sumit clinical

Introduction to Clinical Trials: 

Introduction to Clinical Trials Department of Quality Assurance I.S.F. College of Pharmacy( Moga ) Presented by: Sumit kumar mittal M.Pharma (2 nd sem )

Introduction to Clinical Trials – “History and Terminology”: 

Introduction to Clinical Trials – “ History and Terminology”

History: 

History Ethics in Medicine Historically, concerns about the ethics in medicine centered around therapeutics It wasn’t until the middle of the 20 th century (following WWII) that we saw a new emphasis on medical research When they were publicized that national and international efforts to protect the rights and welfare of human subjects in research began Most of these occurrences were situations where investigators ignored the fundamental rights of human subjects

Human Subject: 

Human Subject The Common Rule Definition (45 CFR 46, Section 102) A living individual or collectivety about whom an investigator conducting research obtains information or data through intervention or interaction with the individual or collectivety, or identifiable private information A participant in research either as a recipient of the test article or control. A subject may be a healthy human or a patien

Clinical Trial: 

Clinical Trial Any investigation or study that uses human subjects and is intended to test the clinical effects of an investigational agent and/or to identify any adverse reactions to an investigational agent to assess the safety and efficacy

Protection of Human Subjects in Research Progression: 

Protection of Human Subjects in Research Progression The process will continue to evolve and refine!

The Evolution of the Protection of Human Subjects in Research: 

The Evolution of the Protection of Human Subjects in Research The Food and Drug Act of 1906 The Food, Drug and Cosmetic Act of 1938 The Nuremberg Code - 1947 The 1962 Kefauver-Harris Amendments to the Food, Drug and Cosmetic Act (Thalidomide) The Declaration of Helsinki - 1964 The 1966 Public Health Service IRB and Informed Consent Regulations The Belmont Report -1979 Consolidated DHHS/FDA regulations for human subjects research - 1981

The Evolution of the Protection of Human Subjects in Research (cont.): 

The Evolution of the Protection of Human Subjects in Research (cont.) The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) – 1990 Common Rule - 1991 National Bioethics Advisory Committee – 1995 Data Safety Monitoring Boards (1997, 1999) Office of Protection from Research Risks changes to the Office of Human Research Protections – June, 2000

The Regulatory Environment for Human Subjects Protection: 

The Regulatory Environment for Human Subjects Protection FEDERAL HHS / OHRP Code of Federal Regulations 21 CFR part 50 (FDA) & 45 CFR part 46 (HHS)Financial Administration of Grants and Contracts Billing for clinical trials (Medicare) Health Insurance Portability & Accountability Act of 1996 (HIPAA) STATE Mostly like federal regulations but obligation is to follow whichever is more stringent LOCAL IRBs Office of University Counsel/compliance Financial Conflict of Interest Policies addressing research misconduct and human subjects research non-compliance

The Nuremberg Doctors Trial of 1946: 

The Nuremberg Doctors Trial of 1946 During WWII medical “experiments” were done on concentration camp internees to obtain information useful for the survival of German military personnel under conditions that would be encountered in war. These were mostly survival studies; at high altitudes without oxygen, in frigid water, after wounds of various sorts and severity, after exposures to chemical and biological agents. Many died as a result of these “experiments”.

The Nuremberg Doctors Trial (cont’d): 

The Nuremberg Doctors Trial (cont’d) After a trial of the Nazi leadership by an International Military Tribunal, a trial known as the “Nazi Doctors Trial” was conducted by judges and prosecutors from the U.S. (U.S. vs. Karl Brandt et al.). The 23 defendants, including 20 physicians, were charged with murder, torture and other atrocities. 15 were found guilty and 7 were sentenced to death.

Nuremberg Code - 1947: 

Nuremberg Code - 1947 Informed consent of volunteers must be obtained without coercion in any form Human experiments should be based on prior animal studies Anticipated scientific results should justify the experiment Only qualified scientists should conduct medical research Risk to benefit ratio should be commensurate with the problem

Nuremberg Code (cont’d): 

Nuremberg Code (cont’d) Physical and mental suffering and injury should be avoided There should be no expectation of death or disabling injury from the experiment Investigator should be prepared to stop the experiment if there is indication of danger Subjects should be able to withdraw without penalty

The Declaration of Helsinki - 1964: 

The Declaration of Helsinki - 1964 Written by the World Federation of Physicians and adopted in 1964: Incorporated the Nuremberg Code Defined therapeutic vs. non-therapeutic research Allowed enrollment of certain subjects in therapeutic research without consent so that they might benefit from important medical advances Allowed legal guardians to enroll patients in therapeutic and non-therapeutic research trials

Willowbrook 1963-66: 

Willowbrook 1963-66 This study enrolled institutionalized mentally retarded children in order to investigate the natural history of viral hepatitis with which they were deliberately infected. Willowbrook was overcrowded and only the research wing had room for new patients. Parents had to give permission for their children to be in the study in order for them to be placed at Willowbrook.

Willowbrook (cont’d): 

Willowbrook (cont’d) Coercing parents to enroll their children, using a captive and vulnerable subject population for research, and putting minors at risk for no benefit to them violated all of the ethical principles that should guide physicians doing research.

Tuskegee Study of Untreated Syphilis in Negro Males (1932 – 1972) : 

T uskegee Study of Untreated Syphilis in Negro Males (1932 – 1972) A study to determine the course of untreated syphilis was designed by an agency of the USPHS that later became the CDC Conducted in Tuskegee, Alabama starting in 1932 200-300 black males were to be enrolled The study was to end with a non-therapeutic spinal tap in May 1933

Tuskegee Study of Untreated Syphilis in Negro Males - 2: 

Tuskegee Study of Untreated Syphilis in Negro Males - 2 Went on for the next 10 years without review Penicillin accepted as the treatment for Syphilis in 1943 Subjects were continued in the study untreated and exempted from the WWII draft By 1951 PCN was widely available but subjects were still not treated because it was realized that the study represented a “never again opportunity”

Tuskegee Study of Untreated Syphilis in Negro Males - 3: 

Tuskegee Study of Untreated Syphilis in Negro Males - 3 An expose' was published in the Atlanta Constitution (1972) Senate hearings led to federal regulations (1973) The CDC told survivors that the government would pay their medical bills for the remainder of their lives In 1975 medical coverage was extended to wives and children with congenital syphilis President Clinton publicly apologized to 8 survivors and their families at a white house ceremony in May 1997 National Center for Bioethics in Research established at Tuskegee U. in 1999

General Abbreviations: 

General Abbreviations FDA – Food and Drug Administration IRB – Institutional Review Board IND – Investigational New Drug AE – Adverse Event SAE – Serious Adverse Events ICH – International Conference on Harmonization GCP – Good Clinical Practice CTA – Clinical Trial Agreement

ICH: 

ICH Designed to streamline the process for developing and marketing new drugs internationally Composed of representatives for the pharma industry and the regulatory bodies of the US, Japan, and the European Union Observers include Canada, the European Free Trade Area and WHO

ICH: 

ICH Established several international standards of good clinical practice (GCP) Many countries adopted the guidance as “law” The U.S. (FDA), however, only adopted the ICH as guidance Not regulation Does not have the force of law Compliance is voluntary

Good Clinical Practice (GCP): 

Good Clinical Practice (GCP) “A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate and the rights, integrity, and confidentiality of trial subjects are protected” ICH (1998)

The Belmont Report (1979): 

The Belmont Report (1979) Based on a comprehensive federally-commissioned review which explored the ethical and human rights considerations of human biomedical and behavioral experimentation Resulted in more strenuous protection for human research subjects based on three ethical principles that form the basis for informed consent: Respect for Persons Beneficence Justice

Respect for Persons : 

Respect for Persons Autonomous agents individuals able to make their own informed decisions Persons with diminished capacity are entitled to increased protection. includes children, mentally disabled, prisoners, and pregnant women

Beneficence: 

Beneficence Do no harm. Assess the risk benefit ratio maximize benefits and minimize risks Although there is a need to protect subjects from risk, there is also a need to compare the substantial benefits that may be gained from research

Justice: 

Justice Should not involve persons not likely to benefit from research Requires fairness in selection of subjects Should not systemically draw subjects from certain groups simply because of availability Welfare patients/economically disadvantaged, racial or ethical minorities, institutionalized individuals, very sick patients, or prisoners

“Common Rule”: 

“Common Rule” 45CFR Part 46 Federal regulation that governs the use of human subjects in the US Based on the principles found in the Belmont Report of justice, beneficence, and respect for persons Three main provisions Review and approval of research by an IRB Institutional assurance of compliance Informed consent of subjects

HIPAA: 

HIPAA Mandates secure storage and transmission of heath care information in electronic form Standards for Privacy Standards for Security “PHI” – personal health information Confidentiality De-identifiers

Study: 

Study A scientific study of how a new medicine or treatment works in people Through clinical studies, doctors find new and better ways to prevent, detect, diagnose, control, and treat illnesses a comparison test of a medication or other medical treatment Prospective – going forward Retrospective – looking at what already exists

Sponsor-initiated Study: 

Sponsor-initiated Study Sponsor-initiated Study The protocol is developed solely by the Sponsor and/or Sponsor’s Agent(s) There is no involvement of the PI(s), institution, etc

Investigator-initiated Study: 

Investigator-initiated Study An application where the investigator is conducting the study and acting as the sponsor The investigator both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject An investigator-initiated study does not include a corporation or an agency. The obligations of the investigator include both those of a sponsor and those of an investigator.

Protocol: 

Protocol A document that describes the objective(s), design, methodology, statistical considerations, and organization of a clinical trial Usually gives the background and reason the trial is being conducted, but these could be provided in other documents referenced in the protocol (Investigator’s Brochure) A study plan on which the clinical trial is based Describes, among other things, what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study

Control Group: 

Control Group The standard by which experimental observations are evaluated One group is given the experimental drug or treatment (the experimental group) while the control group is given either standard care and/or a placebo

Investigational New Drug (IND): 

Investigational New Drug (IND) Federal law requires that a drug must have an approved marketing application prior to being transported or distributed across state lines When a sponsor screens a new molecule for pharmacological activity and toxicity in animals and wants to test the drugs diagnostic or therapeutic potential on humans At this point, the molecule changes in legal status Under Federal Food, Drug, and Cosmetic Act, it becomes a new drug subject to regulation

Placebo: 

Placebo When referring to medicines, placebo is a preparation which is pharmacologically inert but which may have a therapeutically effect based solely on the power of suggestion It may be administered in any of the ways in which pharmaceutical products are administered An inactive pill, liquid or powder that has no treatment value The control group will receive the placebo

Informed Consent: 

Informed Consent Form vs process Freely given consent to participate in a clinical research study No coercion Emphasis on “informed” Obtained prior to enrolling the subject

Informed Consent (cont.): 

Informed Consent (cont.) Requirements: Lay language Participant must have sufficient time to consider consenting Reading level Adequate presentation of the facts to the subject and/or representative

Adverse Event (AE): 

Adverse Event (AE) An adverse event is any undesirable experience associated with the use of a medical product in a patient

Serious Adverse Event (SAE): 

Serious Adverse Event (SAE) Death Life-threatening (risk of death) Hospitalization Disability Requires further intervention to prevent additional impairment or disability

Randomization: 

Randomization Random assignment of subjects to either the experimental group or the control group Used to control the imbalance of risk factors within the treatment groups Control of the randomization should rest with a neutral party, if possible Sealed envelopes Randomization center Various ways of randomizing SS # Random number generator

Examples of Randomization – not necessarily good ones,: 

Examples of Randomization – not necessarily good ones, “every fifth person enrolled will go into the control group” SS# - those with odd numbered are control group, even numbers are in the experimental group 100 sealed envelops, within 50 there is a “c”, the other fifty contain a “e”. Envelops are shuffled, distributed to subjects as they enroll

Blinded: 

Blinded Helps to protect against bias Reduces the placebo effect Single Blinded – the subject does not know if (s)he is in the control (placebo) or the experimental group (drug) Double Blinded – both the subject and the PI do not know which group the subject is in Triple Blinded – the subject, the PI and the sponsor do not know to which group the subject is assigned

Blinding Examples: 

Blinding Examples Subject John is enrolled in a trial testing a new drug for cancer. He does not know if he is receiving a placebo or the actual drug. The PI, however, knows that John is receiving the actual drug. Subject Tom is enrolled in a trial testing a new drug for diabetes prevention. He does not know if he is receiving a placebo or the actual drug. The PI also does not know if Tom is receiving the actual drug or the placebo

Pre-clinical Studies: 

Pre-clinical Studies Usually used to test drugs and toxicology on animals Used to evaluate a compound Pre-human testing During this phase, the “IND’ may be submitted to the FDA

Phase I Trials: 

Phase I Trials Used to evaluate and test the pharmacology of the investigational drug and/or the dosing range toxicity Usually uses healthy subjects to determine safety issues N = usually <100 subjects (20 – 80 is optimal)

Phase II Trials: 

Phase II Trials After the safety of the drug has been determined in a Phase I trial Primarily used to collect data on the safety and efficacy of the drug in subjects with the disease the drug is intended to treat Usually, about 100-300 subjects Subjects must fit the inclusion/exclusion criteria

Phase III Trials: 

Phase III Trials Designed to collect data on the side effects, idiosyncrasies, and the effectiveness of the drug Usually >1,000 subjects, multi-centered Usually randomized, blinded and placebo controlled

Phase IV Trials: 

Phase IV Trials Designed to expand the indications for the drug. Takes place after IND is approved and the drug is available Used to re-document the safety of the drug and to gather more information regarding drug interactions To study the drug on additional populations

Contract Research Organization (CRO): 

Contract Research Organization (CRO) An independent contractor with the sponsor Assumes one or more obligations of a sponsor Design of protocol Selection or monitoring of investigations Evaluations of reports Preparation of materials to be submitted to the FDA Are legally liable for the obligations they assume

Site Management Organization (SMO): 

Site Management Organization (SMO) Independent contractor with the clinical investigator Assumes one or more of the regulatory obligations of the clinical investigator Preparation and maintenance of case histories Ensuring compliance with IRB review Informed consent requirements AE reporting Not legally liable for the clinical investigator’s obligations they assume

Contract Concerns (CTA): 

Contract Concerns (CTA) Complex blend of business, law and regulation Requires negotiation and time Publication Intellectual Property Confidentiality Indemnification Subject Injury

Types of IRB Review: 

Types of IRB Review Full review Complete, initial review of the protocol, drug brochure, advertisements, IND, etc Continuing Review Annual required review of the study, progress report, and informed consent form

Types of IRB Review (cont.): 

Types of IRB Review (cont.) Expedited Used for research involving not more than minimal risks to the subjects and in which the only involvement of subjects falls within certain categories Can be utilized for the review of minor revisions that are submitted for a protocol that was previously approved The Chair of the IRB and/or an experienced reviewer can review and approve the research

Types of IRB Review (cont.): 

Types of IRB Review (cont.) Exempt Research Certain types of research, although they involve human subjects, do not require IRB approval Involving normal educational practices Using educational tests Surveys Retrospective collection of data NOTE** Only the IRB has the right to determine if said research is “exempt”

Clinical Trials: 

Clinical Trials Process Compliance Ethical considerations Best practices David Lynch Mayo Clinic dlynch@mayo.edu

Clinical Trials Timeline: 

Clinical Trials Timeline

Clinical Trials Process: 

Clinical Trials Process Pre-award Site selection Confidential disclosure agreement Feasibility assessment Cost proposal development Formal proposal sent to sponsor Negotiation Contract execution

Clinical Trials Process: 

Clinical Trials Process Study initiation Regulatory documents Clinical Trial agreement IRB/IACUC submission and approval Radiation safety, biosafety, environmental health and safety, General Clinical Research Center services (GCRC), etc.

Clinical Trials Process: 

Clinical Trials Process Subject recruitment Recruit and retain human study volunteers Internal vs. external recruitment Funnel concept Monitor progress and adjust efforts Retain

Clinical Trials Process: 

Clinical Trials Process Study coordination/operational considerations Study supplies Informed consent Communications with IRB Clinical trial patient visits Subject remuneration Study documentation Adverse events Etc.

Device Trials: 

Device Trials Verify the device classification Class I Class II Class III Investigational Device Exemption (IDE) Medicare reimbursements

Ongoing Review, Monitoring and Quality Assurance: 

Ongoing Review, Monitoring and Quality Assurance Continuation review Sponsor monitoring Data safety monitoring Quality assurance/improvement

Study Closure and Audit Preparation: 

Study Closure and Audit Preparation Closeout/termination Document retention/destruction

Recent Headlines: 

Recent Headlines Senator targets Schatzberg for conflict of interest Grassley Expands Conflict-of-Interest Probe to University of Texas Tufts doctor is chided on ethics

Issues: 

Issues Timely and complete reporting of trial results Especially when sponsored by drug, device or biological industries These concerns challenge the integrity of academic research and trial sponsors

PowerPoint Presentation: 

Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials Association of American Medical Colleges (AAMC) January 6, 2006 http://www.aamc.org/research/clinicaltrialsreporting/clinicaltrialsreporting.pdf

Principles, Recommendations and Guidelines: 

Principles, Recommendations and Guidelines Based upon sound science Sound ethics Guidance to medical schools, teaching hospitals and professional societies

Who does it affect?: 

Who does it affect? Applies to all clinical trials Conducted in academic medical institutions Regardless of funding source

Ethical Obligations: 

Ethical Obligations Publicize the results Good faith effort to publish, required by contract Peer reviewed jounals Timeliness Link to online repository within 18 months of submission for publication Public sharing of data underlying publications (exception for confidential/proprietary information)

Funding: 

Funding Adequate to cover full costs of analysis and publishing the results

Registration of Clinical Trials: 

Registration of Clinical Trials Fully registered Clinicaltrials.gov and other non-profit, international registries Regularly updated to include links to all published reports

Management of Clinical Trials: 

Management of Clinical Trials For multisite trials, identify a lead or principal investigator Steering committee

Publication and Analysis Committee: 

Publication and Analysis Committee Establish P&A committee, independent of sponsor’s control Right to access data at any time, to ensure integrity, validity and full reporting Sponsor must perform analysis within a defined period of time Sponsor analyses shared with P&A Committee Disseminate results through peer reviewed mechanisms

Individual Publication: 

Individual Publication Potential for bias Typically never part of the original analytic plan, often misleading, strongly discouraged Permitted with conditions After review/comment by P&A committee After publication of study as a whole In absence of full publication, within 2 years from end points or termination

Authorship: 

Authorship Ghost or guest authorship is unacceptable Adoption of ICMJE standards of authorship CONSORT principles guide publication of results Full disclosure of all relevant financial interests of any investigator in all communications Manuscripts should accurately disclose the role of each author Manuscripts should also disclose previous publications involving same protocol or database Manuscripts submitted should be accompanied by pre-specified analysis plan, amendments, deviations, etc.

Introduction to Clinical Trials : 

Introduction to Clinical Trials Budgeting and Post Award Management Susan Cassidy Zipkin, MBA, CRA Brigham and Women’s Hospital szipkin@partners.org

Types of Clinical Trials: 

Types of Clinical Trials PI Initiated Sponsor Initiated Multi Center Clinical NIH Grants/Contracts

Types of Clinical Trials: 

Types of Clinical Trials Fixed Price Per Patient Can the investigator Recruit the # of patients? Does the budget support the work? If the answer to either is no, JUST SAY NO!

Types of Clinical Trials: 

Types of Clinical Trials You need to know if it is a winner or a loser There will be some cases when a department will want to take on a trial, even knowing it will not make/ or even may result in a deficit. You should make sure you have this understanding in writing with a plan on how the deficit will be resolved.

Types of Clinical Trials: 

Types of Clinical Trials Make sure the agreement is reviewed/negotiated by the experienced staff in your Corporate Sponsored Research Office if this service is available to you. The company will always tell you your price is the highest The PI will always want to go with with a lower price to please the company

Medicare Cost Analysis (MCA): 

Medicare Cost Analysis (MCA) Many Institutions require that an MCA is performed prior to negotiating a clinical trial This is required to insure that no procedures are double billed - i.e. billed to Medicare and included in the trial budget. Also insures that any procedures that would NOT be covered by Medicare are not left out of the trial billing grid. This eliminates the possibility that study expenses fall through the cracks and are never recovered by sponsor or Medicare.

MCA & Budget Development: 

MCA & Budget Development Study procedures vs. standard of care Someone skilled to do so should review the entire protocol and determine hours of time, and procedures to be charged to the study Risks associated with mis-charging care ie. FRAUD

Important Items to Consider When Developing Your Budget: 

Important Items to Consider When Developing Your Budget Failure rate/drop out % Storage charges for 7 years Paying % effort or fee for service Internal or outsource services or procedures Research Discounts NIH vs. Corporate

Important Items to Consider When Developing Your Budget: 

Important Items to Consider When Developing Your Budget Subject compensation Parking reimbursements for subjects Meal reimbursements for subjects

Important Items to Consider When Developing Your Budget: 

Important Items to Consider When Developing Your Budget Clinical activities you may see in protocol Lab fees Recovery rooms Anesthesia Radiology Pharmacy Nursing

Important Items to Consider When Developing Your Budget: 

Important Items to Consider When Developing Your Budget Professional fees for interpretation of clinical services Include an escalation rate for technical and professional

Important Items to Consider When Developing Your Budget: 

Important Items to Consider When Developing Your Budget What type of clinical trials can affect your budget Study site for a multi site trial Coordinating center for a multi site trial

Important Items to Consider When Developing Your Budget: 

Important Items to Consider When Developing Your Budget Additional responsibilities and costs are associated with being the coordinating center Including but not limited to additional administrative expense overnight shipping storage supplies

Budget Development – Salary Expense: 

Budget Development – Salary Expense PI Effort how to allocate You must make sure that an appropriate amount of effort is allocated in the budget – don’t give away the PI’s time. This is a real cost. Other Salaries to budget for: Clinical specialists Research coordinator Technicians Nurses Administrative/Clerical

Upfront Costs: 

Upfront Costs

Examples of Upfront Costs: 

Examples of Upfront Costs The most common is the IRB fee Recruitment expenses - these costs must be reimbursed in a timely manner so as not to force the account into deficit Advertising often written in as “reimbursable expenses” – this can be requested up front. Administrative time for the PI and staff to prepare items for example when FDA approval is being pursued.

Upfront Costs: 

Upfront Costs Build in clause to pay a certain amount in the event of study failure Ie ½ year salary of study coordinator.

Budget Development: 

Budget Development Who will bill the sponsor? It is important to establish this prior to the start of the trial so that there is no misunderstanding and bills are processed on a timely basis. How Much will be paid upfront? What are the milestones that must be reached in order to trigger payment from sponsor? How will the information flow? Will Dept bill sponsor? Or will payment come automatically as milestones are reached?

Budget Development- Payment Terms: 

Budget Development- Payment Terms Make sure you negotiate favorable Payment terms in order to keep your account out of deficit. For a trial with 10 patients at $2,500/per patient

Budget Development- Payment Terms: 

Budget Development- Payment Terms Payment MILESTONE AMOUNT 1 Initial Payment upon shipment of drug $2,500 2 After 3 subjects completed $7,500 3 After 2 subjects completed $5,000 4 After 2 patients completed $5,000 5 Final payment after all case report forms are completed and close out visit is complete $5,000 What a sponsor may propose:

Budget Development-Payment Terms: 

Budget Development-Payment Terms Payment MILESTONE AMOUNT 1 Initial Payment+ IRB FEE upon execution of contract $6,500 2 After 3 subjects randomized $7,500 3 After 2 subjects completed $5,000 4 After 2 patients completed $5,000 5 Final payment after all case report forms are completed and close out visit is complete $2,500 What YOU want to PROPOSE:

Budget Development: 

Budget Development Determine if there is a departmental policy for residual/deficit spending Know the expectations ahead of time

Managing The Trial: 

Managing The Trial

Managing The Trial: 

Managing The Trial Once the contract has been fully executed the Office of Sponsored Programs will set up an account You need to be sure that there is an internal mechanism to charge patient charges to the account BEFORE patients are seen. Insure any upfront charges are allocated to the new account number.

Managing The Trial: 

Managing The Trial Arrange a meeting with the key players: The PI, study coordinator, and departmental administrator. Discuss recruitment, scheduling, effort allocation of personnel, information flow, and billing.

Managing The Trial: 

Managing The Trial Communication with the study coordinator is crucial to successful management of the trial Set up a standard schedule to receive information - When patients are seen or on a weekly/monthly basis. What procedures were performed and which study should they have been charged to?

Managing The Trial: 

Managing The Trial The departmental administrator, study coordinator and the PI must verify that correct expenses and income hit the account Monthly review of actual charges on ledger Make any adjustments necessary on a timely basis Track income, follow up on unpaid invoices in a timely basis

Managing The Trial: 

Managing The Trial When is the right time to apply the PI and other study staff’s effort ? Things to consider Where is this effort being charged while they are seeing patients on the trial? For PI- is this clinical time that can be retroactively charged back to the trial? DANGER Avoid parking effort on another sponsored project

Managing The Trial: 

Managing The Trial Most clinical trials income comes in on a per patient basis. Budget is only a projection. Options for representing budget on reports: “1 patient income”, or “0” ton insure PI does not overspend to “budgeted amount”

Other Support: 

Other Support Do Clinical Trials have to be reported on other support documents? Lump together all trials? Larger trials should be listed individually

Closing Out The Trial: 

Closing Out The Trial

Closing out the Trial: 

Closing out the Trial How do you handle a residual balance? Were all appropriate charges charged to the account? Were all budgeted personnel expenses charged? Did the appropriate $ amount for the number of patients seen hit the account? Has all the income been received? Is the residual reasonable/justifiable?

Closing out the Trial: 

Closing out the Trial Your institution may require the PI to certify to all of the above and to be responsible for any charges that are identified as belonging to the study that arise at a later date Once these requirements have been met/certified, the residual balance can be transferred to a discretionary account.

Closing out the Trial: 

Closing out the Trial Who will cover the deficit on trials should it occur? You should have a plan for how this will be covered before the trial begins

Questions?: 

Questions?