Patient Access To Investigational Drugs

Patient Access to Investigational Drugs

Introduction • While enrolling subjects into a well controlled clinical study, it is certain that some patients, although they have the disease or condition being studied, will have to excluded from the study in compliance with certain criteria defined in the protocol • Exclusion may be due to number of reasons

Questions… • What happens when patients are excluded from clinical study of investigational drugs & no clinical management technique is known to be effective or no other marketed drug is available to treat the disease or condition?

Questions… • What if the patient has already failed to response to available marketed drugs for the disease or condition? • If an investigational drug exists that may provide necessary relief to the patient by reducing or curing the symptoms of the disease or that may provide hope of increasing the life of the patient, is it unethical to refuse or withhold treatment to the patient?

Expanding Patient Access • Issues – It would be imperative for a physician to recognize the need for treatment with the investigational drug – The physician would have to be willing to accept the responsibility of using an investigational drug & monitoring the patient at closer & more controlled intervals than might be necessary with marketed drugs – To avoid compromising the scientific study of the safety & effectiveness of the investigational drugs through well planned, well controlled clinical studies, the patient must be deemed ineligible for all ongoing clinical studies with the drug

Result • Compassionate use exception, granted upon documented justification, for investigational drugs to be used to treat an individual patient • By identifying an individual patient’s need, contacting a drug company to confirm availability of the drug & submitting a case study & other documents to & receiving approval from FDA & IRB, the physician could treat the patient with the investigational drug

Result • Recognizing that the process was cumbersome and significantly time consuming & realizing that the patient access to promising therapies could be expanded without compromising the development program of the product, the FDA changed the law to provide for the use of investigational drugs in the treatment of an individual patient or small group of patients in a managed way.

3 mech. For treating patients • Single patient use protocol – Can be by the investigator in the form of IND to FDA to treatment between one & five patients – Additional patients may be added to the protocol by filing an amendment to the IND

3 mech. For treating patients • Treatment protocol – Submitted by the study drug sponsor to provide broader access to an investigational product before receiving approval from FDA to market the product – Allows for the treatment of tens to hundreds of patients under the care of any interested physicians who wish to treat patients with the product – Physicians gain participation in the protocol by contacting the study drug sponsor & completing a small number of regulatory documents – The necessary documents are then filed by the study drug sponsor as an amendment to their IND

3 mech. For treating patients • Emergency Use – When no other alternative exists – If the subject has to be provided with the IP drug ( within 30 days), then he may request the investigational drug from the study drug company & may treat the patient with the drug if the full conditions are met • Pt condition is severe or life threatening • No other treatment option exists for the patient • Delay in treatment with the investigational drug could be fatal to the patient • There is no sufficient time to prepare & submit to the FDA the necessary documents for a single patient use protocol • Notification is provided to the FDA by rapid communication, indicating the urgency of the request Cont’d… • IRB is notified & provides approval

• Within 1 week, the investigator must file documentation to the FDA along with all completed regulatory forms.

Regulatory & legal issues • For the expanded use protocol to be justified, sufficient information regarding the efficacy & short term safety of the drug should already have been established. • These protocols are generally limited to the diseases that are life threatening or severely debilitating & to patients who have no alternative therapy

Legal issues • Can a patient sue the FDA or the drug company for access to an investigational or nonmarketed drug • Once given access, can the patient sue the investigator, the drug company or the FDA for damages sustained while taking the drug under expanded use protocols

Legal issues

•YES

Legal issues • The patient has the right to sue or to pursue other available avenues to demand access to a drug that he believes he needs • The patient does not give up any legal rights at any time before, during or after participation in a typical or expanded use clinical study & therefore may seek legal remedy to any damages he alleges

Legal issues • The company may be liable in cases where physicians enter inappropriate patients under an expanded use protocol

Regulatory issues • Drug Availability – Availability may lag far behind demand for the drug & this factor can temper the motivation of the FDA to approve its use. – Lack of supply poses a difficult problem – If a protocol is employed a decision must be made to determine how patients will be selected, because insufficient supply exists for all patients with the disease or condition

Regulatory issues • Paperwork, Monitoring & control Responsibility – Regulatory benefits – Expanded use studies are required to be carried out under the supervision of the sponsor’s IND – This results in monitoring study conduct & verifying, tabulating & reporting the data to the FDA with study drug sponsor – FDA maintains direct responsibility for the emergency use protocols & single patient use protocols submitted by investigators

Package insert • By employing the expanded use protocol, which would include broader patient populations & variations of the indication, the sponsor may gain more liberal labeling from the increased exposure • Side effects & drug interactions observed during the expanded use study are required to be included in the package insert

Advantages & disadvantages for the patient • Expanded use protocol is generally designed to circumvent the strict criteria & to provide select patients with therapeutic advantage not otherwise available to them • Patients enrolling in expanded use studies typically do not qualify for any of the controlled studies with the drug • Often instituted during the late phase I or early phase II before the toxic effects are adequately characterized & certainly before efficacy is demonstrated. • By extending the patient population outside the boundaries defined in the original protocol, the statistical likelihood of side effects increases, as does the potential that a side effect will present itself that can lead to a new indication or formulation of the drug

Advantages & disadvantages for the sponsor • To be cost effective for the sponsor, little or no funding should be expended for patient expense reimbursement or for investigators who desire to prescribe the investigational drug to their patients • Sponsor shld provide clinical trial material, recording instruments, medical & scientific & monitoring expertise to conduct the trials in accordance with the expanded use protocol & current FDA regulations & guidelines.

Advantages & disadvantages for the sponsor • Marketing issues – Expanded use protocol is good selling tool – It allows the physician to become familiar with the drug before its actual marketing – Opportunity for overly enthusiastic drug representatives to try to sell the physician on the drug before FDA approval to market the drug – Charging for the drug under an expanded use program requires prior approval, by the FDA.

Advantages & disadvantages for the sponsor • Ethical & Practical Issues – Difficulties in informed consent • Clinical data not available & patients often desperate for therapy • If the drug demonstrates efficacy in an individual is it ethical & practical to continue that patient on the test drug without the benefit of accurate data? • Limiting participation in the expanded use protocol to those patients who have participated in previous studies with the drug is an additional consideration for the sponsor

Advantages & disadvantages for the sponsor • Ethical & Practical Issues – Clinical Trial Supply • Limited by what the sponsor is able to produce & using the drug in an expanded use protocol places a great strain on the supply available for conducting controlled trials • Companies often question the risk versus benefits of providing high cost, long term drug in an expanded use protocol to patients who ultimately provide little or no helpful study data while potentially excluding patients from the controlled studies

Advantages & disadvantages for the sponsor • Monitoring – Can be especially tenuous under these protocols & the data obtained can often be difficult to interpret

Study Data from the expanded use • Provides an opportunity for obtaining long term data not captured in the shorter & more expensive efficacy & safety data • Side effects can also reveal themselves that could lead to a new indication for the compd or odification of its use. • Safety data management program to be set up

Conclusion • The expanded use protocol when initiated with careful scientific thought & appropriately managed can be an extremely tool for obtaining cost effective information for the FDA, communities & patient • It is the responsibility of the investigator, the sponsor & the FDA to maintain a collaborative environment so that these studies can serve a patient population in need of the drug before its approval & marketing