sexta-feira, fevereiro 03, 2006
Acerca de terapêuticas de resgate e acesso alargado
Research Principles for Clinical Studies Using Volunteers with Resistance to All Commercially Available HIV Medications
After getting important feed back from several key activists and assessing the main issues facing patients trying to access multiple active agents for their survival, SalvageTherapies.org has produced the following position statement to guide the pharmaceutical industry in designing ethical and humane research protocols of new agents for the treatment of HIV disease:
1- Patients with resistance to all commercially available HIV medications should not be exposed to monotherapy of any kind, or to “virtual monotherapy”, where one new agent is added to a failing regimen.
2- We recognize that pharmacokinetic (PK) clinical trials including the study of agents administered individually and as a component of a multiple-drug regimen, are extremely important. Whenever possible, PK evaluations should be conducted in HIV-negative study volunteers. When the participation of patients with resistance to all available HIV medications is required, exposure to the experimental agents should be limited to a time period that will not lead to resistance to the study drug. If such period is not known, patients should be clearly informed about the potential risks for resistance in the respective study consent forms.
3- We strongly encourage collaboration among the various pharmaceutical companies with anti-retroviral agents in development to perform early interaction studies so that lack of interaction data does not represent a barrier to performing phase III combination studies, OLSS and expanded access programs (EAP) that allow the use of more than one investigational agent. The U.S. Food and Drug Administration (FDA) has also expressed support for this initiative, as it represents the greater hope for heavily treatment-experienced patients.
4- No unnecessary exclusion criteria should be placed on studies unless there is a strong indication of considerable risks to the well-being of the target population. Examples include exclusions of patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection, patients with CD4+ cells counts below 50 cells/mm³, and exclusion of Fuzeon (T-20) or other agents in the same phase of development due to lack of interaction data.
5- We recognize that an extensive clinical research program is necessary to determine the clinical utility of an experimental agent, including its various risks and benefits. Here is an overview of the minimum requirements to be satisfied in order to advocate for the approval and use of an experimental agent:
a. PK interaction studies prior to the implementation and enrollment of phase III studies that include all approved and experimental agents in the late stages of development which are most likely to be used in combination with the study drug, opportunistic infection prophylaxis, methadone, and contraceptive hormones. Other interaction data including psychotropic agents, lipid-lowering agents, anti-hypertensive treatments, antacids and agents used for gastric reflux, antiseizure medications, and erectile dysfunction treatments should be obtained prior to FDA approval;
b. Enrollment of people of color, women and other under represented populations should be given high priority, including in pivotal PK studies and phase II/III clinical efficacy studies. Several PK studies have indicated possible sex and gender based differences in drug metabolism that may affect dosing decisions.
c. When considering studies of combination experimental agents, emphasis should be placed on regimens employing two distinct characteristics: regimens that are most likely to be successful, and regimens that are most likely to be used in the “real world.”
6- Community representation in Data Safety Review Boards (DSMB) is strongly recommended for all phase II and phase III studies.
7- Proactive expanded access program (EAP) discussions should begin early with community consultation. The following important considerations should be taken into account:
a. EAPs should be implemented as soon as dosing, safety, efficacy and interaction data from phase II A/B studies are available. Smaller Open Label Safety Studies (OLSS) can be started before EAPs to give patients in dire need of a new agent prompt access in a protocol setting without having to enroll in parallel phase III studies that may present the risk of sequential monotherapy in a placebo + optimized background therapy (OBT) arm.
b. OLSS and EAPs should always facilitate access to more than one active agent and to other experimental agents that have been studied in previous interaction studies that are in or near Phase III development or available through other EAPs.
c. The use of approved agents should not be excluded unless a safety or interaction issue is clearly present.
d. Companies should plan in advance to minimize any drug supply limitations that would prevent early access for people with the greatest clinical need who cannot construct a viable regimen. When drug supply limitations are an unavoidable issue, we recommend a staged process that offers access to those with less than or equal to 100 CD4 cell count and that works up to higher or no CD4 cell count limitation when supply permits. This staged EAP should be preformed with community consultation and regular intervals of status notification to the community, including number of patients screened, enrolled, and on waiting lists.
e. Whenever possible, EAPs should be made available to those patients who have screened out of phase III studies and/or those with geographical limitations that prevent their participation in studies.
f. EAPs should not be site specific and should include community clinics that treat uninsured patients. No geographic limitations should be present for patient access.
g. Companies should optimize the EAP paper work process to enable physicians with busy practices to use the program without road blocks. Practical ways to reimburse for nurses’ time should be sought. It is suggested that a national institutional review board (IRB) should be used to minimize local IRB delays and complications.
For more information, email nelsonvergel@yahoo.com and visit www.salvagetherapies.org
After getting important feed back from several key activists and assessing the main issues facing patients trying to access multiple active agents for their survival, SalvageTherapies.org has produced the following position statement to guide the pharmaceutical industry in designing ethical and humane research protocols of new agents for the treatment of HIV disease:
1- Patients with resistance to all commercially available HIV medications should not be exposed to monotherapy of any kind, or to “virtual monotherapy”, where one new agent is added to a failing regimen.
2- We recognize that pharmacokinetic (PK) clinical trials including the study of agents administered individually and as a component of a multiple-drug regimen, are extremely important. Whenever possible, PK evaluations should be conducted in HIV-negative study volunteers. When the participation of patients with resistance to all available HIV medications is required, exposure to the experimental agents should be limited to a time period that will not lead to resistance to the study drug. If such period is not known, patients should be clearly informed about the potential risks for resistance in the respective study consent forms.
3- We strongly encourage collaboration among the various pharmaceutical companies with anti-retroviral agents in development to perform early interaction studies so that lack of interaction data does not represent a barrier to performing phase III combination studies, OLSS and expanded access programs (EAP) that allow the use of more than one investigational agent. The U.S. Food and Drug Administration (FDA) has also expressed support for this initiative, as it represents the greater hope for heavily treatment-experienced patients.
4- No unnecessary exclusion criteria should be placed on studies unless there is a strong indication of considerable risks to the well-being of the target population. Examples include exclusions of patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection, patients with CD4+ cells counts below 50 cells/mm³, and exclusion of Fuzeon (T-20) or other agents in the same phase of development due to lack of interaction data.
5- We recognize that an extensive clinical research program is necessary to determine the clinical utility of an experimental agent, including its various risks and benefits. Here is an overview of the minimum requirements to be satisfied in order to advocate for the approval and use of an experimental agent:
a. PK interaction studies prior to the implementation and enrollment of phase III studies that include all approved and experimental agents in the late stages of development which are most likely to be used in combination with the study drug, opportunistic infection prophylaxis, methadone, and contraceptive hormones. Other interaction data including psychotropic agents, lipid-lowering agents, anti-hypertensive treatments, antacids and agents used for gastric reflux, antiseizure medications, and erectile dysfunction treatments should be obtained prior to FDA approval;
b. Enrollment of people of color, women and other under represented populations should be given high priority, including in pivotal PK studies and phase II/III clinical efficacy studies. Several PK studies have indicated possible sex and gender based differences in drug metabolism that may affect dosing decisions.
c. When considering studies of combination experimental agents, emphasis should be placed on regimens employing two distinct characteristics: regimens that are most likely to be successful, and regimens that are most likely to be used in the “real world.”
6- Community representation in Data Safety Review Boards (DSMB) is strongly recommended for all phase II and phase III studies.
7- Proactive expanded access program (EAP) discussions should begin early with community consultation. The following important considerations should be taken into account:
a. EAPs should be implemented as soon as dosing, safety, efficacy and interaction data from phase II A/B studies are available. Smaller Open Label Safety Studies (OLSS) can be started before EAPs to give patients in dire need of a new agent prompt access in a protocol setting without having to enroll in parallel phase III studies that may present the risk of sequential monotherapy in a placebo + optimized background therapy (OBT) arm.
b. OLSS and EAPs should always facilitate access to more than one active agent and to other experimental agents that have been studied in previous interaction studies that are in or near Phase III development or available through other EAPs.
c. The use of approved agents should not be excluded unless a safety or interaction issue is clearly present.
d. Companies should plan in advance to minimize any drug supply limitations that would prevent early access for people with the greatest clinical need who cannot construct a viable regimen. When drug supply limitations are an unavoidable issue, we recommend a staged process that offers access to those with less than or equal to 100 CD4 cell count and that works up to higher or no CD4 cell count limitation when supply permits. This staged EAP should be preformed with community consultation and regular intervals of status notification to the community, including number of patients screened, enrolled, and on waiting lists.
e. Whenever possible, EAPs should be made available to those patients who have screened out of phase III studies and/or those with geographical limitations that prevent their participation in studies.
f. EAPs should not be site specific and should include community clinics that treat uninsured patients. No geographic limitations should be present for patient access.
g. Companies should optimize the EAP paper work process to enable physicians with busy practices to use the program without road blocks. Practical ways to reimburse for nurses’ time should be sought. It is suggested that a national institutional review board (IRB) should be used to minimize local IRB delays and complications.
For more information, email nelsonvergel@yahoo.com and visit www.salvagetherapies.org
