Disclosure of New Clinical Drug Trials to the Community

Editor's Note: For an additional article on a related topic please see our article " Release of Clinical Drug Trial Study Data" and also Clinical Drug Trials and Risks

(9/19/16)- The Department of \Health and Human Services (HHS) and the National Institute of Health (NIH) have promulgated the final rule on www.nih.gov for clinical trial registration and follow-up on www.clinicaltrials.gov . The NIH site contains the press release dated September 16, 2016.that links into the new rule. There are now over 230,000 clinical trials listed on that site. .

The clinical trials listed on the site contain data on drugs, biologics and medical devices being tested. Negative results as well ae positive results will have to be included, subject to loss of funding from the agencies.

(6/29/15)- The scientific journal Science, one of the leading publications in that field posted the most comprehensive guidelines for the publication of studies in basic science, calling for the adoption of defined rules on sharing of data and methods.

The new guidelines, called TOP for Transparency and Openness Promotion, call for a systematic approach that can be applied by all scientific journals to all scientific fields.

(4/30/09)- Coast Independent Review Board LLC of Colorado Springs, Colo., the company discussed in our items dated 4/24/09; 4/3/09 and 3/21/09 below, announced that it would be closing down its operation.

FDA officials met with the company at its headquarters in Colorado Springs to discuss how to avoid disruption for patients and for companies conducting clinical trials with Coast-organized review boards. As we noted below, there are over 300 clinical trials that the company is presently overseeing, so it will be a complicated matter that needs to be resolved.

(4/24/09)- Under pressure from the recent House committee hearing and the FDA, as we discussed in out items dated 4/3/09 and 3/21/09 below, Coast Independent Review Board LLC of Colorado Springs, Colo has agreed to temporarily stop approving new clinical trials regulated by the FDA, until it has given the agency an acceptable plan of corrective actions.

The FDA will allow trials now under way to continue, but Coast has agreed not to enroll any new patient in them until the corrective plan is approved. There are currently over 300 clinical trials, involving more than 3000 researchers that Independent is now overseeing.

(4/3/09)- As a follow-up to our item dated 3/21/09 the House Energy and Commerce Committee that is chaired by Rep.Bart Stupak (D., Mich.) heard the testimony of Coast Independent Review Board Chairman Daniel Deuber, who had issued a press release before the hearing in which he accused the committee of "setting up" his company.

"Where was the due diligence of your company" asked Representative Stupak. The hearings brought out the fact that Coast reviewed 356 study proposals and rejected only one in the last five years.

Two other review companies that were called on by the G.A.O., Argus Independent Review Board of Tucson, and Fox Commercial Institutional Feview Board, of Springfield, Ill., refused to approve the Adhesiabloc plan. In their responses, they called the trial design "awful" and " apiece of junk", according to the G.A.O.

The hearings also brought out the fact that the G.A.O. had been able to register a fictitious clinical trial oversight company with the FDA

(3/21/09)- An investigation by the General Accounting Office, conducted at the request of the House Energy and Commerce Committee that is chaired by Rep.Bart Stupak (D., Mich.) has brought into question the integrity of the firms that are hired to oversee the safety to patients of clinical drug trials.

In the "sting" operation a "phony" product was set up by a "phony" company that hired a Colorado company, Coast Independent Review Board to oversee a study of "Adhesiabloc", a product designed to reduce scar tissue after surgery.

In reality, there was no such product, and its developer Device Med-Systems does not exist. The lead researcher for the study, Dr. Jonathon Q Krueger, a Virginia doctor with a four-page curriculum vita also did not exist. Coast was paid by Device to check out the company conducting the trial to make sure the doctors conducting the study are qualified and are in good standing with state medical boards.

Mr. Stupak's committee has been investigating companies and others that monitor the safety of patients in medical studies.

It turned out that the address given by Device, the site where the study was supposed to be conducted was a store that rents mail boxes in a strip mall in Clifton, Va. The Virginia licenses of the physicians conducting the study were fake.

(7/15/05)- We at therubins: have been in touch with the Long Island Clinical Research Associates. For more details about the organization please go to http://www.LIClinical.com. They are presently conducting clinical research studies of gastrointestinal illnesses including GERD, IBD, and more. Please contact Long Island Clinical Research Associates to participate in a trial and receive free treatment and test new medicines. We highly recommend this clinical study association.

(7/4/05)- Help is on the way for laymen trying to understand the meaning of the data from clinical trials of new drugs and medical procedures. Various medical journals and medical professionals have combined to start a new site www.patientINFORM.org, which will provide this information in layman's language.

Though the site does not aim to be a comprehensive guide to all new research, it will choose studies that appear to be of highest interest and relevance to consumers facing decisions about cancer, diabetes or cardiac treatment. Medical journals will have no input in the interpretation of the research.

(6/14/05)- Jeffrey M. Drazen, editor in chief of the New England Journal of Medicine accused Pfizer Inc., GlaxoSmithKline PLC and Merck & Co. of "making a mockery" of efforts to create transparency of information of clinical trials. In September, the 11 members of the International Committee of Medical Journal Editors said they wouldn't publish studies that aren't registered in a public database as they are launched.

The committee announced the details as to what they expect to be revealed by the pharmaceutical companies in their studies. Included in the 20 item details of each study are what the study is designed to evaluate how many patients will be studied and how the company is sponsoring the study. Dr. Drazin said that a review was conducted by Deborah Zarin of the NIH of the material that was released in the clinical database for 10 pharmaceutical companies

"They (the three companies) are giving nonsense details," Dr. Drazen said. "They are written in a way that they are trying to hide what they are doing." The three companies have filed only vague descriptions of many studies, often failing to even name the drugs under investigation.

(3/11/05)-Senator Charles E. Grassley (Rep.-Io.), chairman of the Senate Finance Committee has introduced a new bill in Congress that would create an electronic database with information about clinical trial study outcomes and funding, potential drug side effects, and demographic information on test subjects.

(2/28/05)- The FDA announced that it was creating a board to advise it on drug complications and to warn patients about unsafe drugs. The board will make its conclusions available on a Web site, but it will not have independent power to force the withdrawal of a drug. Senator Charles Grassley (Rep.-Io.) has stated that he would introduce legislation to create an independent panel that would be outside the aegis of the FDA. In his viewpoint, only an thoroughly independent body from the FDA should have the job of dealing with drugs that are already approved and being sold to the public as safe.

The FDA's Office of Drug Safety (ODS) now has about 109 employees. This office analyzes the data sent in by physicians and other medical professionals re the adverse and unsafe reactions that their patients are having to certain medications. It is also the responsibility of the various drug companies to report this information to the ODS.

Dr. Alastair Wood, an associate dean at Vanderbilt University, and the head of the FDA panel that reported recently on the safety of the COX-2 drugs has long advocated an independent safety review board at the FDA structured like the National Transportation Safety Board.

President Bush's budget for 2006 seeks an increase of $6.5 million, or 24% for the ODS, and also calls for the hiring of additional 25 workers. In his budget request the president is also asking for an increase of $81 million for the FDA to a total of $1.88 billion for the agency. This represents a 4.4% over the FDA's budget in 2005.

In nominating the acting commissioner of the FDA Lester Crawford to become the permanent head of the bureau, he has selected a veterinarian who holds a doctorate in pharmacology, but who is not a physician. In addition to having served twice as the acting head of the FDA, Mr. Crawford has also headed the agency's veterinary medicine department, and he also ran the Agriculture Department's Food Safety and Inspection Service.

(2/7/05)- The National Institute of Health (NIH) has issued new rules that ban its scientists from working in either a paid or an unpaid capacity for drug and biotechnology companies, health care providers, insurers, trade associations and educational institutions that apply for money form the agency.

The rules will also ban top scientists from owning shares in drug or biotechnology companies. Lower-level employees will be able to won as much as $15,000 company shares. Gifts greater than $200 will be banned, and scientists will be prohibited from accepting many academic prizes.

The House Energy and Commerce Committee recently uncovered the fact that 30-40 NIH scientists were working as consultants for drug and biotechnology companies, but had failed to inform the agency of the work that they were doing, let alone, get approval for the work.

The NIH has also issued new rules that will require that scientists who have been funded by the NIH to make their published work available within 12 months of publication on a government Web site. Elias Zerhouni, the NIH Director had previously advocated that the work be available with 6 months of publication. Several of the larger commercial scientific journals and some nonprofit organizations had objected to the 6-month time frame.

Dr. Zerhouni stated that, because taxpayer dollar's had funded the research, the material should be available to the public within a reasonable period of time. PubMed Central is the name of the publicly funded NIH Web site. Scientific industry publishers had announced in December 2004 that they would allow a panel of three patient-advocacy groups to select hundreds of timely journal articles and to make the content available through the groups' Internet sites. The organizations are the American Cancer Society, the American Diabetes Association and the American Heart Association. The publishers include Reed Elsevier PLC, John Wiley & Sons Inc., Blackwell Publishing and others. The consortium, called patientINFORM, is expected to launch the project in the spring.

Dr. Eric Topol, chairman of cardiovascular medicine at the Cleveland Clinic, one of the nation's most prominent medical researchers announced that he would be severing his ties to most of the companies that he has been involved with. Dr. Topol said that he still hoped to collaborate with drug and device companies, but without compensation, because that enables him to keep up with advance medicine.

Dr Topol stated, "I want to ensure that my own and the institution's academic integrity as is chief academic officer remain beyond even any appearance of a perceived conflict of interest." The doctor went on to state that he has sent letters to all companies that he was associated with, informing them of that decision. He will however remain on the scientific advisory board of Perlegen Sciences, a California company he described as on "the leading edge of genomics." He will give up all pay and stock options that he receives from the company.

He went on to note that top officers of the National Institutes of Health were being made to give up consulting relationships with companies. "I believe that model is something that should be done across all academic medical centers," he said.

(1/26/05)-Britain's health minister said British regulators would begin collecting and publishing online patient reports of drug side effects. The Medicines and Healthcare products Regulatory Agency (MHRA) will oversee the new British program. The agency said patient feedback will be collected online and on printed forms to be distributed in doctor's offices. Basic data about adverse reactions will then be published online.

A larger database will be available to researchers as long as they conduct ethically and scientifically sound research and agree to protect patient confidentiality. The U.S. Food and Drug Administration also collects feedback on drug side effects by does not maintain a publicly searchable database of the data. Consumers can request access to the information on an individual basis.

(1/13/05)-Four trade groups representing the world's biggest drug makers said that they would voluntarily increase the data available to the public in connection with clinical trials of drugs. The groups included the Pharmaceutical Research and Manufacturers Association in Washington and organizations in Europe and Japan.

Under the industry plan, a company starting a drug study would list certain information about it in a public database operated by the National Library of Medicine at www.clinicaltrials.gov . Phase 1 trails of drugs would be specifically excluded from the database. Initial tests of a potential drug that examines its safety and biological activity would not be listed.

(12/04)-The issue of possible conflict of interest keeps on rearing its ugly head in connection with many matters involving medical professionals and their affiliations. When a panel for the National Institutes for Health recommended increased usage of statin drugs, it was determined that a majority of the panel members had financial ties to companies making these drugs.

A recent edition of Fortune magazine pointed out that Dr. Eric Topol, chairman of cardiovascular medicine at the Cleveland Clinic, and the leading critic in pointing out the cardiovascular risk for Merck's Vioxx, was a paid advisor to a hedge fund that had shorted the stock. The hedge fund profited substantially when Merck stock dropped about 35% this year.

Dr. Topol has been a critic of the drug since 2000, and began advising the Great Point Partners, LLC hedge fund in 2003. In a letter to its shareholders the fund pointed out that "Eric Topol M.D. of our Medical Advisory Board, has been singing this tune (pointing out the risk of Vioxx) since 2002, and we were on the right side (short) of that situation".

Dr. Topol said he was paid only $12,000 a year by Great Point, did not invest in the hedge fund and did not know the fund was short Merck. He also stated that he did not know that his name was being used in promotional material being distributed by the fund. He also stated that he has resigned from the advisory board of the fund as soon as he heard about it from the reporter for Fortune.

Until mid November Dr. Topol was also on the advisory board of a Canadian biotech firm called Forbes Medi-Tech Inc. that is also developing a cholesterol drug. Great Point was also an investor in that company. Dr. Topol was given stock options valued at $1 million in the company that would vest only if the drug was successful. The company's cholesterol lowering drug has proven to be unsuccessful so far.

A consortium of leading technical publishers announced a plan that would allow three patient advocacy groups to select hundreds of the latest journal articles, which would be made available on their Internet sites. The organizations are the American Cancer Society, American Diabetes Association and American Heart Association.

The publishers include the Elsevier unit of Reed Elsevier PLC, John Wiley & Sons, Blackwell Publishing. The consortium, called patientINFORM is expected to launch the project in the spring. The plan calls for the three organizations to have a free hand in selecting articles, making original text available to the public, along with interpretive text supplied by the three organizations.

NIH Director Elias Zerhouni has stated that all scientists working with NIH funding should make their work available on a free NIH Web site after a sic-month delay. Before announcing their final proposals in this area the NIH is still open to public comments as to anyone else's thoughts on the matter.

(12/9/04)-Eli Lilly and Co.'s clinical-trial drug Web site went on line today. The site, www.lillytrials.com initially is posting the test results for eight of its drugs. The drugs being followed are: Alimta; Cymbalta; Genzar; Prozac; Strattera; Symbax; Xigris and Zyprexia. The site is subdivided into 6 sections, which are as follows:

• Trial Results by Therapeutic Area;
• Trial Results by Product;
• Initiated Trials;
• Recruiting Trials;
• Terminology and
• Education.

The company said that more data will follow, and that it hopes to have information on all its products by mid-2005. According to Alan Breier, Lilly's chief medical officer, the site includes detailed scientific summaries of the tests written with physicians and scientists in mind. Doctors could benefit from reading the results to help make up their own minds as to the efficacy and safety of a particular drug. If the layman uses the site, he/she should consult with a medical professional before making any definitive determination about a particular drug.

(11/4/04)-The National Institute of Health has proposed that any scientist whose work is funded by NIH research-grant money should have the article published for free 6 months after the initial publication on a NIH public free Internet site. The reasoning behind this viewpoint is the belief that scientists, medical professionals and the public have the right to see this information, since public funds were involved in examining the matter. The NIH has asked for public comment until November 16.

Several publishers of medical journals oppose this free publication, since they feel that 6 months is too short a period before which the material becomes "public" knowledge. Subscriptions to medical journals can cost anywhere from $200 to $6,000 per year. NIH Director Elias Zerhouni defended the proposal saying that it is rare for a journal to have more than 30% to 40% of its content generated by NIH sponsored work.

There is an "open access" movement developing in the medical publishing field, with the Public Library of Science (PLoS) heading this movement. Dr. Harold Varmus, a former NIH director and Nobel laureate heads PLoS, which is a San Francisco, based non-profit organization. This group is being bankrolled by a $9 million gift from the Gordon and Betty Moore Foundation. The group published its first publication in 2003 under the title of PLoS Biology. Its second publication is PLoS Medicine.

Under "open access" publication, the publication charges the authors, who want dissemination of their work a fee of $1,500 instead of charging subscribers a fee. Under the NIH plan, after articles have been submitted and accepted for publication, an electronic version would be available on PubMedCentral, the U.S. Library of Medicine's free digital archive, which was formed in 2000.

(10/12/04) Democratic lawmakers have introduced a bill in Congress that would require makers of drugs and medical devices to register clinical trials of their products in a public database when they begin and report the results of the test as it progresses. The bill has the backing of the American Medical Association (AMA). The four Democratic senators who sponsored the billl are:Edward M. Kennedy of Mass.; Christopher J. Dodd of CT.; Tim Johnson of South Dakota and Ron Wyden of Oregon. The Democratic Representatives Edward J. Markey of Mass., and Henry A. Waxman of CA introduced a companion bill in the House.

The National Institute of Health (NIH) announced that it would seek a one year moratorium on private consulting arrangements between its scientists and pharmaceutical companies. The agency said it would need a year to develop the computer, training, oversight and auditing functions needed to ensure that such consulting arrangements would not lead to conflicts of interest.

The problem came into the public limelight in 2003 as a result of an investigation by the Los Angeles Times. An investigation by the Energy and Commerce Committee ensued. The investigation found that many scientists who were involved analyzing pharmaceuticals were in fact receiving payments from the same drug companies for whom they had consulting contracts.

Congressional investigators asked for a list from the NIH of scientists who had approved contracts with outside companies and how much they were being paid. The investigators also requested a list of the names of the consultants from 20 of the largest pharmaceutical companies. In cross checking the two lists, the investigators found that nearly 130 arrangements reported by the drug companies were apparently unknown to the NIH.

A group of leading medical journals released a plan to stop publishing the results of clinical trials unless a test is registered at its outset in a public database. The group calls itself the International Committee of Medical Journal Editors includes such high profile publications as The Journal of the American Medical Association, The New England Journal of Medicine, The Lancet and the Annals of Medicine. The group did not advocate the use of a particular register, but did say that the database currently run by the National Library of Medicine contained a template for the type of information they wanted. If a trial is not registered at its commencement, the committee said that its members would not publish the results of the trial.

Bills have been introduced in both Houses of Congress that would require drug trials involving human subjects to be registered in a public database before the trials would be allowed to proceed. Democratic members Representative Henry A. Waxman of California and Edward J. Markey of Massachusetts introduced the House version of the bill. A spokesman for the A.M.A , Dr. Ronald A. Davis, said that his organization would back legislation that would make the registration of a clinical trial a mandatory part of the trial's receiving approval by so-called institutional review boards(IRB). IRB is a group of specialists and officials at research institutes that must approve any clinical trial that involves human subjects.

PhRMA, the drug industry's trade group said it would launch an online database designed to include summary results of most of it's members studies, including those that were not published in medical journals. The database will be summaries and not the full data from the trial. Participation in the database will be voluntary by the members of PhRMA. It will contain data of the trials completed after October 1, 2002. The results of the trials will become public within a year of the trial's conclusion. The database will not involve registration of the trials as they get underway.

New York Attorney General Eliot Spitzer and the British drug company GlaxoSmithKline PLC agreed to settle a lawsuit over unpublished clinical trial data involving it antidepressant drug Paxil for $2.5 million. In addition to the monetary settlement the company agreed to publish summaries of all its company-sponsored clinical studies of drugs conducted after December 27, 2000.

Glaxo has now released the results of its clinical trials for its diabetes drug Avandia on its Web site, and according to Dr. Ronald L. Krall, a senior vice-president for world wide development for the company, the company will continue to post clinical trial results for all the companies studies done after December 27, 2000.

Each of the trials of the diabetes medication will show the purpose of the test, as well as it primary and secondary finding. Included in the group of drugs whose trial results will be posted on the site are Avodart, a treatment for benign prostate hyperplasia; Advair Diskus, an asthma medication and Valtrex, a drug for the treatment of herpes.

Each study summary will contain more than 20 categories of information, including efficacy, adverse side effects, whether the goals of the study were changed midstream, and whether the study was terminated early and why. "Our hope is that this will be a template for other companies," Mr. Spitzer stated.

Prescription drug labeling is another facet of the expanding debate over the incomplete disclosure and publication of the results of clinical drug trials. Labels are allowed to remain silent about the test results that the FDA turned down for one reason or another. Representative Henry A. Waxman, (Dem.-Ca.) sent a letter to Health and Human Services Secretary Tommy G. Thompson, urging him to release data from all pediatric drug trials that have been conducted under federal laws that encourage such tests.

Many health professionals have expressed concern that some drug labels omitted any reference to clinical drug trials that were negative or equivocal. Federal law bars the FDA from acknowledging that clinical tests were conducted, if the agency receives the test data as part of a drug company's effort to have an existing product approved for a new use or category of patients, and the FDA turns down the request. This is an especially worrisome issue when doctors are prescribing medication for off label usage.

Eli Lilly & Co. announced that it would publish on the company's Web site extensive data on almost all clinical drug trials, past and present, for drugs that it sells. Under the new policy, once a drug is on the market, it will publish data from all early to late-stage clinical trials, including safety information and outcomes.

Test results that did not support the hypothesis or that were contrary to the expected outcomes also will be included in the data that will be available for the public to view. The company expects to have the information on its Web site by the end of 2004. Lilly won't publish results of trials on drugs that aren't yet approved, but it will list on its Web site when late-stage trials are to begin. The company also promised to list all post marketing studies that explore using an approved drug for off-label purposes.

Merck & Co. has indicated it would support a government-run listing system. Johnson & Johnson has also indicated that it would support the idea of a clinical trial registry available for the public to view.

Three Democratic senators have sent letters to the FDA and the National Institute of Health in which they express an interest in setting up a national database for all clinical drug trials being conducted in the U.S. The three senators are: Senator Tim Johnson of South Dakota, Edward M. Kennedy of Massachusetts, and Christopher J. Dodd of Connecticut.

In the letter the senators asked what could be done to either improve the existing government-run database. They also expressed an interest in including all results of clinical trials by the drug companies. The existing database, which is called ClinicalTrial.gov is limited in that it is aimed at only helping people find out what clinical trials are being done in connection with certain life threatening diseases.

Officials of the World Health Organization also said that they were working on a plan aimed at creating a worldwide database of drug trials.

The Medicines and Healthcare Products Regulatory Agency, which regulates Britain's drug industry, has requested information from the Danish pharmaceutical company H. Lundbeck AS for details as to why an unpublished negative study of an antidepressant it makes went unpublished. Researchers from Britain's National Collaborating Centre for Mental Health are examining the records in connection with the study which was performed on children using the drug citalopram, which is sold in Europe under the brand name Cipramil by Lundbeck.

The drug is sold in the U.S. by Forest Laboratories Inc. under the brand name of Celexa. It is expected that the records of Forest Labs will also be examined in connection with this matter. Celexia is the fourth most common antidepressant prescribed for children one to 17 in the U.S.in 2002, the last year for which the records are available. Although the drug was not specifically approved for usage on children, once it has been approved, doctors are free to use it for off-label purposes.

The American Medical Association has adopted a resolution that urges the federal government to create a database in which all clinical drug trials in this country would be listed at their outset. The AMA said it was taking this initiative because the positive results that are often announced are frequently biased by the drug company that sponsors the trial. On the other hand negative or adverse reaction results are very frequently overlooked and not even announced to the public.

This announcement from the AMA comes on top of a decision by the Committee of Medical Journal Editors to consider the publication only of clinical trials that have been registered from the start. Some of the leading medical journals are part of this group including The Journal of the American Medical Association, The New England Journal of Medicine, The Lancelet and The Annals of Internal Medicine. In the U.S. drug companies consider the data proprietary, and the FDA is forbidden by law to make the data public without the drug companies consent.

In England a pharmaceutical trade group, the Association of the British Pharmaceutical Industry has recommended that its members voluntarily create a trial registry. So far 8 of the 80 members of the group have created such a directory for their drug trials. One of the most comprehensive sources for clinical-trial data is the Cochrane Collaboration, which is a British based nonprofit group. Volunteers search the world's medical literature to find randomized clinical trials. Their site is located at www.trials-central.org

As part of the policy, the AMA requested that the institutional review boards, or IRBs, require registering in the proposed database as a condition for allowing a clinical trial to proceed. IRBs are charged with monitoring the treatment of participants in clinical trials.

Subsequently GlaxoSmithKline PLC announced that it would set up a database of the results of all tests run on a drug before its approval for marketing as well as subsequent tests of that same medication. That information would be listed after a drug has been approved or after any subsequent tests were completed. Merck & Co. announced that it also supports the idea of a government-run database that would keep track of all late-stage clinical drugs trials from start to finish. It would include a list of drug trials for medications approved since 2000. 

Pharmaceutical companies are always in the market to create potentially "new" drugs that lead to additions to its "portfolio" of drugs and hopefully become a "blockbuster" drug in its pursuit of financial gain. The process to reach the stage of FDA approval is a long and hazardous one, in many ways similar to investing in IPOs on the stock market. It starts by a drug company looking at its "stock" of drugs and having its medical chemists seek new structures for the drug that could have potentially clinically useful results. Once the drug is constituted chemically, it is assayed for its mechanism of action in the company's lab and may be tested on animal models of the disease to be targeted. The drug needs to show good absorption, distribution, metabolism and excretion properties to move down the pike to the end result of consumer demand.

If all goes well, it is then unveiled before the professional research community at seminars, such as the spring meeting of the American Chemical Society (ACS), in symposia usually entitled "First Time Disclosure of Clinical Candidates". It is here where medical chemists learn about the structure and pharmacological properties of new therapeutic drugs.

Interestingly, as far as we can determine, there is no regulatory requirement for a drug company to make a public announcement of a new agent's structure or its entry into drug trials. Companies guard their secrets from their competitors, to get a head start to the goal of acceptance by the FDA. This is a not uncommon practice in most corporations and it would seem unfair to condemn.

To further protect themselves, drug companies file patent applications where the information is buried among reams of patents that are harder to abstract the information from, than the tasks given to Hercules. They also disclose it to regulatory agencies in a confidential package reminding one of the "need to know" classifications associated with national security at its highest level. Good corporate practices!

Like a good chess player, first time disclosures by researchers at the ACS meeting are very purposeful at many different levels. The researcher is interested in communicating to the scientific community the best results, to peak interest in a drug's progress, to attract potential venture partners and to stimulate stock movement if the company is a publicly listed stock. After all, this is not an eleemosynary adventure. Public relations contribute to sales.

Press releases are picked-up by the media who may hype a drug without further ado, or suggest that it is the magic bullet in development. Stock can soar on such an announcement. This announcement can attract venture capitalists to help pay for development of the drug..

Below are two examples of drugs in the works may explain the process in a practical way.

Warfarin is a primary anticoagulant used to prevent strokes as result of atrial fibrillation, a not uncommon condition in the elderly characterized by irregular contractions of cardia atria, that can cause clot induced strokes. Warfarin is a very difficult drug to administer because of its adverse reaction profile, resulting in a large number of fibrillation patients not receiving this therapy. There appears to be a large market for this type of drug. This has lead medical chemists to develop a new drug that could inhibit clot formation (thrombin inhibitors) and would involve once-a-day oral administration. They began looking for small molecule inhibitors of thrombin and the other enzymes involved in the blood coagulation process and could have a long half-life when ingested.

By developing a template for thrombin inhibitors and its activity, researchers at Merck Research Laboratories, West Point, PA identified chemical sites on thrombin associated with breakdown of its function. By developing a way to prevent or block such breakdown while maintaining the elements critical for clot inhibition, they would have a potentially effective drug. It was an attempt to optimize drugs function. Merck has developed two such compounds that are now in Phase I clinical trials.

Another drug introduced at the last ASC seminar in the spring of 2003 was palindore, a schizophrenia medication. Wyeth Research, Princeton NJ, is developing this drug. It is described as a low-activity agonist of D2 and D3 dopamine receptors perceived as strong role players in schizophrenia development. What they want to target with this drug is the "negative symptoms" of the disease as opposed to the drugs on the market that treat primarily "positive symptoms" a swell as reduce or eliminate the serious neurological side effects. It would be similar to some of the atypical antipsychotics already on the market but have less adverse effects. Palindore is thus constructed to have a high affinity for D2 and D3 receptors, act as a partial agonist, and has showed promise in animal models used to identify antipsychotic agents. Clinical trials have now begun for this drug.

It may be many years, (or they may be withdrawn), before these research drugs reach the level of clinical use.

Many of the research-based pharmaceutical companies are facing an uncertain outlook. Revenues for these manufacturers are threatened by the fact that their top selling drugs have recently lost patent protection or will do so in the near future. At the same time, the flow of new molecules from the research pipeline is dwindling. For the year 2001, the FDA approved only 28 completely new drugs. One study reported that the research productivity in the pharmaceutical industry dropped 25% from the first to second half of the 1990's.

Pharmaceutical firms are adopting different drug development approaches including finding new formulations and alternative ways of administering existing drugs or developing "me-too" drugs (drugs similar to ones on the market) with more favorable side effect profiles. The later results in marginal improvement over existing drugs, with the patent system allowing the drug manufacturers to safeguard the length of the drug patent. It is the patent that allows the developer of the drug to get a return on the cost of development of the drug.

According to the Center for the Study of Drug Development at Tufts University, it takes on the average $802 million to bring a pharmaceutical product to market. The "first time disclosure" of the chemical entity associated with the development of the drug involves a minimal investment. Clinical development of the drug accounts for the major amount of the $802 million.

Robert Blackburn, Vice President and Chief Patent Counsel for Chiron Corporation stated at a symposium on health care and biomedical research: "The vast bulk of the $800 million average cost of bringing a drug to market is taken up with clinical development after the chemical entity has been invented. Yet the patent that the pharmaceutical company usually must rely on is for the chemical entity. Many thousands of patents are granted on chemical entities that could be developed, but only 1 in 10 proves suitable for development. And fewer than 1 in ten of those selected actually end up proving its worth and getting to market at the end of the day. This is why it costs $800 million". One could also add that this is the reason given for the high cost of new drugs.

Most drugs fail in development, just as the majority of start up businesses fail. Only with the failure of drugs, the glimmer of hope started at the "First Time Disclosure Seminars", amount to dashed hopes. Hope starts again with the next announcement of another chemical molecule development. Life goes on. Or so we hope. The cherry picking involved in these seminars need to be contained. Many announcements have an aura of dishonest salesmanship, inadvertently picked up and spread by the media in headlines touting the drugs "miraculous" actions.

See also
Clinical Drug Trials and Risks
Alzheimer's Disease-Clinical Trials-Part XX

FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE
" How to Select a Nursing Home"

Allan Rubin and Harold Rubin, MS, ABD, CRC, Guest Lecturer
updated September 19, 2016

http://www.therubins.com

e-mail: hrubin12@nyc,rr.com or allanrubin4@gmail.com

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