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The development of medical device starts with the need realized by a physician or surgeon. The device development is usually the result of this need and communication between him and engineer from a medical device supplying company. Although large medical device companies typically develop successive iterations of existing devices, most new device categories are typically developed by venture-backed start-up companies. Typically, a physician and/or engineer inventor conceives of a device solution to an unmet clinical challenge, initiates the patent process, and builds preliminary device prototypes. Preliminary bench and animal testing may be performed using the inventor’s or an acquaintance’s personal funding (angel investors). Further development typically requires engaging a team of engineers who work closely with physician advisors to bring the concept through the “design-build-test-redesign” cycle of bench and animal testing. This preclinical stage typically takes 2 to 3 years and depending on the nature of the device may consume US$10 to $20 million before the device is ready for clinical testing. These capital requirements exceed the means of most angel syndicates and are typically obtained from venture capital firms in the form of equity financing.A small percentage of device ideas are conceived in academic medical centers using federal or other grant funding. Few academic centers have the intrinsic capabilities to develop the device beyond the early prototype stage. Intellectual property is typically out-licensed to an existing company or start-up for further development. To facilitate the development of ideas that emerge out of federally funded programs, Congress passed the Bayh-Dole Act that assigns all intellectual property rights to the academic medical center.Initial Clinical TestingA start-up company’s survival is dependent on reaching milestones efficiently (in terms of time and money) to successfully raise additional funding. First clinical use is perceived by many as a key milestone, so that delays in the initiation of clinical testing programs can threaten a company’s viability. Companies will therefore seek the quickest path to first clinical use. US regulatory requirements are more extensive and require additional time and resources compared with those of other countries. It is estimated that obtaining Food and Drug Administration (FDA) approval to initiate clinical studies in the United States adds 3 to 6 months to the process of device development. In addition, subsequent review by the institutional review board (IRB) at the clinical site can add an additional 3 to 6 months to this timeline. Because of these factors, initial clinical device testing has shifted largely to outside of the United States. It is thus estimated that more than 75% of first clinical use cardiovascular device testing is now outside the United States, saving what may be 6 to 12 months when compared with US clinical initiation. When initial clinical testing is performed within the United States, it is estimated that only 25% of the work occurs at academic institutions. This is due in part to the bureaucracy associated with large academic institutions for both IRB approval and contract negotiations .Clinical testing of an unapproved significant-risk medical device requires FDA approval in the form of an Investigational Device Exemption (IDE). The IDE application provides information to the FDA on device design and qualification, as well as on the study protocol. The FDA is mandated to respond to the IDE application within 30 days.1 An IDE may also be required for studies in which an approved device is used for a purpose distinct from its approved indication.2 This is typically the case when a trial is sponsored by a company for the purpose of expanding the indication of a device or making significant changes in the instructions for use.Regulatory Approval Process (United States)Medical devices are regulated in the United States by the Center for Devices and Radiological Health (CDRH) of the FDA. The FDA/CDRH mandate is to promote and protect the public health by making safe and effective medical devices available in a timely manner. The standard for demonstrating safety and effectiveness is determined in part by the risk associated with the device in question. Devices are classified according to their perceived risk using a 3-tiered system (class I, II, or III).Class I devices (lowest risk) are subject to general controls, which are published standards pertaining to labeling, manufacturing, post-market surveillance, and reporting. Devices are placed into class I when there is reasonable assurance that general controls alone are adequate to assure safety and effectiveness. The general controls that typically apply to class I devices include prohibitions against adulteration and misbranding, requirements for establishing registration and device listing, adverse event reporting, and good manufacturing practices. Furthermore, remedies including seizure, injunction, criminal prosecution, civil penalties, and recall authority are provided to FDA. Formal FDA review is not required for most class I devices before their market introduction.Class II devices are those higher-risk devices for which general controls alone have been found to be insufficient to provide reasonable assurance of safety and effectiveness, but for which there is adequate information available to establish special controls. Special controls may include performance standards, design controls, and post-market surveillance programs. In addition, most class II devices require FDA clearance of a premarket notification application (PMA or 510[k]) before the device may be marketed. In the 510(k) application, the medical device manufacturer must provide data to demonstrate that the new device is “substantially equivalent” to a legally marketed device. Although substantial equivalence can usually be demonstrated on the basis of bench and animal testing alone, approximately 10% of 510(k) applications include clinical data.Class III devices, such as heart valves, pacemakers/implantable cardioverter-defibrillators, and coronary stents, are judged to pose the highest potential risk. These devices are either life-sustaining/supporting, of substantial importance in preventing impairment of human health, or present a high risk of illness or injury. Consequently, general and special controls alone are inadequate to provide reasonable assurance of safety and effectiveness. Most class III devices require FDA approval of a PMA before they can be legally marketed. Approval of the PMA generally requires clinical data demonstrating reasonable assurance that the device is safe and effective in the target population.The Human Device Exemption (HDE) is a new pathway to allow for commercialization of class III devices designed to address small markets, ie, diseases or conditions that affect fewer than 4000 patients in the United States each year. Approval of an HDE requires demonstration that the device is safe and the probable benefits outweigh the probable risks. Although the process may require smaller clinical trials, an HDE device must continue to operate under local IRB approval at each participating institution and must continue to collect case report forms akin to an ongoing clinical trial. The PMA process typically involves a series of studies starting with first clinical use and culminating in a multicenter, prospective randomized control trial (pivotal trial). The complexity and extent of the clinical testing program is dictated by the nature of the device and its proposed use. The clinical study program is developed by the company in conjunction with clinician investigators, all in close collaboration with FDA/CDRH.The first and arguably most important step in this process is the pre-IDE meeting, in which the company, often accompanied by the lead clinical investigator(s), meets with FDA/CDRH to present data about the device, its clinical development program, and its intended use after approval. The FDA/CDRH staff reviews existing bench and animal data (as well as any outside-the-United States clinical data) and makes informal non-binding suggestions regarding the need (if any) for additional pre-clinical data (bench and animal), as well as the study design. The sponsor then submits an IDE application to FDA/CDRH (Medical Devices) for formal review.Clinical development of a new class III device is typically divided into pilot and pivotal trial phases. The purpose of the pilot phase (starting with first clinical use) is to establish safety and to assist in design of the pivotal trial. Pilot-phase testing is typically limited to fewer than 100 patients treated at a few centers. The purpose of the pivotal trial is to generate data that define patient populations in which use of the device is safe and effective. The dialogue initiated during the pre-IDE meeting continues and intensifies between FDA/CDRH and the company over the specifics of the pivotal trial and includes the patient population, the control group against which the new device will be evaluated, and the primary and secondary end points of the evaluation. For first-in-class devices, eg, drug-eluting stents, where there are few data regarding short- or long-term outcomes, FDA/CDRH requires prospective randomized controlled studies. Though high profile, devices that require randomized data for approval are the exception rather than the rule. The vast majority of device clinical trials are case series that carefully document product performance. Still more products are approved as “tools.”Most devices currently in testing are similar to well-characterized approved devices, eg, next generation bare metal stent, angioplasty balloon, etc. When FDA/CDRH has substantial data on the device class metrics, comparisons may be made to historical data or objective performance criteria. When few data on existing standards are available, the FDA typically requires randomized rather than single-arm studies, in which the new device is compared against concurrent controls treated with current best medical practice. That comparison may be powered to show that the new treatment is superior to prior approaches, or that it is non-inferior (equivalent or better) compared with a previously approved device in a new area. The issues relating to the type of trial are discussed below.The specifics regarding study design may have profound impact on the time and cost of bringing a new device to market. Though the primary mission of the FDA/CDRH is to ensure safety and effectiveness of commercially available devices, when exerting regulatory oversight the agency must balance its primary mission with the costs of introducing new technologies to the clinical marketplace. This has been codified by the FDA Modernization Act and the FDA Modernization Act-II, which require the agency to pursue the “least burdensome means” available to establish device safety and efficacy. Although surrogate end points, eg, angiographic restenosis rather than recurrent cardiac events, may be allowed as secondary end points, the primary end point of a pivotal trial for a first-in-class class III (Classify Your Medical Device) device is usually a clinical end point (or a well-established surrogate such as infarct size in a myocardial infarction treatment device). Depending on the end points negotiated, such pivotal trials may require enrollment of 1000 or more patients at 30 to 50 sites over a period of 1 to 2 years, with appropriate follow-up frequently to 1 year after treatment. The trial must be conducted according to good clinical practices standard, with the approval of the local IRB at each participating center.Clinical Site (IRB, Contract, Conflict of Interest)Once the FDA/CDRH has approved the IDE, the sponsor must formally recruit as many as 50 sites to ensure patient enrollment in a timely fashion. Each site has its own rules regarding participation in clinical studies, which typically can be divided into 3 components: Human research, contract, and conflict of interest.Every clinical site is federally mandated to have an IRB responsible to ensure the protection of the rights, safety, and welfare of research subjects. Regulation of the IRB review of protocols involving medical devices is under the purview of the FDA. The Office of Protection From Research Risks (OPRR) is responsible for oversight regarding all human research and is in direct communication with the FDA/CDRH. Studies involving human subjects that do not involve products regulated by the FDA fall under the direct purview of the OPRR. Both the FDA and the OPRR are in the Department of Health and Human Services. Each IRB must meet standards for the composition, leadership, and processes set forth by that department. IRBs are subject to periodic audits by the FDA to ensure that records and procedures are in compliance with regulations.Working with the sponsor, the principal investigator prepares an application to the IRB at his/her institution that includes the consent form describing in lay language the device, the proposed clinical study, the inclusion and exclusion criteria for the trial, and a draft consent form describing the risks and benefits of participation in the study. The IRB then formally reviews the application and frequently requests changes, particularly to the informed consent. The IRB process typically requires approximately 3 months, but at times can take considerably longer.The company must also negotiate agreements with each clinical site addressing the many issues associated with the clinical trial. In addition to the study costs/reimbursement (per-patient enrolled and overhead), these agreements typically include indemnification and the assignment of ownership rights of new discoveries (intellectual property) made in the course of the study. The resources required at each center to perform the high quality research necessary for a PMA protocol are formidable. In addition to resources required to maintain an excellent clinical program (physician, nursing, and technical staff coupled with state of the art facility), the study center must dedicate additional resource, primarily research nurses to perform high-quality clinical research. The role of the research nurse is critical to all phases of the trial, including general study management, IRB process, patient recruitment, and accurate completion of case report forms. The sponsor is responsible for accrediting each clinical site to document that the necessary resources are in place to fulfill the demands set forward in the protocol. The clinical research staff do not provide clinical care and are thus not part of the hospital’s salaried clinical nursing staff. The per-patient costs include all additional charges the patient incurs for the study, including procedures (therapeutic and diagnostic), clinic visits, and diagnostic studies, as well as research nurses’ salaries. It is estimated that it takes 3 to 6 months to formally recruit each clinical site.Device development from the earliest stages requires active involvement of practicing clinicians. Clinician/inventors are frequently involved in creation of the device concept and are often integral members of the design team performing the majority of the early animal studies. Through this involvement, the clinician/inventor obtains intimate knowledge of device performance and failure modes. Safety concerns during first clinical use and pilot phase mandate participation by these clinician/inventors. The clinician/inventors frequently take leadership roles and have equity positions in the company developing the device. These interests present important conflicts of interest which must be addressed to ensure patient safety, data integrity, and public trust in the process. Many institutions have set up formal processes to address these conflicts of interest, potentially adding more time to the institutional recruitment process.Pivotal studies required for a PMA application are typically large multicenter randomized trials and often represent the largest commercial risk and expense in the device development process. In addition to obtaining an IDE from the FDA and formally recruiting clinical sites, the sponsor must also put into place an extensive infrastructure that typically includes engaging a contract research organization (CRO), core laboratories, formation of a data safety monitoring board (DSMB), and an executive committee. The CRO provides the infrastructure required to recruit, qualify, and audit sites. Core laboratories evaluate primary data, eg, angiography, ECG, and ultrasound results, in a uniform and blinded manner. An executive committee is typically composed of the clinician investigators, company representative, CRO, and core laboratories. The DSMB, composed of a group senior clinical investigators and statisticians with no other involvement in the study, periodically reviews trial data at specified intervals. The DSMB has the mandate to stop or modify a study, eg, discontinue randomization to one of the groups if complications associated with the study device are in excess of anticipated rates, if differences between study groups reach statistical significance, or if further patient enrollment will not impact study outcome.Regulatory Approval Process (European Union)Though there are many similarities in the regulatory process in the United States and countries within the European Union, there are important differences that impact the time and cost associated with the introduction of a new medical device.I have identified 3 illustrative examples: Use of notified bodies, criteria for approval, and local site (IRB/site negotiation).The European Union system relies heavily on notified bodies (NBs), which are independent commercial organizations to implement regulatory control over medical devices. NBs have the ability to issue the CE mark, the official marking required for certain medical devices. NBs are designated, monitored, and audited by the relevant member states via the national competent authorities. Many functions performed by the FDA/CDRH within the United States are performed by NBs, including medical device certification, device type designation, assessment and verification of quality systems, and review of design dossiers for high-risk devices. Currently, there are more than 50 active NBs within Europe. A company is free to choose any notified body designated to cover the particular class of device under review. After approval, post-market surveillance functions are the responsibility of the member state via the competent authority. NBs typically function in a closed manner, providing little visibility on criteria required for approval. This dynamic allows for a high degree of variation as well as competition among NBs. As a result, NBs are perceived by industry to be less bureaucratic organizations that can respond more quickly and efficiently than the FDA. These potential benefits may be offset by a system that is intrinsically more fragmented and highly variable and has resulted in the approval and continued marketing of devices, eg, abdominal aorta stent grafts, in Europe that failed efficacy trials in the United States.Criteria for approval of high-risk devices are different in the European Union. To receive approval to market a class III high-risk (and some class II) device in the United States, the manufacturer must demonstrate the device to be reasonably safe and effective, which typically requires a prospective, randomized controlled clinical trial. To receive approval to market a device in the European Union, the manufacturer must demonstrate that the device is safe and that it performs in a manner consistent with the manufacturer’s intended use. This difference has a profound impact on the size and scope of the clinical studies for regulatory approval. This significant difference is illustrated by examining the introduction of distal protection systems. The GuardWire developed by PercuSurge, Inc (later acquired by Medtronic) is a specialized coronary guidewire with an elastomeric balloon mounted at the tip. During an angioplasty/stent procedure, the operator crosses the lesion with the GuardWire and inflates the balloon. Stent placement is then performed, after which a specialized catheter is used to evacuate any arterial debris that may have become dislodged during the procedure. The GuardWire balloon is then deflated. Demonstration of safety and performance, ie, ability to aspirate material during the stenting procedure, was demonstrated in a 22-patient single-arm study. In contrast, in the United States, this device was designated class II (requiring 501[k] clearance and clinical data). To satisfy US criteria for clearance, the standard of safety and effectiveness required in this case was defined as the ability to reduce complications associated with stenting of saphenous vein grafts. To meet this criterion, an 800-patient multicenter trial randomized trial comparing distal protection to usual care (no protection) was performed. At 30 days, a 42% relative reduction in major adverse cardiac events (primarily myocardial infarction) was observed. A trial of this type is estimated to cost US$10 to $12 million and may take 24 months to perform.

Tuition OverviewAll Saints University College of Medicine offers one of the most affordable medical school tuition fee structures.The breakdown of fees for the 4-Year and 5-Year MD programs are outlined below. All fees listed are in US Dollars.Students pay a one-time non-refundable application fee of $100 and a one-time non-refundable enrollment fee of $1000. There is, additionally, a non-refundable health insurance fee of $100 per semester. All students are responsible for their own lifestyle expenses (e.g., transportation, lodging, books, etc.)CLINICAL SCIENCES: ***Please note that certain premium placement clinical clerkship rotations have higher costs associated with their placement. These placements are offered to certain students at the discretion of the University, depending on available space, student academics, eligibility and other determining factors.*SCHOLARSHIPSAll Saints University, College of Medicine, St Vincent and the Grenadines offers partial scholarships based on the academic qualifications, personal experiences and financial need of the applicant.After you submit your application online our admissions office will review your grades, essay and recommendation submitted to see if you qualify for a scholarship. Our admissions department will look for strong grades in the sciences (biology, chemistry, physics, math) but will also review your essay and recommendation letters before they make their decision.Each applicant’s completed application and supporting documentation is reviewed by the Admissions Committee before a final decision is made regarding scholarship. Students who are granted scholarships must maintain the criteria established by the Office of Academic Affairs every semester to continue holding the issued scholarship. Failure to upkeep the criteria will results in a loss of scholarship. Scholarship applicants must maintain a 80% or above attendance and remain in good academic and financial standing and be free of any disciplinary actions with the University.Local and International students are eligible for consideration for a scholarship from the University. Successful applicants will receive a scholarship letter, which they must sign and return to the Admissions Office in order to accept the terms of the scholarship and have it applied to their account. Part time students are not eligible for scholarship consideration.RICHMOND GABRIEL ACADEMIC SCHOLARSHIPThe Richmond Gabriel Scholarship is based on academic merit and personal experience. It is 35% off the tuition fee for the Undergraduate and Basic Medical Sciences program and 10% off the tuition fee for the Clinical Clerkship program. In addition to meeting all the standard admissions criteria, students should be enrolled on a full-time basis to be considered for the Richmond Gabriel Scholarship.ADDITIONAL ACADEMIC SCHOLARSHIPSStudents with an exceptional academic record are eligible for additional academic scholarship for the Undergraduate and Basic Sciences components of the MD degree program. Academic scholarships are based on the CGPA of the admission prerequisite courses for the program to which the student is applying.ST. VINCENT GOVERNMENT SCHOLARSHIPAll Saints University, College of Medicine, St Vincent and the Grenadines, in collaboration with the Government of St. Vincent and the Grenadines, offers limited full scholarships to qualified applicants. Students must meet the criteria for admissions and maintaining their scholarships. Failure to meet the criteria established by the Office of Academic Affairs for Scholarship holders will result in a loss of scholarship.BILLING INFORMATIONStudents will receive an invoice from the Accounts Department 30 days prior to the beginning of the new semester. Invoices should be paid upon receipt or before the commencement of classes. If a student does not receive an invoice during this period, s/he should contact the Accounts Department to address this matter. It is the student’s responsibility to contact the Accounts Department, request their invoice and settle their financial obligations prior to the beginning of the semester. If for any reason a student cannot meet their financial obligation, s/he is required to contact the Accounts Department to discuss the implications of failure to make payments on or before the given deadlines and also the possibility of alternative payment plans. The consideration of alternative payment plans is decided on a case by case basis at the discretion of the Accounts Department.STUDENT ACTIVITY FEEThe Student Union Government fee is collected by the University on behalf of the Student Union Government. Each student is required to pay US $50 per semester or US $150 per academic year.STUDENT LIFE ENHANCEMENT FEEThe Student Life Enhancement Fee is a non-academic compulsory ancillary fee that is paid by all students enrolled at All Saints University, College of Medicine, St. Vincent and the Grenadines. This fee is directed towards the development and improvement of all services provided to students. This fee also includes the Internal Examination fees, i.e Exemplify and internal assessments. This does not include NBME Examinations. The Student Life Enhancement Fee for students in the Undergraduate program is US $240 per semester and for students in the Basic Sciences program it is US $300 per semester. The details of the services provided by the Student Life Enhancement Fee can be provided by the Office of Student Affairs and Admissions Department.Tuition Refund PolicyAll refunds due to a student will be processed and issued by the Accounts Department. All refunds will be processed within fourteen business days, after appropriate notice is received from the Office of the Registrar indicating that the student wishes to withdraw from the program. To process approved refunds, students will be required to submit a Refund Request form to the Accounts Department.A refund policy for students in the Undergraduate and Basic Sciences Medical degree program is based on the following criteria:If a student, new or continuing, withdraws prior to the start of the semester, a complete refund of tuition is given.If a registered student withdraws before the end of two weeks after the start of the semester, a refund of 80% tuition will be given.If a registered student withdraws before the end of three weeks after the start of the semester, a refund of 60% will be given.If a registered student withdraws before the end of four weeks after the start of the semester, a refund of 40% will be givenIf a registered student withdraws after the last day of the fourth week from the beginning of the semester, no refund will be given.CLINICAL CLERKSHIP REFUND POLICYFor students who have started their core or elective rotations, no refund can be given if the student wishes to withdraw from a rotation already started. If the student still wishes to withdraw after commencement, s/he will be issued an invoice for the total number of weeks which they were scheduled for prior to starting another rotation. Requests for cancellation of a scheduled rotation must be done one week before the start date of the rotation. There is a $200 fee for last minute (within 24 hours from start of rotation) requests for cancellation of a rotation. In the event of extenuating circumstances, students must immediately contact the Dean of Clinical Affairs if they intend to withdraw during a rotation.LATE REGISTRATION FEESEffective May 2020 semester, students who register after the scheduled registration date will be charged a late registration fee. Students will be responsible for paying the late fee at the time of registration, as per the following:First business day of late registration: US $100Second business day of late registration: US $125Third business day of late registration: US $175Fourth business day of late registration: US $200Any student who arrives for registration after the late registration period has been closed by the Office of the Registrar will be advised to defer their studies until the following semester. The student must report to the Office of Student Affairs and meet with the Dean of Students Affairs to discuss the implications of deferment. Approval for registration after the closure of late registration must be given by the Dean of Student Affairs. The Registration fee after the late registration period has ended is US $300.LATE PAYMENT PENALTYFees are due one months prior to commencement of the semester. If fees are not paid on time and has not made arrangements with the University’s Financial Department, the student will face sanctions, including, but not limited to, de-registration or required deferral to the next semester, not being allowed to attend classes or rotations, etc. A $250 penalty will be applied upon reinstatement. Returning students are required to pay tuition fees one month prior to the beginning of the semester or else a $250 late payment fee will be charged.Any student who is absent for two terms or semesters without providing a valid written request and without obtaining prior approval from the university authorities may be subject to sanction or dismissal from the university; this would appear in the transcript of academic record of such a student.FINANCIAL ARRANGEMENTSIf a student is undergoing financial difficulties, they may reach out to the University’s Financial Department. If the student is granted a financial arrangement by the University and that student subsequently fails to uphold the arrangement terms or conditions and fails to pay related outstanding invoices as and when due, the student will be dismissed from the University.The University may alter the terms of any such arrangement at its discretion and require immediate payment in full of all arrears at any time there is an indication that the student may withdraw or transfer out from the program for any reason without making full payments of all outstanding amounts/arrears. The account may be sent to a collections agency.The University may alter the terms of any such arrangement at its discretion and require immediate payment in full of all arrears at any time there is an indication that the student may be attempting to abscond responsibility for payment of outstanding financial amounts. The account may be sent to a collections agency.TUITION CREDIT OR REFUND FOR SUSPENSION, WITHDRAWAL AND DISMISSALA student who is suspended from the University during the semester in which an incident occurred is eligible for a tuition credit that will be applied to the semester immediately following the period of suspension. The amount of tuition credited is dependent on the refund policy given for voluntary withdrawal from the program. The student will be responsible for all other fees associated with the new semester. A student who is dismissed or who withdraws from the University is eligible for a tuition refund based on the Voluntary Withdrawal policy. If the student has outstanding payments, s/he is obligated to make all payments in full, including full reimbursement of any scholarships awarded by the University. The University will not release any documents or official or unofficial transcripts until the student settles all outstanding payments.

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 GRANTPatient grant costs are broken down into screening, baseline and follow-up visits and medical imaging costs.A. SCREEN FAILURESClinical 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 VISITSDepending 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 TESTSMedical 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 COSTSIf 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 COSTSA. START-UP FEESClinical 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 FEESEC/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 FEESClose-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 FEESGovernment 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 OVERHEADClinical 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 COSTSA. 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 CONSULTINGPhysicians 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 ANALYSISMany 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 COSTOnce 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 COSTSIn 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 MANAGERA 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. SCIENTISTThe 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. BIOSTATISTICIANA 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. QUALITYClinical 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 MANAGEMENTA. PRE-STUDY VISITSPrior 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. MONITORINGOnce 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-OUTOnce 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. MISCELLANEOUSA. INVESTIGATOR MEETINGSInvestigator 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. TRAVELPlan 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 TRANSLATIONSDocument 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 SOLUTIONSClinical 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 FEESRegulatory 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 AMENDMENTSDue 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 EXCHANGEInflation 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 DELAYSEnrolling 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 reimbursementSite costs such as site start-up fees, EC/IRB fees, close-out and storage feesNon-patient costs such as core labatory fees, clinical events committee and data safety monitoring boardLabor costs – clinical research employee salaries or contractor paymentsSite management costs such as pre-study, site initiation, monitoring and close-out visitsMiscellaneous costs such as travel, technology solutions and regulatory filing costsOther factors such as value added tax, inflation, protocol amendment and delays in enrollmentFootnotes[1] Ultimate Guide to Clinical Trial Costs - Clinical Trial Podcast