India is increasingly becoming an attractive destination for clinical research for pharma groups looking for faster and more efficient ways to test drugs for western countries

India is increasingly becoming an attractive destination for clinical research for pharma groups looking for faster and more efficient ways to test drugs for western countries, United Nations Conference on Trade and Development said on Thursday.

It has been estimated that firms can reduce costs by 20-30 per cent by moving their R&D activities to India, UNCTAD's World Investment Report 2005, said.

However, the new patent regime in the country has eroded the power of domestic pharma companies to absorb knowledge spillover through reverse engineering, Nagesh Kumar director-general of Research and Information System for Developing Countries said while releasing the report.

So while the patent regime has reduced the power of domestic companies for absorption of knowledge dissemination on the other hand it has made India an attractive country for clinical trials, said Kumar.

The UNCTAD report said savings for firms going for clinical trials in India come from hiring researchers, nurses and IT staff at less than a third of wages in the West, in addition to differences in the costs associated with the patients.

However, there are some factors holding back the development of clinical research in India such as relatively slow approval process, the report said.

"Another one is India's reverence for animals, which makes it difficult to use certain animals (like monkeys)," the report added.

India, which is well-endowed with skilled R&D personnel, also has a substantial number of people with diseases that exist in developed countries, making it a favoured destination for clinical trials, according to the report.

India has up to 30 million people with heart disease, 25 million people with type-II diabetes and 10 million with psychiatric disorders, the report said.

The country also has a large pool of "treatment naive" patients who have not yet been exposed to other drugs in the market, UNCTAD said.

"In addition, Indian recruits are more likely to comply fully with the trial process, unlike in developed countries where a significant proportion of subjects drop out in order to seek second opinions," the report said.

It is estimated that the number of clinical research organisations based in India increased fourfold between 2001 and 2003, UNCTAD said adding Indian firms, too, are participating in this new industrial activity.

One factor apparently underpinning the shift has been India's newly adopted guidelines on good clinical practices, including the issue of consent by the patients in line with global norms, the report said.

However, other commentators have questioned what consent can mean in a drug trial when patients are illiterate and might not adequately understand the experiment's true risks.

"By definition, the drugs being tested have unknown beneficial effects on the patient's illness or disease, and negative side effects are also unknown," the report pointed out.

Clinical trials in India:rising outsourcing of clinical trials to India, with concerns about little benefit or relevance to the public health needs of the country

Clinical trials in India continue to be in the news, unfortunately a fair bit being negative coverage. Over the last few years, there has been continuing outrage on the issue of rising outsourcing of clinical trials to India, with concerns about little benefit or relevance to the public health needs of the country. While this dust has not even settled, allegations of unethical conduct in clinical trials have again brought a focus on the need for regulatory reform and stringent ethical safeguards.

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THE CONTROVERSY ON TRIALS IN INDORE

The recent reporting of controversial drug trials being conducted by doctors of the government medical college and private practitioners on ‘mentally challenged’ patients in Indore has caused uproar. It was alleged that for more than two years, from 2008 to 2010, trials were conducted flouting ethics guidelines. The Madhya Pradesh government levied a fine of Rs 5000 each on the doctors involved, and this was seen widely as being paltry and insufficient punishment. As details emerged, questions were raised about the role of independent or commercial (as compared to institutional) ethics committees, improper documentation of consent, vulnerability of research participants as well as the thorny issue of private practice (and in this case, research in private clinics) by government doctors.

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GROWTH OF THE CLINICAL TRIAL INDUSTRY IN INDIA AND ETHICS VIOLATIONS: IS REGULATORY REFORM ENOUGH

Research being conducted by pharmaceutical and biotechnology companies in India has been on the increase. Added to this, has been the mounting quantum of outsourced research facilitated by Contract Research Organizations (CROs) with the promise of cheaper and faster conduct of trials as compared to the west. From 40 to 50 trials in 2003, the country saw around 1850 trials registered with the government registry in June 2011. Mushrooming clinical research courses, often unregulated, have sprung up with an aim of servicing the need of personnel for conducting clinical research.

While the escalating research quantum has, to some extent, served to benefit the Indian population which now is undergoing a demographic transition with both infectious and non-communicable diseases being commonplace, it has also raised concerns that ethical conduct is often forgone when the primary interest increasingly is profit generation. The specter of unethical trials being frequently reported is a reflection of an ailing and substantially ineffective research regulation system in India. While biomedical research in the country has increased exponentially in the last decade, reforms in regulations have only occurred at snail's pace. Intent has been demonstrated towards such reform, but needs to be substantiated with priority policy changes. Regulatory progress is only one element of the solution—other steps are also needed to move forward in this area.

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WHAT NEEDS TO BE DONE?

It's quite clear that there is a need for reform. Improvement has already been seen in certain areas, such as the stress on clinical trial registration in India through the medium of the Clinical Trial Registry -India (as well as Indian journals insisting on such registration for accepting resultant manuscripts). The increasing awareness about ethical requirements in research, as well as the role of activists in questioning trial conduct when deemed exploitative, has also resulted in a positive change to some extent. However, a lot still needs to be done. This requires a multi-faceted approach and involvement of all the stakeholders with an aim for more robust science, which incorporates a strong commitment to ethics.

Stringent regulations and laws

The role of stronger legal oversight, in light of the guidelines not serving to be enough in curbing deviant research conduct, cannot be emphasized enough. Advocacy is needed, so that the draft bill on Biomedical Research on Human Participants (Promotion and Regulation) prepared by the Indian Council of Medical Research is put in the public domain for discussion and refinement, and is then tabled in the parliament on a priority basis. Such a law can provide mechanisms for legal remedy in the case of questionable and/or exploitative research.

The number of Ethics Committees (ECs) in the country is rising, but there is no clear estimation of the total numbers. The quality of conduct of ECs is often quite variable, and also there is no standardized training or orientation for members. Unless there is mandatory registration of ethics committees and an accreditationprocess, it would be difficult to ensure that ECs are optimally focusing on their core duty of protection of research participants. In a positive development, some ECs in India have voluntarily undergone accreditation through the Forum for Ethical Review Committees in the Asian and Western Pacific Region (FERCAP), and the Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRP). Indian EC members who were surveyed in the past, also felt that there is a need for formal training of EC members in ethics, and networking of ECs. The Forum for Ethics Review Committees in India (FERCI), which recently conducted its first national conference, could serve as a platform to respond to these needs. E-groups and online discussion forums have also helped in providing avenues for sharing of experiences and updates. ECs also need to proactively engage researchers and conduct on-site monitoring of projects; this can help in identifying and addressing transgressions.

The role of mentorship is crucial in training research investigators. If the mentors demonstrate and require that trainees conduct research of a high standard, it can help a great deal in producing researchers for the future, who do not cut corners and believe strongly in scientific integrity.

Transparency is one of the core guiding principles in the ICMR Ethics Guidelines. Institutions and investigators need to put more information into the public domain: About the kind of research they are carrying out, the rationale for choosing a certain set of participants and the interventions, the standard of care in the research, ancillary care and post-trial obligations etc. While it might not be possible to always disclose proprietary information related to the intervention or some elements about the research, the relevant ethics committee should at least insist on full information being provided. Another area where enough attention is not often paid is the EC demanding to see the budget of the study, the details of any MoUs signed with the sponsors, as well as details of other sites (in a multi-site study).

Global attention is now being paid to the need for public engagement in science. There is a need to enhance the public understanding for research, and to develop a civic dialogue around what kind of research is necessary. This will help in creating widespread support for scientific endeavors. Mechanisms of communication being present between research participants and the communities they belong to, and between the researchers and ECs will help avoid misunderstandings developing due to a trust deficit. Scientists should also use the media at local and national levels to explain the rationale for the research which is being conducted, and how it relates to the health priorities in that context.

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CONCLUSION

India, as an emerging economy needs to continue to promote a strong culture of research and development, including in the health sector. However, attention needs to be paid to ensuring that stringent quality checks are built in, and that investigators conduct research in an impeccable manner. Failure to do so will dent the credibility of the research enterprise, affecting not just investigators or institutions conducting research, but also those planning to do so.

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Footnotes

Source of Support: Nil

Conflict of Interest: None declared.

Doctors Surgical Strikes

What is the difference between Clinical Research Organization & Contract Research Organization

Due to the increasing costs of managing the research internally and focus on core competencies, many of the pharmaceutical companies have come up with the idea of outsourcing their Discovery Development, Per-clinical Trails and Post-Clinical trials and Legal Processes to players who specialize in these areas. Please note that the forte of the pharmaceutical companies vary and hence the outsourced activities also could change accordingly. Like Novartis is known to have taken a decision not to outsource the discovery services where they opine that they have the core competence.

A Contract Research Organization is a company that is capable of taking up all or some of the activities in the pharma-biotech value chain. Example: Wuxi Apptech

However some of these companies have specialized in specific areas like:

Discovery and Development Services: GVK BIO

There are some companies that specialize in Clinical Trails. They work on both animals and human beings (volunteers) to finalize the pre-clinical and post-clinical trails. Example: Quintiles

PS: However owing to continuous changes in the geo-politics and the requirements of the companies, the differences are blurring between these companies.

While contract research organizations can span the entire pharma pipeline from drug discovery to clinical trials and beyond, a clinical research company mostly manages clinical trials. People in the R&D business often consider clinical research management companies a subset of the broader CRO category. But those in the medical and public health sector tend to consider clinical research organizations their own species, unrelated to CROs that focus on bench work.

A contract research organization (CRO) is an organization that provides support to the pharmaceutical, biotechnology, and medical device industries in the form of research services outsourced on a contract basis. A CRO may provide such services as biopharmaceutical development, biologic assay development, commercialization, preclinical research, clinical research, clinical trials management, and pharmacovigilance. CROs also support foundations, research institutions, and universities, in addition to governmental organizations (such as the NIH, EMA, etc.).

Many CROs specifically provide clinical-study and clinical-trial support for drugs and/or medical devices. CROs range from large, international full-service organizations to small, niche specialty groups.

CROs that specialize in clinical-trials services can offer their clients the expertise of moving a new drug or device from its conception to FDA/EMA marketing approval, without the drug sponsor having to maintain a staff for these services.

Regulatory aspects

Specifically pertaining to CROs providing clinical-trials services, the International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (E6 1.20) defines a Contract Research Organization (CRO) as: "A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor's trial-related duties and functions."

• (5.2.1) A sponsor may transfer any or all of the sponsor's trial-related duties and functions to a CRO, but the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor. The CRO should implement quality assurance and quality control.
• (5.2.2) Any trial-related duty and function that is transferred to and assumed by a CRO should be specified in writing.
• (5.2.3) Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor.
• (5.2.4) All references to a sponsor in this guideline also apply to a CRO to the extent that a CRO has assumed the trial-related duties and functions of a sponsor.

Market size and growth

There are over 1,100 CROs in the world, despite continued trends toward consolidation (many CROs are being acquired in recent times or others go out of business). It is a very fragmented industry with the top 10 controlling 56.1% of the market in 2008 and down to 55% in 2009. One estimate had the size of the market set to reach $24 billion in 2010 and set to grow at a rate of 8.5% through 2015.

However, more recent data reveal a 15.5% increase in R&D spend from 2015 to 2020.

As of 2016, the top 10 CROs by revenues are considered to be:

1. Quintiles ($4.3B revenues in 2015)
2. Covance ($2.5B revenues in 2014 before its acquisition by LabCorp)
3. Parexel ($2.1B revenues in 2015/16)
4. inVentiv Health ($2.0B revenues in 2015)
5. Icon plc ($1.57B revenues in 2015, headquartered in Dublin, Ireland)
6. PRA Health Sciences ($1.4B revenues in 2015)
7. Pharmaceutical Product Development ($1.35B revenues in 2014),
8. Charles River Laboratories ($1.4B revenues in 2015)
9. Chiltern International Ltd. (approaching $1B revenues)
10. INC Research (approaching $1B revenues)

Can a teenager start a clinical Research Organization?

I’d love to say YES! to this, and I fully support you. But unfortunately, the chances of it being successful are slim. A business, yes. Teenagers start them all the time. In fact, with one of the subjects at school (I don’t take), the aim is to start your own business and be as successful as possible, and pit yourself against other companies set up by other school students.

However, a Clinical Research Organisation, as good an idea as it is, is probably out of the realms. 99.99999% of them (not a precise number, but it shows the chances) are run by people with university degrees in science, and you won’t have them at high school (I think).

What you both could/should do is take a free period (i.e. drop a useless class or something), sit in the library and research it together. Talk to a professor (if you have one teaching at your school) and get them to help. Ask, and they’ll be more than willing to help, and they might even teach you how to write full-blown reports and do “proper” research. Not minimizing you and your abilities, but they might take you through the whole process. Once you get through uni (doing an appropriate course, of course), then you’ll have that edge above everyone else who wants to set one up.

Wanting to start a business is awesome. It’s a fantastic idea, especially for a teenager.

When starting a business, it’s important to have a passion for what you’ll be doing. Without this passion, you will likely give up too early. Given the fact that you and your partner share a strong interest in business and biotech, you’ve got the first requirement checked off your list: passion.

You also need access to the right resources. For instance, if you’re going to be working in a laboratory, you need the things that go in a laboratory. (As a software engineering guy, I don’t know what you’ll actually need in the laboratory … but I’m confident you do.)

One of the resources that a CRO needs is a site network. Pharmaceutical company P will come to CRO C and say (essentially):

P: “Can you conduct fast and accurate clinical trials on our new prostate cancer drug D?”

C: “Yes”

P: “Prove it.”

C: “We have a site network composed of 320 oncology clinics that specialize in prostate cancer. On average, they’re each capable of screening 10 potential trial participants per month.”

P: “Awesome. You’re hired.”

Okay, clearly that’s a super-abbreviated conversation. But you get the idea. The CRO, among other things, specializes in being the middleman between the sites and the pharmaceutical companies.

In order for your CRO to succeed, you’re going to need to figure out how to have access to a site network. Is it doable? Absolutely. Plenty of companies have figured out how to do it.

It’s up to you to decide whether you’re capable of figuring out how to do it.

How do I start a clinical research organization (CRO)?

Answer

Request

Science is a brilliant subject to study and explore. It can lead to myriad of careers, but what is a perfect fit is the biggest question. Often students get overwhelmed by the vast area to make the right choice. Well you must know everything about a career field before following the path. Once you earn the necessary knowledge; it would become easy for you to follow the route. Clinical research is one such booming field.

If you want to enter clinical research area; a healthcare science that confirms how safe and effective drugs, equipments and diagnostic products are, it’s the perfect sector for bright and talented science candidates to get involved in. If you’ve got a degree in science, medicine, nursing or pharmacy, you could be an ideal candidate for the position of Clinical Research Associate.

This role is an excellent stepping stone in the clinical research sector, giving professionals an experience of a corporate environment and a strong connection with science. It’s a rewarding career with lots of demand – but what to follow?

CRAs can later become Clinical Trial Managers or Clinical Operations Managers, but there’s also the opportunity to take lateral steps into slightly different fields. Be inspired from some of the ICON’s own team members.

It's not that easy stuff to open a CRO as Clinical Research (CR) is totally different industry as compared to others. You can do first Market research on CRO's.

How clinical trials run?

How many years to complete drug trail?

Then you can talk with industry people who actually have set up their CROs. How did they start problems they stucked, challenges they faced & most important you should have lot of experience of handling entire trials or have good team who has lot of experience in handling clinical trials.

Firstly, to define your work scope - project management, monitoring, data management, RA, medical writing, etc.

Then, to hire your talents

Last but very very important, have clients

You'll find questions you would like to ask yourself as you go along through this process of planning to begin a CRO in sweden, and you would like to inquire over and over again because your answers are going to constantly change.

Have you ever tested your notions?

Which means your business plan looks great. Have you gone out and brought it to individuals who learn more than you do and asked Am I barking the wrong tree here?

Are you aware the competitors really, very well, and just how they price?

Otherwise, you are able to know whether your value proposition is priced properly. You can't are aware that your pricing strategy will almost certainly fly using the customer.

Are you able to negotiate deals?

They need to be win-win deals, or perhaps you don’t negotiate successfully.

How's your network?

It better be pretty deep. Many scientists I’ve spoken to in pharma haven’t spent lots of time with network building beyond their narrow scientific field. You must know people outside your field and outdoors your industry.

Does asking stupid questions bother you?

It better not. I had to overcome that a bit myself in the early days and I learned that I truly liked it. I liked asking something which I was thinking was dumb, then letting them know that I thought I was being stupid, then permitting them to inform me what you know. It was actually an enjoyable experience. I much useful stuff here that way.

Should it bother you when other people inquire stupid questions, in particular, customers?

Any particular one is tougher to overpower sometimes.

Can you hate being wrong?

I understand people like this. They get into arguments and defend their position around the smallest thing. You can't be in this way if you're testing the minds of your strategic business plan.

Does one such as the job of CEO?

Does one actually know what that job involves? It doesn't involve doing the science that you think you will get into this to do.

Did you know accounting?

I didn't offer an accounting class while attending college. In the event, you don't know accounting then start reading books because this is completely vital.

Are you prepared to take no salary and have no insurance?

Just about everyone I am aware that has started a CRO and other biopharma business adjusted via a period where they've got had no salary. One of the best ways this can be done, and I hate to really make it appear to be its this dependency kind of thing, is to get a spouse with a great job with really great insurance. It's just like this the vast majority of the time. Those who take this risk in most cases have some personal backup.

Which is the best Contract Research Organization (CRO) in India?

India is traditionally known for pharmaceutical companies like Dr Reddys and Ranbaxy. CROs have started off in the country around 2000s and owing to the strict compliance and operational issues around the industry (like the distance from cities, disposal management, need for highly skilled labor) not many people have attempted and continued in this business. However, two names have emerged as the leaders from 2007 onwards.

1. Syngene
2. GVK BIO

Apart from these two companies, Advenus a Tata company is also growing fast.

If you ask which company I would love to work with as a client or as a employee, I will vote for GVK Biosciences. Why? Because:

Syngene is owned by a biotech company called Biocon that does its own scientific research. It innovates its own drugs and produces medicines. Why world I want to outsource my company’s info to a company that is also a competitor company of mine? So, I strike-off the possibility of working with Syngene.

GVK BIO is based out of Hyderabad, the pharma hub of India. The company has issues but those should not stop me from doing business. Advenus is also a good option as it is backed by 100+ year old Tata Group. But, still among these two companies, I will choose GVK BIO owing their experience in the domain of Contract Research Organization segment.

How can someone start a new Research and Development organization?

I want to start a for profit research and development company one day that will develop new technology for business and consumer use. How could I find resources and talent to make that happen?

The normal approach is that a company/organization that makes products and has profits (say, Google or IBM), at some point decides to fund a long-term R&D group. Since you don't have the money, in essence you need to raise it.  This requires you to write a Business Plan and then approach investors to fund you.   In other words, you need to show investors how your organization plans to make money and how you are indeed qualified to lead such an organization.

How much does it cost to hire a CRO (contact research organization) for clinical trial recruitment?

Among the very few training institutes in Pune that offer clinical research courses, CRB Tech Solutions Pune offers real time and focused clinical research training program. Our program is designed to transform Life Sciences graduates into efficient professionals who will add value to the companies who hire them. Our training course includes theories , internship, and development of soft skills that will increase your chances of employment, way ahead of your contemporaries.

You might find a few institute of clinical research that provide clinical research training in Pune but the need to take the right decision and follow the right institute in making a bright career.

Eligibility Requirements

Any one of the following minimum qualifications is eligible:

MBBS, BDS, BAMS, BHMS, B.PHARM, B.Sc. (Life sciences, Biotech, Nursing), Post Graduate Diploma

Mode of training

Class room training

• 4 Months Job oriented Internship Program
• Training and Internship in CR & CDM
• Access to live projects in Pune

ENROLLMENT

Offered twice a year.

Payment options:

With credit card & debit card, payment options for fees is flexible.

What sets up apart?

• 100 % placement guarantee on paper

• We offer LOI (conditional offer letter) from our clients

• Unlimited placement calls for both alumni and freshers

• Known for best walk-in drives.

• Placement with lifetime support.

• Mentoring by very talented corporate expertise faculties.

• Train in German language and hence enhance your abroad prospects.

• Personality development training which will benefit you in developing soft skills hat would help you in cracking interviews which are very important in standing up among other contemporary candidates in competitions.

• 95% practically oriented training sessions.

It depends on how hard it is to get the type of subject you're looking for. According to some estimates, recruiting can cost up to 30% of a trial budget. So, for a modest $25 million trial this can be millions of dollars in CRO fees.

There are tools that make make this easier for the sponsor to do this themselves, such as EHR / EMR data mining. John Halamka has a good blog on this, Life as a Healthcare CIO,
and we do too: Florence Healthcare Blog

How much does a clinical trial management system cost?

The question is how pharma R&D and clinical organizations control source data for local languages. This is currently one of the biggest issues facing clinical trial labelling and packaging.

At present, companies are struggling to find a reliable way to approve and lock down local language data – leading to the ever-present risk of products being incorrectly labelled, causing financial implications and risk to patient health.

Clinical trials are a global activity. As such, materials for clinical trial are now being shipped across many countries and many continents. Labelling, booklets and where necessary Instructions for Use (IFUs) must therefore be safely and accurately customized not only so that they are in the appropriate local languages, but also to ensure that the problems of those local languages are understood appropriately to communicate well with clinicians and patients. They must also abide by country specific needs; in certain countries additional information, such as the name of the trial organization or specific medication removal notices, has to be stated by law.

There is currently a huge degree of inconsistency in how organizations across the sector are approaching this important issue – some of which are prone to human error. Where companies have developed in-house processes, there are often a number of disparate systems involved in managing language, label/booklet design, approvals and final printing. Conversely, some organizations still rely on onerous manual processes – at great cost in terms of manpower and money.

As pharma companies fight to contain rising development costs, improve the efficiencies and higher ROI, integrated label lifecycle management could make a key contribution to some of the industry’s biggest operational goals.

The current scenario

The supply chain journey for clinical trials materials is very complex and variable. Treatments, that comprise various percentages and levels of a drug and placebo, are packaged to be distributed to clinical trial centres for eventual use with trial participants. The packaging and labelling are handled either by the pharma R&D organization itself, the clinical supplies company or a combination of the two. But, with clinical trials now being conducted on a global scale, the ultimate recipient may be located anywhere in the world.

The challenges

In a multi-country, multi-language clinical trial environment, tackling such a comprehensive range of variable data is a huge issue. To achieve the timely, safe and cost-efficient delivery of materials to a global user-base, companies face a number of challenges. Primarily, they must not only ensure that information is presented in the native language of its intended recipient, but they must also make sure that translations – most often from English into a local language – capture the subtleties and nuances of that local language.

In addition, there is also a large amount of local legislation and country-specific label designs. Currently, companies have various systems in place to manage this – some of which are very good – but few, if any, are joined up. As a consequence, pharmaceutical companies need to do more checks throughout the process – with cost implications in terms of time and expense

CTMS system cost totally depends on the vendor your select. average range of CTMS will cost you more than 10,000 dollars the enterprise version.

How do drug manufacturers select the right contract research organization(CRO)?

I am not sure about the selection criteria, but what I think is the reputation of research organization or the departmental heads in research organization play important role in getting contract.

What is the detailed cost breakdown of an expensive clinical trial?

I have read that clinical trials on humans cost millions. I'd like to learn where this money goes as that would help figure out ways of reducing this cost.

Developing a clinical trial budget can be a confusing exercise for sponsors and CROs. There are too many cost variables to account for.

This post covers the key cost drivers for medical device clinical trials. If you are a researcher or financial analyst working in clinical trial space or simply curious about clinical trial costs, this post will serve you well.

So let’s get started.

1. PATIENT GRANT

Patient grant costs are broken down into screening, baseline and follow-up visits and medical imaging costs.

A. SCREEN FAILURES

Clinical trial protocols have inclusion and exclusion criteria to qualify patients. Strict inclusions and exclusion criteria reduce the available patient pool for trial enrollment. Clinical sites spend physician and site coordinator time to screen for potential patients.

During the budgeting process, map out the complete patient screening workflow. Speak with a few clinical sites to understand how many patients they would have to see in order to find one qualified patient. For example, a site may need to screen four patients to find one qualified patient. Understand how many hours the site is spending on screening activities and reimburse accordingly. It is not unusual to reimburse sites anywhere between $50 to $250+ per screen failure.

B. BASELINE/INDEX PROCEDURE AND FOLLOW-UP VISITS

Depending on the clinical trial design, data is collected at baseline/index procedures and follow-up visits. The site coordinator is generally responsible for entering the data in the case report form. Sites are reimbursed for the time spent to collect clinical trial data.

Based on number and type data fields you are collecting, you’ll want to estimate the site coordinator time needed to collect and input trial data. Multiply the estimated coordinator time by the hourly bill rate to obtain the fair market value for each patient visit.

In some cases, sponsors may choose to reimburse patients. Reimbursement for patients can include paying for their participation, reimbursement for travel, meals or overnight hotel stays.

C. NON-STANDARD OF CARE TESTS

Medical device trials may require non-standard of care tests such as medical imaging scans. These costs are generally not reimbursed by insurance companies or medical care agencies and should be budgeted as part of the clinical trial cost.

D. PROCEDURE COSTS

If the clinical trial procedure is reimbursed, you don’t need to budget for the procedure cost. Insurance or medical care agencies will pay for the procedure. In case a brand new procedure where no reimbursement available, budget for the procedure costs.

2. SITE COSTS

A. START-UP FEES

Clinical sites spend significant time to initiate a new clinical trial. Sites are responsible for site specific informed consent development, Ethics Committee (EC)/ Investigational Review Board (IRB) submissions, staff training including participation in investigator/ site coordinator meetings and site initiation visits and execute a clinical trial contract. It is typical for sponsor to pay anywhere between $2000 – $5000+ in site start-up fees.

B. EC/IRB FEES

EC/IRB fees are in addition to site start-up fees. These fees cover the time spent to by EC/IRBs to plan and conduct review of the clinical trial protocol and other associated materials. Many EC/IRBs update and publish their rates annually.

C. CLOSE-OUT FEES

Close-out fees include time spent by site staff to reconcile clinical trial data, finances and regulatory documents during study closure. Not all sites require this payment but has started to become a more common practice in recent years.

D. STORAGE FEES

Government regulations require that clinical trial data be stored after study close-out. The duration for storage can range from 2-years to permanent storage. It is not uncommon for sites to have boxes of regulatory paperwork that needs to be stored once a clinical trial ends. The storage fees vary by country and site.

Some sponsors make arrangements for site to send trial documents to an offsite storage location. Due to country specific regulations, a site might be unable to move documents outside their country.

E. ADMINISTRATIVE OVERHEAD

Clinical sites may require as much as 30% administrative overhead in addition to per patient grant amount. This cost covers management and legal resources needed to provide clinical research oversight and legal review of clinical contracts respectively.

F. SITE MANAGEMENT ORGANIZATION (SMO)

In certain countries such as Japan, data entry and collection tasks are outsourced to SMOs. For post approval studies, sites do not research coordinator support. Sponsors are expected to hire SMOs to support the site or pay the sites to hire their preferred SMOs.

3. NON-PATIENT COSTS

A. CLINICAL EVALUATION COMMITTEE (CEC)

Adverse event and endpoint data is adjudicated by a non-biased, independent CEC. CEC is generally composed 3 or more physicians. CEC members review adverse events and trial endpoints in a team setting or independently.

A sponsor can hire physicians to serve as the CEC and reimburse them at fair market value rates. It is more cost effective for sponsor to contract with physicians directly. However the sponsor has to assign its own resources to manage the CEC.

The other option is for the sponsor to outsource management and conduct of CEC activities. This option is more expensive because you are hiring professionals to manage the CEC.

CEC is a very important component of medical device clinical trial. Adjudicated adverse event data is highly regarded by regulatory agencies and the physician community. In many cases, it is a requirement to have adjudicated adverse event data in order to get the product on market.

B. DATA SAFETY MONITORING BOARD (DSMB)

DSMB is also known as the Data Monitoring Committee (DMC). According to IMARC research, the purpose of the DMC is to advise the sponsor on continuing safety of the trial subjects and those yet to be recruited and provide continuing validity and scientific merit of the study.

For budgeting purposes, it is important to know that DSMB is required during trial enrollment phase and in some cases till all patients have reached their primary endpoint. The decision of whether or not to conduct DSMB meetings after the primary endpoint is reached, is up to the sponsor.

C. PHYSICIAN CONSULTING

Physicians are consulted during all phases of a clinical trial. Physician guidance is needed to develop clinical trial strategy, enrollment plan, final data analysis and publication plans.

Depending on the physician’s medical expertise and geographical location, consulting costs can be anywhere between $150 – $600+ per hour. If a clinical trial is interesting to the physician, he or she may be willing to provide consulting services at no cost.

D. INDEPENDENT CORELAB ANALYSIS

Many medical device trials collect imaging data such as angiograms, CT scans and X-Rays. Since this data comes from multiple sites, variability is expected. An independent corelab standardizes the collection and analysis of imaging data.

Corelab costs can add up quickly. Costs depend upon the number of images analyzed per patient, the time it takes for the corelab to analyze the data, and the duration of the trial.

Corelabs usually hire analysts to collect and calibrate data from different sites. The final analysis is usually done by a physician. Given the complexity of imaging data collection and analysis combined with the importance of corelab data to regulatory agencies, it is important that adequate and accurate budget is allocated for independent corelab analysis.

E. MEDICAL DEVICE COST

Once you are ready to enroll patients in the clinical trial, you’ll need to ship medical devices to the sites. Most sites will expect to receive these devices for free. The only exception is when conducting post approval trials for commercially available devices.

Medical device manufacturers conduct trials for indication expansion. For example, a stent company may conduct a trial to get their heart stent approved for use in a different anatomy. For such expansion trials, sponsors may need to provide commercially available devices to sites at no cost.

Whether or not you want to provide devices at no cost is a business decision. When investigational medical devices are provided at no cost, sites enroll faster and have a much stronger, collaborative relationship with the sponsor.

4. LABOR COSTS

In order to conduct a clinical trial, you need to hire people that have expertise in clinical research and clinical trial management. Depending on the size of the trial and the number of trials conducted, resource allocations vary. Therefore amount of labor needed to run a study also varies.

A. CLINICAL RESEARCH ASSISTANTS OR ASSOCIATES (CRAS)

CRAs are primarily responsible for monitoring clinical trial data that is collected during the course of the study. They visit clinical research sites to ensure data is collected in a compliant manner.

B. PROJECT MANAGER (ALSO KNOWN AS CLINICAL TRIAL MANAGER OR STUDY MANAGER)

A project manager’s responsibilities can vary from one organization to another. Project managers are like “general contractors.” A project manager is responsible for managing the clinical trial budget, resources and timelines. The core function of a project manager is to resolve or escalate issues that come up during the course of a clinical study.

C. DATA MANAGER

A data manager’s job is to address data discrepancy issues by generating queries to sites. Data managers may also be responsible for implementing electronic data capture system or paper case report forms needed to collect trial data.

D. SCIENTIST

The scientist is primarily responsible for developing the clinical strategy for a trial. Individuals with Ph.D. or M.D. degrees are usually the right fit for this role. In some organizations, the project manager also play the role of the scientist.

E. BIOSTATISTICIAN

A biostatistician is responsible for developing a statistical analysis plan (SAP). The SAP documents on the data will be analyzed during the course of the study. A statistician or statistical programmer is also responsible for programming data tables that are incorporated in the final clinical study reports.

F. QUALITY

Clinical research is a regulated industry. Quality plays an important role in ensuring sponsors, CROs, and clinical sites are conducting the trial in a compliant manner. A quality associate or manager helps an organization create and implement standard operating procedures (SOPs).

Salaries for these roles can vary by geography and experience. The above list is not comprehensive. However it should give you an idea of the core resources needed to conduct a medical device clinical trial.

5. SITE MANAGEMENT

A. PRE-STUDY VISITS

Prior to inviting any site to participate in a clinical trial, you want to conduct pre-study visit, also know as the site assessment visit. This visit becomes even more important if you don’t have any prior experience working with the site in a clinical or commercial setting.

Although sites don’t charge for this visit, the sponsor will need to pay for travel and CRA labor costs.

B. SITE INITIATION VISITS (SIV)

Once the site has received Institutional Review Board (IRB) approval and the trial contract has been signed, it’s time to activate the site for patient enrollment.

A SIV is conducted once you are ready to activate the site. SIV involves training the site on the clinical protocol and any other study-specific requirements.

Similar to the a pre-study visit, the sponsor will need to pay for travel and CRA labor costs.

C. MONITORING

Once patients are enrolled in the study, you want to ensure data is collected in a compliance with regulations and the clinical study protocol. This is when monitoring comes into play.

A CRA, sometimes known as the site monitor, visits clinical sites at regular intervals to ensure compliance.

In recent years, due to push for reduction in clinical trial costs, several sponsors have started to monitor remotely rather than conducting an in-person monitoring trip.

D. CLOSE-OUT

Once all patients at a site have completed their follow-up visits, it’s time to conduct a close-out visit. Any open items related to study conduct are addressed during the close-out visit.

Although it’s always nice to have in-person close-out visits, it’s acceptable to close trials via remote close-out calls.

6. MISCELLANEOUS

A. INVESTIGATOR MEETINGS

Investigator Meetings usually serve to kick-off a new clinical trial. Investigators and research coordinators participating in the study are invited to participate in a 1-2 day meeting. The purpose of these meetings is to educate site personnel on the clinical trial protocol and any other specific trial requirements.

These meetings can be quite expensive as airfare, hotel and meals are usually provided by the sponsor.

B. TRAVEL

Plan and budget for adhoc travel. Since clinical trials are heavily regulated, you may need to visit a site to address a compliance issue or help them prepare for an audit. In other cases, you may want to visit a site to motivate them to enroll patients. Whatever the case may be, it’s always good to have some money set aside for travel.

C. DOCUMENT TRANSLATIONS

Document translations costs can increase significantly depending on the countries in which the clinical trial is conducted. Sites where English is not the primary language, you may receive request for translation of key documents such as the protocol and site specific informed consent in the local language.

Also if the adverse event source documents from non-English speaking sites are in their native language, additional costs will incur to translate documents into English for event adjudication purposes.

D. TECHNOLOGY SOLUTIONS

Clinical Trial Management System (CTMS), Electronic Data Capture (EDC), Electronic Trial Master File (eTMF), Interactive Voice/Web Response System are a few common technology solutions implemented when conducting a clinical study. These systems are needed to manage site contact information, collect clinical data and maintain clinical trial records. There is a monthly or annual license fee associated with these systems. Additionally staff is needed to manage and maintain these systems.

E. REGULATORY FILING FEES

Regulatory filing fees should not be overlooked as these can run into thousands of dollars. Depending on the class of medical device, different applications need to be filed with regulatory agencies, competent authorities and notified bodies.

7. OTHER FACTORS:

A. PROTOCOL AMENDMENTS

Due to unforeseen circumstances, a clinical protocol amendment may be necessary. A protocol amendment has many downstream effects that can increase the cost of a clinical trial.

A protocol amendment usually leads to additional IRB/EC fees, site costs, regulatory re-submissions and more.

B. INFLATION, VALUE ADDED TAX (VAT) AND FOREIGN EXCHANGE

Inflation should be factored in for multi-year clinical trials. In the US, a minimum 3% inflation is expected.

Sites in countries such as Australia and Europe, add VAT for the research services. VAT can be upwards of 12% on all research services.

For trials conducted in multiple countries, paying attention to foreign exchange rates. At a minimum, annual review of exchange rates is advised. Clinical trial cost projections should be adjusted based on exchange rates.

C. TRIAL ENROLLMENT DELAYS

Enrolling in trials is tricky business. It takes longer to complete enrollment and initial projections are overly optimistic. Account for these delays when you develop your clinical trial budget.

[1]

To summarize, you should now have a solid understanding of these factors that impact clinical trial costs:

• Patient grant amount such as screen failure costs, data entry costs and travel reimbursement
• Site costs such as site start-up fees, EC/IRB fees, close-out and storage fees
• Non-patient costs such as core labatory fees, clinical events committee and data safety monitoring board
• Labor costs – clinical research employee salaries or contractor payments
• Site management costs such as pre-study, site initiation, monitoring and close-out visits
• Miscellaneous costs such as travel, technology solutions and regulatory filing costs
• Other factors such as value added tax, inflation, protocol amendment and delays in enrollment

Footnotes

[1] Ultimate Guide to Clinical Trial Costs - Clinical Trial Podcast

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Adithya Balasubramanian, As confused as everyone.

Updated Jun 11, 2013 · Upvoted by Kate Simmons, myofascial pain specialist and David Chan, MD from UCLA, Stanford Oncology Fellowship

My entire answer to this question is from

http://www.manhattan-institute.o....

In 1975, the pharmaceuticals industry spent the equivalent of $100 million in today’s dollars for research and development of the average drug approved by the U.S. Food and Drug Administration, according to the Tufts Center for the Study of Drug Development. By 1987, that figure had tripled, to $300 million. By 2005, this figure had more than quadrupled, to $1.3 billion.

The true amount that companies spend per drug approved is almost certainly even larger today. Matthew Herper of Forbes recently totaled R&D spending from the 12 leading pharmaceutical companies from 1997 to 2011, and found that they had spent $802 billion to gain approval for just 139 drugs: a staggering $5.8 billion per drug.
The biggest driver of this phenomenal increase has been the regulatory process governing Phase III clinical trials of new pharmaceuticals on human volunteers. One reason: Phase III clinical trials have become far larger and more complex than they were in the past. From 1999 to 2005, as the Tufts group has shown, the average length of a clinical trial increased by 70 percent; the average number of routine procedures per trial increased by 65 percent; and the average clinical trial staff work burden increased by 67 percent. On top of that, increasingly stringent enrollment criteria and trial protocols resulted in 21 percent fewer volunteers being admitted into trials and 30 percent more enrollees dropping out before completion of the tests.
Overall, Phase III trials now represent about 40 percent of pharmaceutical companies’ R&D expenditures. But this often-cited statistic actually understates the gravity of the burden. This is because overall R&D expenditures include all pharmaceutical candidates that a company tests—including hundreds that never reach the Phase III trial stage. When we confined our analysis to those drugs that actually get approved, we found that Phase III clinical trials typically represent90 percent or more of the cost of developing an individual drug all the way from laboratory to pharmacy.
In this paper, we look at four particular areas of public health concern: obesity; diabetes; stroke and heart ailments; and “orphan diseases” (ailments that afflict very small populations and hence lack the normal market incentives to develop treatments). We analyzed the progress of 12 major new pharmaceuticals developed across these four categories and found that in nearly every case, Phase III trials represented at least 90 percent of the entire cost of a drug’s development.

This cost burden creates a system of perverse incentives for researchers and industry, which discourages the rational allocation of resources for drug development. After all, only one in 12 drugs that enter human clinical trials end up gaining approval from the FDA. This risk profile has led smaller companies to go bankrupt when they have faced setbacks in clinical studies. Many private investors are withdrawing venture capital support for start-up drug companies, fearing that their investments will vanish if there is the slightest hiccup in the development process.

The consequences for Americans are higher-than-necessary health spending and poorer health outcomes. Pharmaceutical companies charge more for their products, in order to recoup their costly and risky investments. And fewer beneficial drugs reach doctors and patients.
What Is a Phase III Trial?
Federal law requires that medications proposed for human use go through “adequate and well-conducted clinical trials.” Around this statutory language, regulations and standardized practices have built a three-phase system for any compound that, having emerged from basic research and animal testing, is deemed a candidate for pharmaceutical use. These three stages (paid for, of course, by the medicine’s developer) begin with Phase I trials, involving perhaps 100 people at most, to assess the proposed drug’s safety and whether it works in treating a particular condition, symptom, or illness. If the medication “passes” these tests, it moves on to Phase II trials, which assess how well the drug works as well as how safe it is, and they involve a larger number of people (100–300).
Only after these stages does a drug candidate move on to Phase III trials, which test the drug against placebos, as well as currently available treatments, on thousands of people. The large sample size is essential to uncovering potential side effects that may affect small percentages of people and therefore may be missed in the smaller trials. Large-scale trials also protect against statistical accidents that often occur in small samples and thus provide a more complete and reliable portrait of the drug’s benefits and risks.
The importance of Phase III trials stems from the statutory language in the Federal Food, Drug, and Cosmetic (FD&C) Act. Under Section 505(d) of the act, sponsors of new drug applications must demonstrate “substantial evidence” of the drug’s clinical benefit, with “substantial evidence” being defined as “adequate and well-controlled investigations … by [qualified] experts.”
Under the FD&C Act, the FDA has considerable discretion to determine what constitutes “substantial evidence.” The agency has interpreted the plural form of the word “investigation” in the statute to mean that companies must sponsor at least two such studies, and those studies are usually large, multiyear Phase III trials—the ones that swallow up so much private capital. By tradition, each of these trials is expected to show, with 95 percent statistical certainty, that a drug meets its tested aims of clinical benefit.
Phase III Trials Are the Biggest Driver of the Rising Cost of Innovation
In order to more accurately estimate the contribution of Phase III studies to the cost of drug development, we reviewed public filings and records for companies developing medicines in four areas: GLP-1 inhibitors for diabetes; factor Xa inhibitors for cardiovascular disease; several new drugs for reducing obesity; and medications for several rare disorders such as Hodgkin’s lymphoma.
We calculated the number of patients studied in every clinical trial that the selected companies sponsored. We then cross-referenced these data with the average per-patient cost of clinical trials, as reported by a 2011 survey by the medical management consulting firm Cutting Edge Information. These are the data that show that, in most cases, companies spent more than 90 percent of their development money per drug on Phase III clinical trials. In the field of obesity, the average was 91 percent; in diabetes, it was 93 percent; in cardiology, it was 94 percent. Only among rare disorders were there exceptions to the general rule because in that field, some companies can take advantage of the FDA’s accelerated approval process and forgo Phase III studies.

http://www.manhattan-institute.o...

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Darshan Kulkarni, Certified in Clinical trials by the Temple University School of Pharmacy. I work with CROs, Sites and Indus...

Answered Mar 7, 2012

There is no reasonable way to answer that question with specifics. Specific costs will vary based on the goal of the studies. Nevertheless, some of the costs may include: hiring a CRO, a CRO hiring sites both locally and globally, contract negotiators, statisticians, doctors, nurses, pharmacists, managers, CRAs etc. You are literally talking about hundreds to thousands of people that may be involved, each performing a specific task.

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This answer is not a substitute for professional legal or medi... (more)

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Ryan Jones, Healthcare data guy

Answered Dec 30, 2014

That Manhattan group posted is pretty good. As a compliment this online book has the best overview I've seen: Discussion Paper

We have a summary of these costs issues in our latest post, too:
http://blog.florencehc.com/

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Raphael Miyashiro, Startup Specialist, Clinical Trials

Answered Mar 24, 2016

I just want to bring a simple report  from EFPIA (European Federation of Pharmaceutical Industries and Associations), wich states that it cost aproximately 1506  million dollars to bring a new chemical to the market (2012)

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Nicole Gomez, is a professional Trainer at PWAC Business Solutions. PWAC Business Solution provides employee training and...

Answered May 29, 2014

It depends upon what kind of trial research one wants to set up. If the goal provides long term results than it may cost more compare to the short term clinical trials that need to be conducted.

It is certainly not cheap to bring a new drug or treatment to market-- it can cost about $1.5 billion and takes 8 years on average. That being said, clinical trials also provide a significant economical and lifestyle benefit. In Alabama for instance, clinical trials and associated medical research have certainly become a significant part of the economy-- supporting more than 17,000 jobs! Here's a really interesting article that goes more in-depth on the subject: How Have Clinical Trials Improved Life in Alabama?

What's the average clinical trial startup time?

I define clinical trial startup as the process of identifying and activating clinical trial investigative sites, culminating in "first patient in"

You won’t believe it, but I’ve had studies where start-up lasted for more than a year for certain sites. This was due mostly to a highly ineffective LEC (IRB), long contract negotiation process and lack of involvement by the PI. Having mentioned these three key risks, you’d think the site wouldn’t be selected for participation, but then if the PI is a KOL, or there is a large patient population, all you can do is be upfront and transparent about risks and document every single contact. Usually, these sites either never get off the ground or finally have all approvals in place when recruitment is closed before they even have a chance to enroll their 1st patient.

I’ve also worked on a study where the start-up phase was 2 years. This was for an extremely rare indication in toddlers where the subjects were so rare they were brought in from other countries to participate. So in this case, protocol development, study logistics was 1 year and then review by ethics committee & organizing enrollment the 2nd year.

Six to nine months, depending on how quickly the sponsor can approve the contract and the consent wording, and whether or not the IRB requires a second full-board review.

depending on the trial size, the indication and the experience of the company running it.I would go with 6 months but it can easily spill into the 9-month frame for large Phase IIIs (although many sites will have been identified from Phase II)

A CRO may do all:

• Epidemiological surveys
• Clinical trials