The United States has consistently emerged as a leading site for clinical research.
Clinicaltrials.gov registry, which serves as an effective reference to see clinical trials conducted worldwide, provides an interesting statistics regarding U.S. clinical trials.
Clinical trials statistics in the U.S.
- A glimpse into the studies registered between 2011 and 2013 and further between 2014 and 2016 shows that the U.S. and Western Europe are the major hub for clinical trials.
- U.S. had the highest number (33.3%) of registered clinical trials in 2014-2016 and was followed by France (8.5%), Canada (5.9%), United Kingdom (5.7%) and Germany (5.4%).
- Together, these countries are located in the traditional regions of North America and Western Europe, hosting 58.8% of all clinical trials (44,370[sum of five countries]/75,420 [total number of clinical trials]). Except for the U.S., each country contributed 5%-9% to the total number of clinical trials.
Leading global pharmaceutical companies conduct majority of their clinical trials in the U.S. and in Western Europe. They find several compelling reasons to do so.
- Availability of thousands of qualified, inspected and verified investigators
- Robust and easy regulatory system in place
- Great professional clinical research culture
If you’re looking to conduct clinical trials in such a place with great emphasis on quality and timelines, U.S. might be the region you’re looking for. Here are several things to consider, when you start planning to conduct clinical trial in US.
Of course, the first things to consider are the regulatory requirements and necessary approvals.
U.S. Regulatory situation for Clinical Research
Conducting clinical studies in the U.S
- An investigational new drug (IND) application is usually submitted to propose clinical investigation of an unapproved drug, or an approved product for a new indication or in a new patient population.
- IND is also required to conduct a bioavailability or bioequivalence (BA/BE) study if the test product contains a new chemical entity or involves a radioactively labeled drug product or a cytotoxic drug product.
- The U.S. FDA responds to a IND application within 30 days, if it has any concerns (Clinical Hold). In that case the sponsor has to respond to the queries and can start the study only after a written notification from the FDA to do so.
- In case there is no response from the FDA in the 30 day window period, the sponsor can start the clinical development program as described in the IND on 31st day provided institutional review board (IRB) approval is in place.
Figure depicts an overview of the conduct of clinical studies for marketing approval in the U.S.
Supportive regulatory framework for generic products
- The Hatch-Waxman Act, 1984, provides a supportive framework to the generics industry and the resultant competition to their brand counterparts.
- By abbreviating processes and reducing sponsor cost, the generics market has grown to account for nine out of 10 prescriptions dispensed in the U.S. today.
- The 505(j) is the approval route for generics.
- BA/BE studies using unapproved versions of approved drug products can be conducted without submission of an IND [21 CFR 320.31(b) and (d)].
- BA/BE studies must comply the requirements for review by an IRB (21 CFR part 56), informed consent (21 CFR part 50) and retention of test article samples (21 CFR 320.31(d)(1)).
- Further 505(b)(2) NDA is like an hybrid between the full application 505(b)(1) NDA and the 505(j) ANDA. [NDA- New drug application; ANDA- Abbreviated new drug application]
- The provisions of 505(b)(2) allows some information required for NDA approval, to come from studies not conducted by or for the applicant. This has greatly reduced the cost to the sponsor and allowed for a faster route for drug approval.
Speeding up the clinical development program
- The FDA encourages all potential drug sponsors to utilize the Pre-IND Consultation Program.
- This can be used to discuss the drug development path and suitable regulatory pathway for marketing authorisation upfront with the FDA.
- A sponsor may simultaneously apply for IRB approval of the protocol(s) mentioned in the IND.
- As required by 21 CFR 56.106, IRB in the U.S. that reviews FDA-regulated studies should be registered with the Office for Human Research Protections (OHRP).
- IRB registration information is maintained by the Department of Health and Human Services (HHS). There are more than 10,000 IRBs that are registered with the OHRP IRB registration system.
- A sponsor may seek IRB approval before an IND application however recruitment and enrollment does not begin before both effective IND and IRB approval are secured.
Shipment of clinical trial drug product
- The sponsor may want to transport or distribute the clinical study drug across the state borders. However according to the current U.S. federal laws, only drug with marketing approval can be transported or distributed across state lines.
- An IND application provides an exemption to this law.
- It is only required that such product intended for human use should be labeled with the statement “Caution: New Drug–Limited by Federal (or United States) law to investigational use.”
If you’re familiar with the regulatory requirements and are confident to be able to comply with them, next thing to consider are the availability of sites and investigators in United States.
Site and Investigators in the U.S.
Investigators in US are some of the most informed, experienced, qualified and willing to perform investigators in the world. It also helps that they work in one of the most advanced countries.
Therapeutic areas available
United States is home to patients from a number of therapeutic areas ranging from some of the common ones like oncology to even rare indications like Acute unilateral vestibulopathy.
As per an article published in 2013 ( https://www.ncbi.nlm.nih.gov/pubmed/23842577 ) on disease burden in the U.S. , diseases with the largest number of YLLs (Years of life lost due to premature mortality) in 2010 were ischemic heart disease, lung cancer, stroke and chronic obstructive pulmonary disease. While, diseases with the largest number of YLDs (Years lived with disability) in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders; neuropsychiatric disorders are now considered as the leading cause of disability in the U.S., followed by cardiovascular and circulatory diseases and neoplasms (https://www.nimh.nih.gov/health/statistics/disability/us-leading-categories-of-diseases-disorders.shtml).
If one is looking for investigators for clinical trials in oncology, cardiovascular diseases, metabolic diseases like diabetes, psychopathic disorders, neurology and other leading disorders listed above, U.S. can be a great place to go to.
Credevo has access to most of these therapeutic indications and clinical trial investigators in United States. It’s possible to get access to them by signing up and posting a project requirement on Credevo.
Numbers of sites and investigators
As per a book from NIH (https://www.ncbi.nlm.nih.gov/books/NBK50886/) published in 2010, total number of investigators in United States was 14000, although this seems to be the figure for clinical trials active at that time. The number has shown to be more based on the trials posted on clinicaltrials.gov.
Credevo has access to about 25000 investigators in U.S. These investigators work in about 40 therapeutic segments and come from sites managed by their own team or by another site management organizations. Some of the sites are quite well managed and work in a group of few to more than 1000 per site.
Start feasibility process on Credevo and get connected to these sites.