atm Therapeutic targeting of p300/CBP HAT domain for the treatment of NUT midline carcinoma By feeds.nature.com Published On :: 2020-05-04 Full Article
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atm Clinical and radiographic evaluation of indirect pulp treatment of young permanent molars using photo-activated oral disinfection versus calcium hydroxide: a randomized controlled pilot trial By www.nature.com Published On :: 2020-03-17 Full Article
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atm Lebanon has formed a controversial new government in a polarised, charged atmosphere, and protesters are not going to be easily pacified by its promises, explains Rami Khoury. By feedproxy.google.com Published On :: Jan 22, 2020 Jan 22, 2020The fourth consecutive month of Lebanon's unprecedented political and economic crisis kicked off this week with three dramatic developments that will interplay in the coming months to define the country's direction for years to come: Escalating protests on the streets, heightened security measures by an increasingly militarising state, and now, a new cabinet of controversial so-called "independent technocrats" led by Prime Minister-designate Hassan Diab. Seeking to increase pressure on the political elite to act responsibly amid inaction vis-a-vis the slow collapse of the economy, the protesters had launched the fourth month of their protest movement, which had begun on 17 October last year, with a 'Week of Anger', stepping up their tactics and targeting banks and government institutions. Full Article
atm Lebanon has formed a controversial new government in a polarised, charged atmosphere, and protesters are not going to be easily pacified by its promises, explains Rami Khoury. By feedproxy.google.com Published On :: Jan 22, 2020 Jan 22, 2020The fourth consecutive month of Lebanon's unprecedented political and economic crisis kicked off this week with three dramatic developments that will interplay in the coming months to define the country's direction for years to come: Escalating protests on the streets, heightened security measures by an increasingly militarising state, and now, a new cabinet of controversial so-called "independent technocrats" led by Prime Minister-designate Hassan Diab. Seeking to increase pressure on the political elite to act responsibly amid inaction vis-a-vis the slow collapse of the economy, the protesters had launched the fourth month of their protest movement, which had begun on 17 October last year, with a 'Week of Anger', stepping up their tactics and targeting banks and government institutions. Full Article
atm Lebanon has formed a controversial new government in a polarised, charged atmosphere, and protesters are not going to be easily pacified by its promises, explains Rami Khoury. By feedproxy.google.com Published On :: Jan 22, 2020 Jan 22, 2020The fourth consecutive month of Lebanon's unprecedented political and economic crisis kicked off this week with three dramatic developments that will interplay in the coming months to define the country's direction for years to come: Escalating protests on the streets, heightened security measures by an increasingly militarising state, and now, a new cabinet of controversial so-called "independent technocrats" led by Prime Minister-designate Hassan Diab. Seeking to increase pressure on the political elite to act responsibly amid inaction vis-a-vis the slow collapse of the economy, the protesters had launched the fourth month of their protest movement, which had begun on 17 October last year, with a 'Week of Anger', stepping up their tactics and targeting banks and government institutions. Full Article
atm Lebanon has formed a controversial new government in a polarised, charged atmosphere, and protesters are not going to be easily pacified by its promises, explains Rami Khoury. By feedproxy.google.com Published On :: Jan 22, 2020 Jan 22, 2020The fourth consecutive month of Lebanon's unprecedented political and economic crisis kicked off this week with three dramatic developments that will interplay in the coming months to define the country's direction for years to come: Escalating protests on the streets, heightened security measures by an increasingly militarising state, and now, a new cabinet of controversial so-called "independent technocrats" led by Prime Minister-designate Hassan Diab. Seeking to increase pressure on the political elite to act responsibly amid inaction vis-a-vis the slow collapse of the economy, the protesters had launched the fourth month of their protest movement, which had begun on 17 October last year, with a 'Week of Anger', stepping up their tactics and targeting banks and government institutions. Full Article
atm Lebanon has formed a controversial new government in a polarised, charged atmosphere, and protesters are not going to be easily pacified by its promises, explains Rami Khoury. By feedproxy.google.com Published On :: Jan 22, 2020 Jan 22, 2020The fourth consecutive month of Lebanon's unprecedented political and economic crisis kicked off this week with three dramatic developments that will interplay in the coming months to define the country's direction for years to come: Escalating protests on the streets, heightened security measures by an increasingly militarising state, and now, a new cabinet of controversial so-called "independent technocrats" led by Prime Minister-designate Hassan Diab. Seeking to increase pressure on the political elite to act responsibly amid inaction vis-a-vis the slow collapse of the economy, the protesters had launched the fourth month of their protest movement, which had begun on 17 October last year, with a 'Week of Anger', stepping up their tactics and targeting banks and government institutions. Full Article
atm Lebanon has formed a controversial new government in a polarised, charged atmosphere, and protesters are not going to be easily pacified by its promises, explains Rami Khoury. By feedproxy.google.com Published On :: Jan 22, 2020 Jan 22, 2020The fourth consecutive month of Lebanon's unprecedented political and economic crisis kicked off this week with three dramatic developments that will interplay in the coming months to define the country's direction for years to come: Escalating protests on the streets, heightened security measures by an increasingly militarising state, and now, a new cabinet of controversial so-called "independent technocrats" led by Prime Minister-designate Hassan Diab. Seeking to increase pressure on the political elite to act responsibly amid inaction vis-a-vis the slow collapse of the economy, the protesters had launched the fourth month of their protest movement, which had begun on 17 October last year, with a 'Week of Anger', stepping up their tactics and targeting banks and government institutions. Full Article
atm Lebanon has formed a controversial new government in a polarised, charged atmosphere, and protesters are not going to be easily pacified by its promises, explains Rami Khoury. By feedproxy.google.com Published On :: Jan 22, 2020 Jan 22, 2020The fourth consecutive month of Lebanon's unprecedented political and economic crisis kicked off this week with three dramatic developments that will interplay in the coming months to define the country's direction for years to come: Escalating protests on the streets, heightened security measures by an increasingly militarising state, and now, a new cabinet of controversial so-called "independent technocrats" led by Prime Minister-designate Hassan Diab. Seeking to increase pressure on the political elite to act responsibly amid inaction vis-a-vis the slow collapse of the economy, the protesters had launched the fourth month of their protest movement, which had begun on 17 October last year, with a 'Week of Anger', stepping up their tactics and targeting banks and government institutions. Full Article
atm Lebanon has formed a controversial new government in a polarised, charged atmosphere, and protesters are not going to be easily pacified by its promises, explains Rami Khoury. By feedproxy.google.com Published On :: Jan 22, 2020 Jan 22, 2020The fourth consecutive month of Lebanon's unprecedented political and economic crisis kicked off this week with three dramatic developments that will interplay in the coming months to define the country's direction for years to come: Escalating protests on the streets, heightened security measures by an increasingly militarising state, and now, a new cabinet of controversial so-called "independent technocrats" led by Prime Minister-designate Hassan Diab. Seeking to increase pressure on the political elite to act responsibly amid inaction vis-a-vis the slow collapse of the economy, the protesters had launched the fourth month of their protest movement, which had begun on 17 October last year, with a 'Week of Anger', stepping up their tactics and targeting banks and government institutions. Full Article
atm Lebanon has formed a controversial new government in a polarised, charged atmosphere, and protesters are not going to be easily pacified by its promises, explains Rami Khoury. By feedproxy.google.com Published On :: Jan 22, 2020 Jan 22, 2020The fourth consecutive month of Lebanon's unprecedented political and economic crisis kicked off this week with three dramatic developments that will interplay in the coming months to define the country's direction for years to come: Escalating protests on the streets, heightened security measures by an increasingly militarising state, and now, a new cabinet of controversial so-called "independent technocrats" led by Prime Minister-designate Hassan Diab. Seeking to increase pressure on the political elite to act responsibly amid inaction vis-a-vis the slow collapse of the economy, the protesters had launched the fourth month of their protest movement, which had begun on 17 October last year, with a 'Week of Anger', stepping up their tactics and targeting banks and government institutions. Full Article
atm Health Policy Issue Brief: Four A's of Expanding Access to Life-Saving Treatments and Regulatory Implications By webfeeds.brookings.edu Published On :: Thu, 31 Jul 2014 15:27:00 -0400 Please note that this Engelberg Center for Health Care Reform Health Policy Issue Brief first appeared in the Health Affairs Blog on July 31, 2014. Click here for the Health Affairs Blog version. Abstract Individual patient expanded access is a process by which patients can obtain investigational drugs that have not been approved by the Food and Drug Administration (FDA) outside of a clinical trial setting from biopharmaceutical companies when no other alternative therapy is available. Currently, no industry-wide structural principles exist to help companies navigate this process while balancing the needs of getting a drug to the market as quickly as possible with providing potentially life-saving treatment to individual patients. The Engelberg Center convened a stakeholder group to identify common themes and identify common principles related to expanded access, as none currently exist. The result was 4 A’s - Anticipation, Accessibility, Accountability, and Analysis – to help assist patients, providers, and companies with expanded access. Process and capacity building recommendations for the FDA also were proposed to assist companies with sustaining expanded access programs. Call to Action: The Importance of Expanded Access Programs Individual patient expanded access, sometimes termed “compassionate use,” refers to situations where access to a drug still in the development process is granted to patients on a case-by-case basis outside of a clinical trial, prior to completion of mandated clinical trials and approval by the Food and Drug Administration (FDA). This typically involves filing a single patient or emergency investigational new drug (IND) request with the Food and Drug Administration and voluntary release of the drug by the manufacturer. Generally, the following criteria must be met: there is reasonable expectation of meaningful benefit despite the absence of definitive clinical trial data, the patient has a serious or life-threatening condition, there are no comparable or satisfactory treatment alternatives, and there are no suitable clinical trials for the drug available to the patient. This form of expanded access, which is the focus of this paper, is different from the situation in which a drug is discharged to a large group of needy patients in the interval between successful phase 3 trials and presumed FDA approval, a strategy often termed a “treatment” IND or protocol, which was initially used in the 1980s for releasing zidovudine to patients with acquired immune deficiency syndrome. The Engelberg Center for Health Care Reform at the Brookings Institution recently invited senior leaders from several pharmaceutical companies, two bioethicists, a senior FDA representative, and a patient advocate to share experiences and discuss organizational strategies related to expanded access (see acknowledgements). A driving factor for this meeting was a recent flurry of highly public cases of desperate patients seeking access to experimental drugs, which lead to social media campaigns and media coverage. Such cases included 7-year-old Josh Hardy (brincidofovir from Chimerix for disseminated adenovirus infection), 45-year-old Andrea Sloan (BMN673 from BioMarin for ovarian cancer), 41-year-old Nick Auden (pembrolizumab from Merck for melanoma), and 6-year-old Jack Fowler (intrathecal idursulfase from Shire for Hunter Syndrome). Expanded access requests to the FDA for new patients are increasing, from 1,000 patients nationwide in 2010 to more than 1,200 in 2012.[i] (This is likely an underestimate, since it does not include appeals made directly to companies.) In the wake of these events, it became clear that many biopharmaceutical companies had varying experiences and policies related to such access. From the domestic regulatory standpoint, the FDA revised its expanded access regulations in 2009, which define criteria that must be met to authorize expanded access, list requirements for expanded access submissions, describe safeguards that will protect patients, and preserve the ability to develop meaningful data about the use of the drug. Biopharmaceutical companies typically face a complex global environment in which legal and regulatory frameworks can differ substantially. At the meeting, a senior FDA representative indicated the agency has approved over 99 percent of expanded access requests submitted via single patient or emergency INDs since 2009, suggesting the regulatory agency is not a major barrier to expanded access. As such, provided the access request is reasonably related to the potential benefits of the drug, the biopharmaceutical company is almost solely responsible for the decision and liability regarding whether to grant expanded access to an individual. Still, the public belief persists that the FDA is the main bottleneck that restricts access. In April 2014, Representative Morgan Griffith (R-VA) proposed H.R. 4475, The Compassionate Freedom of Choice Act of 2014, designed to restrict the FDA’s ability to prevent the use of investigational drugs in terminally ill patients. Similarly, some states have passed “Right to Try” legislation to reduce FDA oversight, but contains no requirement that companies must make drugs available.[ii] The goal of our meeting was to identify common themes and possibly broad outlines to suggest industry-wide policies related to expanded access, as none currently exist. The group first discussed background issues related to expanded access and agreed on definitions. The meeting then focused on three topics. First, the group participants who play key roles in evaluating expanded access requests were invited to share narrative experiences in specific clinical cases, in an effort to lay the groundwork for trust and open discussion. Second, the group was asked to identify internal industry-specific structural barriers, such as the existence of clear procedures or tracking mechanisms within companies to handle requests. Finally, the participants reflected on situations in which expanded access may not be appropriate, or where regulatory barriers or liability concerns may hinder expanded access. This paper reflects the authors’ observations and assessment of the internal and external landscape, based upon information provided by the meeting participants. Laying the Groundwork with Shared Experiences The FDA allows companies to provide drugs and charge individual patients that do not meet the enrollment criteria for clinical trials geared towards regulatory approval through expanded access programs.[iii] These programs are meant to provide the drug directly to treat the patient’s condition, rather than having the primary goal of collecting efficacy or detailed safety data in support of approval. Before 1987, the FDA lacked formal recognition of expanded access, although investigational drugs were provided informally.[iv] Since then, the FDA has instituted novel classes of individual INDs so that a company sponsor or licensed physician can legally obtain treatment access from the FDA to provide a drug while it is still in the approval process.[v] Essentially, this provides companies a legal exception from the law to ship unapproved drugs across state lines, and if they desire, to charge for them. These INDs are designed solely for the potential benefit of desperate patients and not intended to formally collect safety or efficacy data that could potentially inform a regulatory decision, but can have regulatory impact, nonetheless. At the outset, several participants objected to the term “compassionate use,” since it introduces inherent value decisions, can emotionally charge discussions, and does not recognize that there may be valid and ethically appropriate reasons for denial. The generally agreed upon term “expanded access,” is used throughout this paper. (One participant suggested the term “early access.”) Ideally, the term would make it obvious that this is access to an unapproved drug, in order to temper expectations of favorable results. Somewhat confusingly, the FDA uses the terms “expanded access,” “access,” and “treatment use” interchangeably to refer to the use of a drug, and of which none clearly identify the stage of development.[vi] Participants shared numerous examples of requests for expanded access and explained that their companies handle anywhere from a handful to several hundred requests per year. The following selected stories illustrate the wide range of experiences and situations that companies encounter when navigating the complex decisions involved in administering an expanded access program. Several other examples were discussed and the specific participants expressed that they would be willing to share these particular examples publicly. Chimerix, a 54-employee company based in Durham, North Carolina, is developing the drug brincidofovir and previously had created an intermediate expanded access protocol for the drug (CMX001-350) as encouraged by the FDA following over 200 emergency INDs granted for access to brincidofovir.[vii] One such case was for an armed services member with previously undiagnosed acute myelogenous leukemia who developed life-threatening vaccinia infection following smallpox vaccination in 2009.[viii] The patient received the drug from Chimerix through an emergency IND. After two years, the company had not secured FDA approval for the drug and eliminated expanded access in February 2012 in order to focus on studies which would inform a regulatory decision. In March 2014, Chimerix originally rejected an emergency IND request for 7-year old, Josh Hardy, who was critically ill from disseminated adenovirus infection after bone marrow transplantation. A highly public social media campaign targeted the company in the wake of this decision, and the experience was traumatizing for many of the employees. Following discussion with the FDA, Chimerix initiated a new clinical trial for the treatment of adenovirus infection in order to collect safety and efficacy data to support an NDA submission. Hardy was the first patient enrolled in the clinical trial, and his family reported through several media outlets that he recovered from the adenovirus infection and was discharged home. One biopharmaceutical company representative described receiving a middle-of-the-night telephone call directly at home, with an emergent, time-sensitive request for an experimental therapy for a critically ill child with a rare acute disease in a foreign pediatric intensive care unit, where regulatory standards were different from those in the U.S. The ideal pediatric dosage was unknown, and only limited safety data and clinical details were available. Urgent efforts were made to gather more information and the request was approved, but despite these efforts the patient did not survive. Bristol-Myers Squibb began a clinical trial for a cancer drug several years ago.[ix] A woman with pancreatic cancer enrolled in the trial and saw that her tumor was no longer growing. After the 3.5 year trial, the study closed because the drug was deemed ineffective for all other patients and was not approved for further development. However, the company continued to provide the drug for the one woman for whom the drug was effective through a single patient IND for an additional 9 years. To demonstrate the volume of expanded access requests, one participant showed several messages on his mobile device during the half-day discussion, directly from patients who had located his email addresses through on-line searches, to plead for expanded access to an anticancer therapy. Development of Structural Principles: The Four A's Broadly, no specific industry-wide consensus on expanded access procedures exists. As a result, there is significant variation in company policies and procedures. During this phase of discussion, participants shared their own company strategies and suggested possible areas of consensus that might form the basis for shared principles and industry-wide practices. These suggestions fell into four categories, which we termed the 4 “A’s”: Anticipation, Accessibility, Accountability, and Analysis (see Figure 1). First, the group agreed that large and small companies should anticipate the need for and creation of expanded access programs when developing drugs expected to generate expanded access requests and as part of the drug development plan. This is particularly important for drugs that might be considered for priority or breakthrough designation during FDA approval. In these cases, companies should strongly consider developing a written expanded use policy with clear guidelines for inclusion and exclusion, which would also feature a defined review process, clear decision making criteria, and a defined time frame for response to requests. This also allows companies to plan for the demands that may be placed on their supply chain and staff resources to ensure sufficient supply for investigational and expanded use purposes. Identifying a decision maker within each company and for each disease area/product will also help patients or physicians reach the appropriate contact when requesting a drug, as well as assist the company in gaining expertise in responding to these requests. For example, one large company identifies one point of contact for all expanded access requests regarding each product and posts that individual’s contact information on the website. In the early stages of drug development, supplies of investigational drugs are extremely limited. This is often because the technically-challenging process of optimizing drug product manufacture takes a considerable amount of time. Low yielding manufacture batches are not uncommon at the early phases of research. Some companies do not approve expanded access requests because they do not have enough of the drug in stock to supply these external requests and meet the needs of investigational study patients and individuals participating in clinical trials, an issue which may be particularly acute for biologics. Smaller companies may have more resource constraints, such as inadequate staff to manage requests or supply chain and logistics issues. One representative suggested that if a company had early transparency from regulators about the final numbers of subjects they would be willing to accept to achieve drug development milestones, it would make it much easier for the company to feel less reservation about its drug supply. (It may be beneficial for companies to analyze their financial ability to provide drugs potentially at no cost or when there is not a large enough supply, ideally in a transparent manner.) Once an expanded access policy is anticipated and developed, the second key principle the group identified was making the policy accessible to all individuals who may qualify. First, for patients, with guidance from their treating physician, the company making the drug should always steer the patient to enter a clinical trial (if they meet eligibility criteria). If the contacted company cannot accommodate the patient, they should steer them to other open trials if possible, even if sponsored by another company. Many of our participants noted that this already occurs. The group was particularly cognizant of the disparity in access to drug companies and their expanded access programs: patients with savvy social media strategies are more likely to succeed in navigating across organizational constraints than without similar sophistication. The group believes that increased accessibility would assist in making opportunities for expanded access more equitable. In addition, these policies could help educate patients and physicians about submitting legitimate expanded access requests and help decrease the costs of reviewing inappropriate requests on the company (for example, if there are other proven therapies or the situation is not life threatening). If the patient is ineligible for a trial, the patient should be able to easily access the written expanded access policy online. For example, both large and small companies like Pfizer, Bristol-Myers Squibb, Shire, and Merck post their expanded access policies on their websites, though the terminology may in some cases be complex. In addition, Janssen has developed a video explaining their policies in non-technical terms. Ideally, such policies should be available in some web based or public facing platform to both patients and physicians and written in a clear manner that is jargon free and accessible to individuals at various education levels. Most participants felt strongly that requests for expanded access should originate from a medical provider, not from a patient, since expertise is needed to first screen appropriate candidates. This is consistent with current FDA regulations for an IND, in which a physician or qualified medical expert must sponsor an IND or serve as an investigator under an existing IND for expanded access. Third, companies should have accountability to the requesting party for expanded use requests that they receive and review them within a specified, transparent amount of time. If the request could not be approved, the company should consider clear communication and provide an explanation of why the request was turned down. In these cases, some participants suggested that the company might also consider instituting an appeals process by which a patient can receive an additional review if not approved, potentially from a non-binding third party such as an independent, multidisciplinary body or a regulatory agency like the FDA. (Two participants, however, were uncomfortable with any third party review.) Companies can track expanded access requests in order to guarantee that the patient has received follow-up and that the communication loop has been closed. One large pharmaceutical company conducted an internal audit of its expanded access procedures and found that the largest problem was that employees did not know where to find information. Another representative noted that it is important to maintain consistency across patients and the process of requesting a drug. The final principle would encourage companies to release timely analysis of data from expanded access patients. In addition to tracking communication, companies should keep a database of the number of requests and outcomes, in a manner that doesn’t slow getting drugs to needy patients rapidly. One company refined its internal tracking tools to determine who was requesting drugs, for what conditions, and where they lived. Where possible, companies might be encouraged to share anecdotal or preliminary safety or efficacy data from expanded access in peer-reviewed or other refereed venues in a prudent time frame following collections, if this is available or known. This is not always possible, because emergency INDs do not require provision of safety or outcome data to the company. There are several challenges associated with operationalizing this in the current model, namely the appropriateness of anecdotal data, the level of detailed safety and efficacy data currently available through expanded access, suitability for publication, and funding for these activities in the current budget climate. One potential approach to address this is funding from federal or state regulatory agencies or payers for the reasonable costs of follow-up and reporting outcomes. Regulatory Considerations The participants then discussed the types of risks, including regulatory and financial, that may affect companies’ expanded access policies. When a company is considering expanded access requests, they consider the risks-benefits of providing the drug outside of a clinical trial as well as the potential for any regulatory issues in an era of litigation and an increased threshold for demonstration of safety. While a company’s provision of a drug for expanded access is voluntary, the FDA does require the company to collect and report safety data. Notably, none of the representatives felt that the FDA is a major regulatory barrier to processing and approving expanded access requests once the sponsor has reviewed the request, assessed the benefit-risk, and determined the request meets FDA requirements and evidentiary standards. In addition, the attendees felt that adverse effects and related liability risk were not of particular concern given that the drugs are assessed on a risk-benefit analysis. However, companies that make drugs in particularly limited markets with small numbers of patients (for example, for unusual diseases with less than 200,000 patients nationwide which may justify a special designation called “orphan status”) may be more concerned about restrictive labeling if an unusual adverse event occurred even in one or two patients during expanded access of an orphan or small market therapy. However, there is no data of which participants were aware and no public reports that an adverse event during expanded access has harmed regulatory approval.[x] The group opinion was that that safety data would be available eventually in any event and an FDA “safe harbor” provision would not necessarily affect companies’ willingness to accept more requests for expanded access. A final concern was that there is no regulatory mechanism to consider data from expanded access in the evidence generation process for approval. An Expanded Role for the FDA While the FDA may not serve as a strong barrier to expanded access, the group considered strategies to promote equitable and fair access. For example, some argued that the breakthrough or priority review categories for FDA review might identify products that could have high potential for expanded access requests. This designation expedites “the development and review of drugs for serious or life-threatening conditions.”[xi] As of mid-April 2014, the FDA had received nearly 180 requests for breakthrough designation, with 44 requests granted.[xii] By hastening the drug development process, the FDA has already begun to bring drugs that have a reasonable expectation of benefit to the market faster. In order to receive breakthrough therapy designation, current legislation might be amended so companies could be asked to provide evidence that the 4 A’s are being followed in some capacity. The FDA might also assist companies in establishing expanded access programs during open clinical trials in two main areas: process and capacity building. First, in terms of process, the FDA could be asked to create a defined path for regulatory approval with provisions that would encourage companies, both large and small, to include plans for expanded access programs when developing a drug. While FDA’s draft guidance related to INDs notes that larger expanded access programs could threaten enrollment in clinical trials,[xiii] and some participants agreed that this was a significant issue, not all companies have had difficulties enrolling patients in both clinical trials and expanded access programs. For example, one large pharmaceutical company left a Phase 1 clinical trial open for a promising therapy while concurrently enrolling individuals who didn’t qualify for open clinical trials into an expanded access program, without appreciable leakage of enrollees in their advanced phase trials that might affect the key development pathway. Second, the FDA could support convening around capacity building and sharing best practices with companies. With the understanding that there are many small biotechnology or pharmaceutical companies with limited budgets and staff, the FDA could foster a partnership of large and small companies. This partnership could be achieved by convening meetings where companies share their experiences in creating and sustaining expanded access programs. This could be supported by creating a database for these shared ideas, as well as any expanded access data that can be made legally available, such as how many requests are granted or patient outcomes. To ensure equitable, consistent, and transparent review of requests, some companies suggested the use of an impartial external advisory board. Similar to an unbiased review from an institutional review board (IRB), this committee could have an advisory or decision making function. Companies with supply constraints may feel that if they cannot give the drug to everyone who requests it, then they should give it to no one. This committee could help the company triage the patients who would benefit the most, and would be protected from liability. Next Steps The most efficient and equitable way to make new effective treatments to the largest number of needy patients is regulatory approval, accelerated or otherwise, following successful demonstration of efficacy and safety for a given indication in a specific population. Until that process is complete, access to an experimental therapy is by definition an additional risk, as the agreed necessary safety and efficacy have not yet been demonstrated. True informed consent in this setting is difficult to obtain (i.e. studies have shown that severely ill patients, such as those with life-threating circumstances requesting expanded access, had less retention of information discussed in the informed-consent process and less-clear understanding of the risks of therapy compared to healthier patients[xiv]). One position companies and regulators can consider is that the default answer to expanded access requests should be affirmative, unless there are compelling reasons for not approving requests to patients with life-threatening illnesses. (Such reasons, for example, might include limited treatment supply or lack of reasonable expectation of benefits versus risks.) Such a position would require, however, that there be broader industry, clinician, regulatory, and patient advocacy agreement of shared principles. This paper outlines the experiences, structural principles, and regulatory considerations of a small group, but further meetings may convene a broader group of stakeholders to build upon these concepts. Such consensus-based approaches might lead to durable systems that meet the needs of desperate patients who have run out of options—while allowing innovation to continue to benefit those who may come afterwards. Acknowledgements: We are grateful for the participation of the following representatives in the roundtable: Jeff Allen (Friends of Cancer Research), Michelle Berrey (Chimerix), Renzo Canetta (Bristol-Myers Squibb), Anne Cropp (Pfizer), Joseph Eid (Merck), Aaron Kesselheim (Harvard Medical School), Howard Mayer (Shire), Jeffrey Murray (FDA), Lilli Petruzzelli (Novartis), Amrit Ray (Janssen), and Robert Truog (Harvard Medical School). We thank Mark McClellan (Brookings Institution) for helpful discussions of this topic and comments on the manuscript, and to the Richard Merkin Foundation for support. The views and opinions expressed in this article were interpreted and organized by the staff of the Brookings Institution. They do not necessarily reflect the official policy or position of any individual roundtable representative, their companies, or their employers. References [i] Gaffney, A. Regulatory Explainer: FDA's Expanded Access (Compassionate Use) Program. Regulatory Focus. 2014. Available from: Regulatory Affairs Professionals Society. Washington, DC. Accessed May 7, 2014. [ii] U.S. House of Representatives. 113th Congress, 2nd Session. H.R. 4475, Compassionate Freedom of Choice Act of 2014. Washington, Government Printing Office, 2014. [iii] FAQ: ClinicalTrials.gov- What is “Expanded Access”? U.S. National Library of Medicine Web site. https://www.nlm.nih.gov/services/ctexpaccess.html. Published October 24, 2009. Accessed May 19, 2014. [iv]Food and Drug Administration. Expanded Access to Investigational Drugs for Treatment Use. Fed Register. 2009;74;40900-40945. Codified at 21 CFR §312 and §316. [v]Investigational New Drug Application. U.S. Food and Drug Administration Web site. Published October 18, 2013. Accessed May 19, 2014. [vi] Draft Guidance for Industry: Expanded Access to Investigational Drugs for Treatment Use—Qs & As. U.S. Food and Drug Administration Web site. Accessed May 19, 2014. [vii] A Multicenter, Open-label study of CMX001 treatment of serious diseases or conditions caused by dsDNA viruses. ClinicalTrials.gov Web site. http://clinicaltrials.gov/ct2/show/NCT01143181 Accessed May 19, 2014. [viii] Lane, JM. Progressive Vaccinia in a Military Smallpox Vaccinee—United States, 2009. Morbidity and Mortality Weekly Report. 2009. Centers for Disease Control and Prevention, Atlanta, Geo. Accessed May 7, 2014. [ix] Ryan, DP et al. Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 given as a 1-hour intravenous infusion in patients with advanced solid tumors. Clin Cancer Res 2004: 10; 2222. [x] Usdin, S. Viral Crossroads. BioCentury. March 31, 2014. Accessed June 10, 2014. [xi] Frequently Asked Questions: Breakthrough Therapies. U.S. Food and Drug Administration Web site. Accessed May 19, 2014. [xii] Breakthrough Therapies. Friends of Cancer Research Web site. http://www.focr.org/breakthrough-therapies. Accessed May 19, 2014. [xiii]Draft Guidance for Industry: Expanded Access to Investigational Drugs for Treatment Use—Qs & As. U.S. Food and Drug Administration Web site. Published May 2013. Accessed May 19, 2014. [xiv] Schaeffer MH, Krantz DS, Wichman A, et al. The impact of disease severity on the informed consent process in clinical research. Am J Med 1996;100:261-268. Downloads The Four A's of Expanded Patient Access Authors Darshak SanghaviMeaghan GeorgeSara Bencic Full Article
atm The Rohingya people need help, but Aung San Suu Kyi is not to blame for their mistreatment By webfeeds.brookings.edu Published On :: Fri, 25 Aug 2017 19:27:16 +0000 Full Article
atm Utopian sewage treatment plant & educational center gets poetic By www.treehugger.com Published On :: Thu, 13 Sep 2018 14:23:46 -0400 Infrastructure doesn't have to look boring; this one references an old fable about a mountain utopia and features a modular steel frame. Full Article Design
atm Injecting Aerosols Into Atmosphere to Slow Global Warming Environmentally & Economically Risky By www.treehugger.com Published On :: Mon, 18 Apr 2011 11:00:00 -0400 Another report on another geoengineering method that is likely too risky to try and utterly not cost-effective: Injecting aerosols into the atmosphere to slow warming (which would do absolutely nothing about ocean acidification, by the way). Full Article Technology
atm Financial, Energy Costs of Scrubbing CO2 Directly From Atmosphere Grossly Underestimated By www.treehugger.com Published On :: Mon, 12 Dec 2011 11:02:00 -0500 Reducing CO2 emissions at the source, or better yet, not emitting them in the first place, is the better option. Full Article Technology
atm A Tale of Two Geoengineering Experiments: Ocean Iron Fertilization & Injecting the Atmosphere By www.treehugger.com Published On :: Wed, 18 Jul 2012 17:30:00 -0400 The first field test of injecting sulfate particles into the atmosphere is proposed for New Mexico; ocean iron fertilization experiment shows more promise than previous ones. Full Article Science
atm Humans are warming atmosphere and climate change is irreversible unless we act now. By www.treehugger.com Published On :: Fri, 27 Sep 2013 09:59:12 -0400 The Intergovernmental Panel on Climate Change (IPCC) has released its fifth assessment report (AR5), which surely must be one of the most important science documents of all time. Full Article Science
atm Radioactive Waste Is Piling Up in Japanese Sewage Treatment Plants, Some Sold as Fertilizer By www.treehugger.com Published On :: Sun, 04 Sep 2011 19:52:17 -0400 The disaster at Fukushima may have faded from the news cycle, but the radioactive waste it left behind isn't going anywhere. At the Saitama sewage treatment plant, 169 miles from Fukushima, workers are dealing with tons of Full Article Business
atm Old CDs could be re-used in sewage treatment By www.treehugger.com Published On :: Mon, 30 Sep 2013 08:01:42 -0400 The disks are coated with zinc oxide nanorods that break apart organic molecules in sewage. Full Article Technology
atm Roundup found in popular oatmeal, granola & kids' cereals By www.treehugger.com Published On :: Wed, 15 Aug 2018 08:12:10 -0400 Weed killer, it's what's for breakfast! Glyphosate found in 43 of 45 conventional oat products tested by EWG. Full Article Living
atm Sentinel-5P puts eyes in the sky to monitor progress in reducing atmospheric pollution By www.treehugger.com Published On :: Tue, 17 Oct 2017 08:00:00 -0400 The successful launch of Sentinel-5P means scientists will soon have access to the most accurate monitoring yet of pollution and climate change related gases in earth's atmosphere Full Article Science
atm Water Treatment System Uses Salt and Electricity to Provide Clean Drinking Water to Thousands By www.treehugger.com Published On :: Thu, 10 Jan 2013 07:00:00 -0500 Providing clean water in areas with minimal local resources may be as simple as implementing this ingenious DIY water treatment system. Full Article Technology
atm Novartis announces FDA approval for Jadenu™ to simplify treatment administration for patients with chronic iron overload - Dr. Elliott Vichinsky on Jadenu By feedproxy.google.com Published On :: 31 Mar 2015 13:15:00 EDT Elliott Vichinsky, MD, University of California, San Francisco (UCSF) Benioff Children's Hospital Oakland Full Article Healthcare Hospitals Medical Pharmaceuticals Pharmaceuticals New Products Services Broadcast Feed Announcements FDA Approval MultiVu Video
atm Study finds changes in treatment have increased life span for childhood cancer survivors - Hear more from Dr. Armstrong By feedproxy.google.com Published On :: 01 Jun 2015 17:15:00 EDT Hear more from Dr. Armstrong Full Article Healthcare Hospitals Medical Pharmaceuticals Children-related News Broadcast Feed Announcements MultiVu Video
atm Abbott's iDesign System Creates 3-D Map of the Eye for Precise, Personalized LASIK Vision Treatment - NASA’s Newest Space Telescope is Calibrated by the Same Technology Used in LASIK By feedproxy.google.com Published On :: 20 Jul 2015 12:00:00 EDT Years ago, NASA’s Hubble Space Telescope launched with an error in the telescope’s mirror, which blurred its images for its first years in orbit. For NASA’s upcoming James Webb Space Telescope that is traveling much farther out in space, there can’t be a mistake. Abbott scientists created a technology to calibrate the mirrors on NASA’s new James Webb Space Telescope, which is now the same technology used in the iDesign System that allows ophthalmologists to map the human eye with great precision for a highly personalized LASIK treatment. Full Article Healthcare Hospitals Medical Pharmaceuticals Medical Equipment Pharmaceuticals Broadcast Feed Announcements MultiVu Video
atm City Of Hope Launches New Campaign To Showcase Innovations In Research And Treatment - Meet Kommah By feedproxy.google.com Published On :: 21 Oct 2015 14:00:00 EDT Meet Kommah Full Article Healthcare Hospitals Medical Pharmaceuticals New Products Services Broadcast Feed Announcements MultiVu Video
atm Gout & Uric Acid Education Society Hosts Roundtable Exploring Strategies for Elevating the Severity of Gout and Improving Access to Public Education and Treatment - Gout as a Serious Health Issue By feedproxy.google.com Published On :: 12 Jan 2016 16:30:00 EST Gout as a Serious Health Issue Full Article Healthcare Hospitals Medical Pharmaceuticals Not for Profit Broadcast Feed Announcements MultiVu Video
atm GOP groups to use Biden sex assault allegation, Kavanaugh treatment against Democrats in key Senate races By www.cnbc.com Published On :: Thu, 07 May 2020 22:54:27 GMT The GOP groups are arguing that Democrats are applying a different standard to Biden, who has denied that he assaulted former Senate staffer Tara Reade in 1993, than they did to Justice Brett Kavanaugh. Full Article
atm Doctors and patients wonder if the NBA is getting special treatment with coronavirus tests By www.cnbc.com Published On :: Thu, 19 Mar 2020 23:23:02 GMT Sick patients are being turned away, unable to receive tests because they simply aren't available. In a stark contrast, the NBA said that as of Wednesday, at least eight teams had been tested for the COVID-19 coronavirus. Full Article
atm Stem cell treatment for coronavirus symptoms being trialed in the UAE By www.cnbc.com Published On :: Tue, 05 May 2020 09:32:20 GMT Dr. Fatima al-Kaabi of the Sheikh Khalifa Medical City discusses a stem cell treatment currently being tested for its efficacy in alleviating coronavirus symptoms, and the easing of the lockdown in the UAE. Full Article
atm Teva CEO Kare Schultz on coronavirus treatment and a possible second wave By www.cnbc.com Published On :: Thu, 07 May 2020 17:22:27 GMT Kare Schultz, CEO of Teva Pharmaceuticals, joins "Squawk on the Street" to discuss the coronavirus pandemic and potential treatments. Full Article
atm I, Batman's Armor, Am Voting Trump By www.somethingawful.com Published On :: Mon, 30 Mar 2020 12:00:00 GMT You’ve pushed me too far this time. While I was out here taking LITERAL BULLETS for Gotham City’s greatest hero, all you CUCKS can do is point and laugh. Full Article
atm Antibodies From a Llama Named Winter Could Help Scientists Find a Treatment For COVID-19 By feedproxy.google.com Published On :: Thu, 07 May 2020 08:00:00 PDT The hunt for an effective treatment for COVID-19 has led one team of researchers to find an improbable ally for their work: According to US and Belgian scientists, a four-year-old llama named Winter who lives in a secret location in Belgium could hold the key to a cure and help scientists find a treatment for COVID-19. The team — from The University of Texas at Austin, the National Institutes of Health and Ghent University in Belgium — reports their findings of a potential avenue for a coronavirus treatment involving llamas on May 5 in the journal Cell. Full Article llama cure covid-19
atm What would a game-changing treatment for coronavirus look like? By www.newscientist.com Published On :: Fri, 17 Apr 2020 16:45:53 +0000 Even if we find drugs that are effective against the coronavirus, that doesn't necessarily mean they will change the wider situation and help end lockdowns Full Article
atm Ripples in Earth’s atmosphere make distant galaxies appear to flash By www.newscientist.com Published On :: Wed, 22 Apr 2020 10:00:59 +0000 Faraway galaxies have been spotted unexpectedly flashing up to 100 times their usual brightness, and it seems to be caused by eddies in Earth’s atmosphere Full Article
atm Coronavirus: Johnson reveals 'contingency plans' made during treatment By www.bbc.co.uk Published On :: Sun, 03 May 2020 12:29:09 GMT Boris Johnson says doctors had planned what to do if his coronavirus treatment went "badly wrong". Full Article
atm Coronavirus: DIY hair shaving and beauty treatments By www.bbc.co.uk Published On :: Fri, 17 Apr 2020 07:15:21 GMT As hair dye and clippers become the next thing on the stockpile list - we look at how people are managing their hair and beauty. Full Article