either singular or in combination. With the evolvement of radiation therapy or chemotherapy, the Life expectancy, five years survival rate, retardation of disease process is achieved. Unfortunately, the therapy; due to its side effects; has significant deterioration in the quality of life. To overcome this, Ocimum has developed a herbal Nutraceutical product and successfully tested it in animals. This formulation is a plant extract expected to reduce cumulative after-effects and side-effects of treatments of cancer and also helps in improvising in the quality of life. REFORM 1 ca is a randomized single-center, placebo controlled, study for safety and efficacy outcomes of one of this herbal adjuvant in a close small cohort. As a Strategy of study, the subjects will continue with prescribed treatment such as chemotherapy or radiotherapy. This study is powered and designed to achieve the outcome listed down:

• Improving the quality of life

• Reducing the side effects of chemotherapy / radiation therapy given as a treatment of Breast Cancer

Innovative study design as a "Genelife factor" has made the study interesting and adorable. The outcomes of the study are looked forward to introduce new heights to all Nutraceutical industry and hopefully sooth sufferings of Cancer patients.

Thanks & Regards,

 GENELIFE CLINICAL RESEARCH

CLINICAL RESEARCH IN MEDICAL DEVICES –Innovative Designs to overcome constrains

The Clinical Trials of medical device's are complex in comparison to drug. So, one has to design the study to overcome the constrains in medical device clinical trials, especially pertaining to comparability and establishment of universal outcomes. There is no perfect control in a medical devices study. Moreover, as there is no “Absolute safety and efficacy” available from experimentation in healthy human subjects, the outcomes of studies remain majorly study specific. Applicability of the trial outcomes to real world is grossly limited.

One of the major problems in Medical Device clinical trials as discussed is lack of a perfect control. Even if some control is selected, the control may have different indications. For example, Stent implant angioplasty and coronary artery bypass graft are the common comparable entities. Both of these treatments and thereby the device “Stent” is studied against a control of CABG. If seen in further details, the coronary artery bypass graft is indicated for some different subset of coronary artery stenosis than angioplasty by stent. Hence even after several trials including ambitious large trials such as Freedom and Subgroup trials such as MAIN-COMPARE, the dispute of which one would be a better treatment was still on. Not this alone, but several other conditions where medical device needs to be compared with a control, which is usually not a perfect control, the outcome is usually disputed. Higher the data available, higher is the confusion. What could be a suggested solution?

Among these, SYNTAX was a trial, which was able to establish some results and lay down definitive guidelines to an extent though. What differs in SYNTAX from other studies was design of the trial. The trial was designed based upon minute details of the therapeutic variations. For comparability, they established a score and made it a compound trial.  In only a few other cases, such as LEADERS trial, due to an innovative study design, the outcomes of the trials are closely matching to the real-world observations, unlike many other studies such as from SPIRIT group, Endeavor group, where the outcomes fail to match the day to day clinical outcomes.  This makes the point that innovative study designs can overcome some major constrains in Medical Device Clinical trials and can yield reliable and more accurate clinical data which can be used as a standard reference in day to day clinical practice.

What can be different designs of studies? There can be several design options. The first is variation of the hypothesis. In many Medical Device Clinical Trials, the study hypothesis is developed in a way that specific outcomes are tested. For example, in many studies, the hypothesis is designed to register an “Event Free Survival” or “proportion of population free from events in a defined period”. Though these both study questions sound good, practically, the comparison of a medical device on these outcomes is too vague to prove anything in favor of any of the arms. Instead, if the same evaluation is defined in a converse, such as “frequency of adverse events reported in a particular period” or “time taken to relive or produce desired or undesired effect” would be more specific and in a smaller group of population, a better study outcomes can be obtained.

The second important postulate of an innovative study design is inclusion of subsets. In many conditions it is seen that the study design exclude many subsets of the populations, which make the results differ from “real world” scenario. Instead, the predetermined subsets inclusion can give a study a wider acceptance and better power. In fact, based upon this one postulate, the study can be an union matrix study, a multi-arm study, overlapping matrix study etc. These designs are uncommon to use but an intelligent statistician will take efforts to make these ambitious designs. These types of designs may have several expressions such as compartmental design (Tight Subset matrix), blocks design (Loose Subsets Matrix) , clusters design(Loose subsets with stratified or multiple overlapping) ; and the study cohort can be stratified to establish relative betterment.

When a device has no perfect control, but if it is considered to be remedial in a particular condition, way of designing the study is multiple controls. This design of study enables the researcher to establish practical comparison of the device with several aspects of treatment such as untreated subjects, Subjects treated with one or more other modes, Subjects treated with device alone, subjects treated with device and subjects treated with combination of therapies. This type of study can be best suited to derive outcomes for new types of devices. The other type of designs can be compound design of multi-arm and single arm trials. This design is best suitable when there is an established treatment for some particular condition. The device which is either new or newly indicated for this condition is to be compared with established treatment. In This scenario, there can be great variance of indication of the device and the established treatment within the same condition. This complexity can be addressed by a compound design of the study, making the arms comparable more correctly. 

 Use of Standard or Specifically developed scores can be one of the important tools in design for Medical Device Clinical Trials. The Standard Scores Such as Comorbidity Index, Medina Score for Cardiology bifurcation lesion or Study specific scores such as SYNTAX Scores can be highly useful in designing a study and meet specific comparability needs.

Dr. Ashish Indani
Clinical Operations Head

GENELIFE CLINICAL RESEARCH

33,34,37 Ground Floor, Cinewonder Mall, Ghodbandar Road, Thane West-400607. INDIA
Telephone:             +91-(0)22-65242666                   +91-(0)983316130       Fax: +91 22 25841316
Email:  info@genelifecr.com Website: http://www.genelifecr.com/, Blog:http://genelifecr.blogspot.com/

Clinical Research: Oncology Clinical Trial: Long Timeline and Breakth...

Clinical Research: Oncology Clinical Trial: Long Timeline and Breakth...: Millions of dollars are spent on creating new treatment methods for cancer. The main reason for high cost of cancer treatment method is lo...

CLINICAL RESEARCH IN MEDICAL DEVICES

Medical Devices are any therapeutic or diagnostic agents or their accessories, which work on non-biochemical mode in the body.  The primary scientific consideration in medical devices clinical trials is determination of ‘Which devices require clinical trial?” or “Does my device need clinical trial?” to undergo clinical studies.

WHICH MEDICAL DEVICES REQUIRE CLINICAL EVALUATION?

In Medical device life-cycle, preclinical bench-top analysis for mechanical and design tests; are the major determination criteria for acceptance of that device. It can be considered as Phase 0 studies for medical devices. Unlike the drugs, feasibility of medical devices practically is done in a combination of engineering tests and Animal studies. The pre Clinical studies become more important in medical device compared to drug because the evaluation of Medical devices (Both performance and safely) depends upon its adverse event occurrence (In contrast to drugs where Pharmaco-dynamics and tolerance are major safety endpoints and bioavailability and Improved life quality are performance outcomes).

From clinical research perspective, medical devices can be classified into four main categories-Therapeutic (Whether active or inactive), Non-therapeutic-non-diagnostic (Accessory), Diagnostic and Contraceptive medical devices.

The clinical trials for diagnostic devices are wider and diagnostic test outcome oriented. The clinical trials are required only to introduce new techniques. Same is the case with contraceptive devices. Contraceptive devices studies are mainly failure oriented single arm trials and accessories do not require clinical trial for regulatory or clinical evaluation.

The therapeutic medical devices, which mainly require clinical evaluation, have mainly two types, Implantable and external. The implantable devices includes Pacemaker, stents, arterio-venous fistulae, dental implants, orthopedic implants etc. and the non-implantable group include Cardio-Pulmonary Resuscitation (CPR) Devices , Heart and Lung Machine, Dialysis unit, Defibrillator (External) etc.  Clinical trials in these Medical Devices are major concentrated on its performance and safety analysis. Most devices in this group need repeated confirmation of utility by clinical trials.  Highly dynamic devices like stents hence require recurrent validation. Similar but relatively less severe is the case with a pace makers etc.

PHASES IN MEDICAL DEVICE CLINICAL TRIALS

Unlike drug Clinical studies medical device clinical trials can be divided into three phases:

1. Pilot Clinical Trial

2. Pivotal Clinical Trials

3.   Post Marketing servilence

Study types	Primary Intention	Desired outcomes	Points to be evaluated
First in human Studies	1.       Feasibility of the device in Human subjects	1.Non-inferior performance over control arm	1.       Logical Reasoning for determination of given endpoints (Cross check animal data)
	2.       "No Additional Risk" profile of the device	2.       No Additional risk over control arm
	3.       Performance of the device in target condition
	4.       The studies are  performed in Simple population for performance demonstration; have lowest risk		2.       Other parameters if missed by study reporting (Source Animal data)
Pivotal Studies	1.       Safety and efficacy of the device in human subjects	"Safe for human wider human use"	1.       Performance of the device in given end points (efficacy / safety)
	2.       Performance of the device in target condition		2.       Methodology of study
Post marketing surveillance	Evaluation of Device in more defined / Difficult subgroups	1.       Performance and safety in More difficult conditions	1.       Effect of parallel medication etc
		2.       Marketing tool	2.       Study methodology
			3.       Preserved safety interest

CONSTRAINTS IN MEDICAL DEVICE CLINICAL TRIALS

Like drug, it is necessary to evaluate the safety and efficacy of medical device before for marketing approval.  Apart from that medical devices will require performance evaluation, which makes the medical device studies more tricky compared to drug studies.

Another biggest constrain in most of the medical devices is lack of a perfect control. In most cases, earlier treatment by surgery, drug or previous generation device may also not prove a good control as indications in higher versions may differ from of the previous. Classical examples are randomization of stents against Bypass surgery, renal transplant against repetitive dialysis, Drug eluting liposuction versus pseudo-trimmer devices are all non-decisive. In most of these cases, even the design of the study was a challenging job. Even in previous versions of devices, there is similar propensity. DES versus metal stent, ERCP device versus laparoscopic cholecystectomy apparatus failed to achieve even primary endpoints due to lack of specificity in comparisons.  Wise design of the study is important to mitigate such failure risks.

Apart from this, human safety is still a major clinical and ethical concern especially with implantable device related clinical procedures, as most of them are almost irreversible. Taking for example, a coronary stent, once implanted, even if it causes complications such as stent thrombosis, has no way to reverse the implant. Clinical studies for most of the therapeutic medical devices, unlike drugs, again are not possible in healthy subjects. Hence, there cannot be an “absolute safety” outcome for any medical device.

Another constraint is scope of error, which is very less in case of medical device clinical trial.  Clinical data from all phases of medical devices is used as a very critical selection criterion by medical practitioners. Yet, making out-standing scientific value for the study and its outcome is difficult due to “lack of innovation” in many cases. Except a few clinical trials like REALTY, SYNTAX, LEADERS for DES, and a few more for Nephrological, neurological and urological devices, there are too few innovative designs. Achieving “Superiority” is also difficult task in medical device trial. Pertaining to all these major points, there is a lot of opportunity for young scientists to invest their mind in making several developments.

Indian Clinical research industry is progressively developing and adding newer segments to its overall expansion. In last few years, Medical Devices have made a significant share in the overall statistics. Considering the regulatory scenario, most of these trials take place simply on a notification. A few CROs like Genelife in Mumbai, have taken initiatives in making medical device based clinical trials more innovative and standard. Even if in current time there are no many pilot/pivotal studies and FIM studies taking place, we see closest future having wider prospects and scopes for Medical devices clinical research in India.

Kind Regards,

Dhirendra V. Singh
Managing Director

GENELIFE CLINICAL RESEARCH

33,34,37 Ground Floor, Cinewonder Mall, Ghodbandar Road, Thane West-400607. INDIA
Telephone: +91-(0)22-65242666 begin_of_the_skype_highlighting            +91-(0)22-65242666      end_of_the_skype_highlighting Mob: +91-(0)9819055580 begin_of_the_skype_highlighting            +91-(0)9819055580      end_of_the_skype_highlighting Fax: +91 22 25841316
Email:  info@genelifecr.com Website: http://www.genelifecr.com/, Blog:http://genelifecr.blogspot.com/

Genelife Clinical Research: Onging Respiratory Clinical Trials on Asthma

Genelife Clinical Research has started its first study for DCGI submission. After playing significant role in conducting pre-clinical studies and global US FDA studies, Genelife Clinical Research has given a progressive start for its first trial for DCGI submission for “Asthma”. As known, Asthma is a common chronic disorder of the airways that involves a complex interaction of airflow obstruction, bronchial hyper responsiveness and an underlying inflammation. This interaction can be highly variable among patients and with patients over time. The study is a prospective “A Multi-Centric, Double Blind, Randomized, Comparative Clinical Trail to Evaluate the Efficacy and Safety of ZU/SER10 in the treatment of Asthma”. In this study the test Drug will evaluated against "Montelukast" one of the best Drug of Asthma. In this study we have to generate data for 200 completed subjects across four sites in two months of recruitment period. 

The identification of site was based upon historic performance metrics, type of Institute and its geographic location, paramedical staff, Investigator’s qualifications and their availability for the entire duration of the study, and most importantly their recruitment rate. And to get all the details we performed a feasibility assessment by telephone to determine each PI’s availability, interest, and ability to meet study requirements and procedures.These identified sites comprise of both private institutions as well as government institutions to recruit patients from all economical sets. 

Considering the patient recruitment as bottleneck, we at Genelife stressed a lot on selection of right site. Recruitment rate has become more important criterion considering the short recruitment duration. We performed the site selection process with outmost care. 

During the site selection processes we have carefully observed the facilities available at site, their patient recruitment rate and their training & amp; knowledge about ICH - GCP guidelines, performance of site in previous trials for a similar indication, audit findings, patient recruitment, lost- to-follow-up rates and finally, results of site selection visits. Site staffing, ability to communicate internally and externally, experience in the area of clinical trials, and logistical handling of case report forms and other data collection instruments. For this particular study we have selected four sites and those are at Mumbai, Lucknow, Hyderabad and Varanasi.

For this Asthma study we have generated additional Logs, to reduce the percentage of errors and discrepancies considering the number of data to be generated at site by the investigator. 

Genelife Clinical Research has improved its facilities for conducting this Study in order to provide high Quality Standard.

Thanks & Regards,

GENELIFE CLINICAL RESEARCH

E mail :  info@genelifecr.com

Blog    : www.genelife.blogspot.com