Tuesday, May 24, 2005

The Senatorial Compromise

I am so disappointed on this Senate compromise. Here's some of my thoughts, that I think you will share. A problem with this deal is that the Democrats did not what to be put in a position where they would have to filibuster Janice Rogers Brown in particular Boxer and Finestein. They do not want to be accused of being as anti-minority or anti-civil rights. This gets them off the off the hook with their black & women minority constituents and furthermore somewhat insulates them from their radical moveon.com base by allowing them to say that they had to compromise to avoid the filibuster rule change which would have occurred otherwise. This weakens the President/executive branches power by sending Pres. Bush a message/warning that he should consult with Dems prior to nomination of a Supreme Court Judge. The new heroes and leaders of the democrats are the gang of seven who will become the new microphones of the democratic party. Americans are tired of listening to Byrd, Schumer, and that bore Harry Reid so with these new guys which are considered heroes now have gravitas to speak authoritatively on left wing/secular issues.

From the Republican side, Senator McCain is the de facto leader of the Republican Senate and getting back at Bush for losing the party nomination in 2000. This strengthens his hand for the Republican Nomination in 2008.

This was a brilliant political chess move make by the Democrats for they give up nothing. They can still filibuster when/if a pro-life and devout Christian is nominated. They are off the hot seat regarding the Political Correctness question regarding women and blacks vis a vis Qwens and Brown. They stop the bad press that is generated by the virtual shut down of the government's business caused by this preoccupation with the Judiciary. Its a win for the Dems thru and thru.
The Republicans have rolled over and make me wonder if it really matters that the Republicans control the Legislative and Executive Branches if they won't flex their muscles against the Kennedy and Boxer crowd. They agreed to not consider changing rules for 1 1/2 years!Question: Do you think if the Dems controlled the Legislative and Executive Branches the minority Republicans would have been able to pull off a slick move like this? I do doubt it and in fact I don't think they would have had the manipulative genius to even try.

With all due respect, I think George Will is wrong. The filibuster or Senate rule XXII has been changed like 6 or 7 times since its inception in 1917 and always by the Democrats. George Will fails to see that the President has a constitutional responsibility to nominate to the Judiciary and the Senate a constitutional obligation to vote them up or down. The rule change would have only dealt with Filibuster/Cloture on Judicial Nominees ONLY! Up until Pres. Bush came into office 51 votes were required but now 60 are required to approve Judicial Nominees. This entire exercise shows that tyranny of the minority rules in our country. Its a sad day for this was a bad compromise by the Republicans even if it wins in the court of "public opinion" of the MSM. The only ones who really like this are the Democratic leaders and the MSM. That makes me wonder? Democratic strategy for future power seems to lie Judicial Imperialism as you have often said. With this deal they live to fight many future battles and with this precedent have raised the filibuster bar even higher because it fortifies the "Senatorial Tradition" argument.

The Republicans agreed to but their gun(Constitutional Option) in the closet for a year and 1/2 while let the Dems keep the gun(Filibuster) in their hands if they promise not to us it! Where's the wisdom in an agreement like that?

Thursday, May 19, 2005

Journalistic Jihad and the New World Dis-Order"

There is no God but the First Amendment and MSN Journalist are its Prophets! Those of us who graduated from a university school of Journalism are the Caliphs and Mullahs of our American Secular Nation and Governmental System. We Journalist are the arbiters nay the Spiritual leaders or Sufis of our Society. We bow down to no one not even the Leader of the Free World, the President of the United States nor his representatives! The pecking order of our fellow reporters is based on the ranking of the Theological Journalistic Seminaries we graduated from and our blue blooded pedigree is further enhanced if we have been a reporter on the ground in Iraq, part of the White House Press core or work for either PBS or the Mainstream Media! We members of the Media belong to what our founding fathers envisioned as the "Fourth Estate" or the fourth branch of Government and to be honest our wise professors and mentors have taught us that we are like the Pope the "First Among Equals"! So back down Presidential Spokesperson Scott McClellan! And Mr. President do not presume to edit us, the sacrosanct members of the Press and the Almighty "Fourth Estate" and do thou dare to tell us what to write about and report on?.... Your Blasphemy will be remembered as Journalistic "Infamy"! Especially, Mr. President don't presume to tell us to report on the lengths that the US military has gone to in order to treat Islamic detainees and their "Holy Qur'an" with respect, for the Military are vile dirty infidels and they are incapable of doing anything with nobility. In particular writing about the US Military in a favorable light is worse than the journalistic Cardinal Sin of plagiarism and would be grounds for excommunication from our the Fraternity of Journalism. It is Anathema to tell the truth to the world about the respect and restrain the US Military shows toward the Qur'an.
We members of the MSM and Press are like the Sunnis of the Muslim world because we represent the largest group in journalism and like the Sunni follow the Caliphs or elected Mullahs of the Islamic Intelligentsia. Those conservative Journalist who graduated from University Schools of Journalism although they have somewhat of a valid claim to membership in the "Fourth Estate" because of their Degrees are in reality heretical for like the Shia, whom we the Sunni sect of Journalism consider heretical, since they claim that the authentic Imams and Ayatollahs of Islam belong to the lineage of Imam Ali Ibn Abi-Talib, the cousin and son-in-law of the prophet Mohammad.

These "Neocon" Shia like Journalist are firebrands who can trace their spiritual lineage to Barry Goldwater, Ronald Reagan and the lies of conservatism propagated by National Review's founding heretic extraordinaire William F. Buckley. Yes we the Sunni sect of Journalist who have Bill Moyers as our spiritual leader, are engaged in a Holy War with these other sects of conservative journalism. Those Bloggers and Talk Show New Media Types are truly vulgar and vile for they have no rightful claim to membership in the Press Corp for they have no Journalistic Heritage whatsoever. They are Plebeians and the fruits of their work have the catastrophic impact of Muslim Wahabis terrorists. These commoners sow their violent heresies' among the masses causing irreparable damage to our Secular, Liberal and Socialist Agenda. Like the Fundamentalist Wahabi Barbarians in their street clothes, these Pajama Clad Literary Mercenaries disseminate their dangerous ideas throughout American by circumventing the Ecclesiastical Main Stream Venues of Journalism and do not have the Imprimatur of the New York Times nor other MSM outlet.
These so called Bloggers or Pajama Clad Friars are like First Amendment Heretics and are followers of the Blogging equivalent of the Rebel Abu Musab al-Zarqawi on Salem Radio Network aka Hugh Hewitt!
These peasant bloggers/journalist are like weeds reeking havoc on our "Fourth Estate" gardens and vineyards undermining our goal to create a New World Order. An Order were God is not the Judeo-Christian one but the new Irreligious God of Egalitarianism based and founded on Liberal Philosophy!
We prophets and practitioners of Journalistic Orthodoxy have as our secret ambition the ultimate demise of the "Great Satan" otherwise known as the brave volunteer US Military by attrition. This we will achieve by insidiously infecting the consciousness of those in the University and TV land and are Americans who might otherwise want to join the Military and fight for these bloggers and First Amendment Blasphemers. These First Amendment Heretical Jihadist Bloggers and Radio Talking Rogues are out flanking us..... Those of you who aren't spiritual descendants of Bill Moyers, Mareen Dowd, Paul Begala, Harold Raine's and Dan Rather beware for we represent Journalistic Orthodoxy and have the equivalent of Holy Orders from our Schools of Journalism. We are the Printing Press Templar Knights of the Order of the First Amendment and only we carry the weight of an Imprimatur. We the members of the "Fourth Branch" are First Among Equals in American Politics and all others are impostors and misguided zealots!

This is parody of what a psychoanalytical peek into the Mind of a Main Stream Journalist who wants to create what I would characterize as a "New World Dis-Order" brought into fruition by the western elites whom Lenin regarding as "Useful fools"!

Francis X. Yubero, M.D.

Wednesday, May 04, 2005

Saving Amanda and the Anatomy of A Compassionate Use Drug Program for Medarex

Amanda a 22 year old young lady who suffers from Hodgkin's Lymphoma, a form of cancer, has had recurrences after it was diagnosed in 1998 when a mass the size of a submarine sandwich was found behind her heart in the thoracic cavity (www.tinyurl.com/9ukyk). Initially treated with chemotherapy and after a recurrence she underwent a bone marrow transplants. In spite of this state of the art treatment which has saved so many cancer victims she subsequently had a recurrence. However, there is one last promising possibility to combat this tenacious form of Hodgkin's. CD 30 a drug currently in Phase II clinical trials being run by the Pharmaceutical company Medarex www.medarex.com could be this last chance. New approaches involving the use of antibody-based agents have produced promising results in experimental Hodgkin's lymphoma models. Early clinical trials using immunotoxins, radioimmunotherapy (RIT), bispecific molecules and monoclonal antibodies (mAbs), have demonstrated some clinical efficacy in patients with advanced refractory Hodgkin's Lymphoma. Although it seems unlikely that these approaches alone will cure chemotherapy-resistant patients with larger tumor masses, combination with conventional chemotherapy may help to overcome resistance of Hodgkin-Reed/Sternberg (H-RS) cells or to eliminate residual disease. Since H-RS cells are extremely sensitive to irradiation, RIT may be a potential approach. CD 30, is a monoclonal antibody or a humanized and a fully human anti-CD30 mAb is currently being evaluated in phase I/II clinical trials. These monoclonal Antibodies could engage the human immune system against the Hodgkin's Lymphoma and are capable of directly inducing apoptosis of H-RS cells. In addition, these monoclonal antibodies could be combined with conventional chemotherapy and are thus promising candidates for further development for the therapy of Hodgkin's Lymphoma.

The Food and Drug Administration(FDA) puts potential drugs and medical devices for all diseases through a rigorous set of clinical trials process known as Phased Clinical Trials before it will approve them for use with patients in the United States. These clinical trials are essential to the development of novel and improved treatment approaches for not only patients with cancer, but other diseases as well. Drug testing must go through 4 distinct phases of clinical trials to earn FDA approval.

Phase I trials are the earliest formal phase of clinical trials when testing a drug for treatment in humans and are done to find out the following: 1) the safe dose range and/or scheduling of the specific treatment regimen, 2) the side effects, 3)how the body copes with the drug, 4) the combination of drugs necessary for treatment.If the treatment shrinks cancer. The information from Phase I is used to established doses or scheduling of the drug, as well as its ability to produce anti-cancer responses, are utilized in subsequent trial phases.

Phase 2 or (Phase II) occurs with approx. 70 out of every 100 new treatments tested in phase 1. This series of trials may be done on people who either all have same the type of cancer or with several different types of cancer. Phase 2 trials determine if the new treatment works well enough to proceed on and test in phase 3. Questions that are answered include 1). which types of cancer it is the drug effective against, 2). more info about the side effects and how to manage them, 3.) more info about the most effective dose to use. Phase 2 trials are often larger than phase 1 and there may be up to 50 people taking part. If the results of phase 2 trials show that a new treatment may be as good as existing treatment, or better, it then moves to phase 3.

Phase 3 (phase III) trials compare the new treatments with the current standard or state of the art treatment available. Phase 3 trials are usually much larger than phase 1 or 2. This because differences in success rates may be small so, you would need very many results to show the difference. For example, 6% more people get a remission with a new treatment compared to standard treatment. If a phase 3 trial gave the new treatment to 50 people and the standard treatment to 50, on average, there may be 3 more remissions in the new treatment group. The 2 groups would not look that different. If they gave each treatment to 5,000 people, there could be 300 more remissions in the new treatment group. Sometimes phase 3 trials involve thousands of patients in many different hospitals and even different countries. Phase 3 trials are usually randomized which means the researchers put the people taking part into 2 groups at random. One group gets the new treatment and the other the standard treatment.At the end of this Phase information is processed and reviewed in what is know as a meta-analysis which consists of combining all the results from the phase 3 trials of a new drug or treatment. The purpose is to get a broader picture of how well a treatment works. Obviously the more data or information you have, the more accurate the results are likely to be. At the end of this Phase the drug or treatment is approved and the company receives its license.

Phase 4 (phase IV) trials although helpful are really is not necessary for they are carried after a drug or treatment has been shown to work and has been granted a license. The purpose of Phase 4 is to provide the pharmaceutical company with the info it will need to help market this newly licensed drug with the physicians and the marketplace. The main reasons pharmaceutical companies run Phase 4 is help then crystallize the information by:1). learning even more about the side effects and safety of the drug, 2). determining in more detail what the long term risks and benefits are, 3). and finally gain more insight into how well the drug works when it’s used more widely than it was in clinical trials.

CD 30 has completed the Phase 2 stage and truly more than half of Medarex's FDA quest for approval is over and the drug is well on its way to being used clinically barring any unforeseen disasters. From this moment on tweaking and refinement of the drug and its usage is the company's focus. Promising drugs as of 1997 have been "fast tracked" by the FDA. This means that it has determined that the drug or biologic is intended for the treatment of a serious or life-threatening condition. Furthermore having demonstrated the potential to address unmet medical needs for such a condition, the FDA will facilitate and expedite the development and review of the application for the approval of the product. As a matter of fact Medarex has a vaccine (MDX-010 in combination withMDX-1379, a melanoma vaccine, for the treatment of previously treated, unresectable Stage III and Stage IV metastatic melanoma) for a form of skin cancer, fast tracked in October 2004(www.tinyurl.com/9pdu3).

Compassionate Use Programs and FDA protocols for drugs or biologics in the midst of Clinical trial testing is another possibility which can help patients receive treatment before finally being released. A formal compassionate use program is a mechanism for getting an unapproved but promising new treatment to patients who would otherwise be unable to receive it. Compassionate use programs are for people who have a life threatening with "no comparable or satisfactory alternative drug or other therapy available to treat that stage of the disease in the intended patient population" (in the words of the FDA regulations). Formal compassionate use is a bit like a clinical trial in that you will still have to meet specific requirements such as the type and stage of disease, and usually you must be treated by doctors who participated in the clinical trials for the drug, but compared to trials, the requirements are somewhat relaxed. If you qualify for an open clinical trial of the treatment, obtaining it through compassionate use is not an option.

According to the FDA regulations, compassionate use programs are normally for drugs which are in phase III or have completed accrual to their trials (it takes significant time to allow the data to mature, compile it, and get it reviewed by FDA - often several years), but the regulations do say compassionate use might be possible for some drugs which are only in phase II testing. I presume there would still have to be applicable promising results - such as spectacular results from an ongoing phase II trial. If you just heard about the latest cancer cure for mice on the nightly news, it is likely that there will not be a compassionate use program. If there are reports of success in trials with your form of cancer most likely the company will have a Compassionate Use Program.

Although the FDA has to approve compassionate use programs, they normally do so without fuss. Whether there is a compassionate use program largely depends on whether the drug company has decided to have one. The decision depends on many factors including the cost which can easily run into the millions and whether there is an adequate supply of the drug (which is often an issue). In the past, campaigns by organized patients has sometimes made the difference. For instance, Genetech granted expanded access to the breast cancer drug, Herceptin, only after breast cancer activists conducted an intensive campaign. ("Demand Grows for Early Access to Promising Cancer Drugs",Journal of the National Cancer Institute, November 20, 2002). When a drug company decides to provide access to their unapproved drug outside of the clinical trial they most commonly do it in the following two ways:

1.) Expanded Access Programs (EAP): Drug companies in the late stages of drug development including the Phase III clinical trial stage, can offer Expanded Access Programs for patients who are not able to enroll in a clinical trial. The FDA generally approves these programs if the drug has demonstrated some effectiveness against a specific cancer in the on-going clinical trials.
2.) Single Patient Access(SPA): Patients who are not eligible for either clinical trials or an Expanded Access Program (if one exists) may be eligible to receive the unapproved new drug by applying for Single Patient Access. In this situation, the patient's doctor must first request permission for access to the drug from the drug company. If the company agrees, the patient's doctor works with the drug company to apply for FDA approval for use of the drug for the patient. The timeline for Single Patient Access varies. In an emergency, the FDA can walk the paperwork through in 24 hours.

Hopefully Amanda, this vivacious and courageous young women will have her plea for CD 30 honored by Medarex. Medarex will receive a tremendous amount of good publicity for free if they decide to go out on a limb for this young lady. This is a small biopharmaceutical company with just over 400 employees. The millions of dollars of publicity it will receive for free may bring this company notoriety and investors! In addition the FDA will easily support a Compassionate Use Program if Medarex decides to comply. Medarex, as a Medical Doctor I urge to help out this courageous young women, Amanda, who has been valiantly fighting refractory Hodgkin's Lymphoma for 7 years. It must be kept in mind that it cost pharmaceutical companies in the vicinity of 2 billion dollars to take a drug from conception to market. The road to market is expensive, tortuous and unbelievably difficult and is fraught with medico-legal gauntlets. Not withstanding the medico-legal and financial issues faced by all of us in the health care field, helping Amanda is simply the Hippocratic thing to do! Cheers to Medarex!

Francis X. Yubero, M.D.