Pharma Marketing

Do not join the Dallas Buyers Club. Expanded Access explained.

Dallas Buyers Club is a powerful movie. Based on true story of Ron Woodroof it shows how patient has to fight the system instead of receiving a treatment for the deadly disease. Everything seems to ally against suffering patient. Health Care Professionals driven by greed offer inefficient therapy under strict clinical trial regime. FDA officers are enforcing cruel regulations confiscating “illegal” but life-saving medications. Even the judge from liberal California, although compassionate is forceless. Dallas Buyers Club is a coalition of suffering people turned into outlaws for trying to save their lives.
Is pharmaceutical industry and its regulators really so cruel? Why Woodroof and his club were persecuted instead of receiving help? Is it possible that such story happens today with some other disease?

Clinical Trials – Why Ron could not get AZT in the proper dose in the hospital.

At the moment depicted in the Dallas Buyers Club, AZT (zidovudine, also known as azidothymidine, trade name Retrovir) in the U.S. was in the clinical research, probably in Phase III of the process.

English: AZT (zidovudine), the first medicatio...
English: AZT (zidovudine), the first medication shown to be effective against HIV. From the National Institutes of Health website. (Photo credit: Wikipedia)

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Phases of Clinical Research


  • Phase 0:  The first in-human research of new drug is called an exploratory investigational new-drug study or phase 0 study. It is done before traditional phase I trials. Smaller than therapeutic doses of a new drug are given to a small group of patients (typically fewer than 15) for roughly a week to determine pharmacodynamic and pharmacokinetic properties.
  • Phase I: Researchers test a new drug or treatment in a small group of healthy volunteers for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
  • Phase II: The drug or treatment is given to a larger group (about 100 -300) of people who have the disease or condition that the product potentially could treat. In this phase researchers see if the medicine is effective and are able to further evaluate its safety.
  • Phase III: The drug or treatment is given to large groups (1000 to 3000) of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
  • Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug’s effect in various populations and any side effects associated with long-term use.

Phase 2 and Phase 3 clinical trials generally involve a “control” standard. It means that some of the participants do not get tested substance, but inactive placebo or other, existing treatment if available. To avoid any bias, there is a special process to randomly decide who gets a tested substance, called randomization. At this point no one knows if the new therapy is efficient or maybe dangerous, so getting placebo is not necessarily worse option. Additional process to avoid bias in the results of the research is called blinding. Single-blinding means, that patients do not know whether they are treated with tested substance. Even better procedure, double-blinding means that also the research team does not know who receives what. Patient is informed about the substance s/he receives only at the specified time of the study, when it cannot impact the results.
Due to this procedures, it is not possible for patient to decide a dosage or even to be sure that the specific drug is given. In the story of Dallas Buyers Club, Ramona starred by Jared Leto could not be sure that her medicine is AZT and not just placebo.
Clinical studies are necessary to identify adequate dosage and eliminate risks that could overwhelm benefits of new therapy. There is always limited number of participating patients with specific conditions, so it takes long time to gather representative sample and see the results of the study. The whole process takes years to be completed, but it is needed to approve new drug to be available on the market.  

Expanded access – Would it be possible to import medicine for Ron legally?

AIDS patients could not wait for clinical trials, this is why Dallas Buyers Club and other similar communities existed. In that time, there was no easy, legal way to provide access to the treatment for patients in need. This experience affected current regulations in the U.S., and now there is a number of ways that allow access to the investigational or non-approved therapies for serious or life-threatening conditions, including but not limited to HIV/AIDS. Additionally, there is a way to expedite process of approval for the treatment in so-called FDA fast track drug development program.

Access to Investigational Drugs Outside of a Clinical Trial (expanded access)

Expanded access, sometimes called “compassionate use,” is the use of an investigational drug outside of a clinical trial to treat a patient with a serious or immediately life-threatening disease or condition who has no comparable or satisfactory alternative treatment options.
FDA regulations allow access to investigational drugs for treatment purposes on a case-by-case basis for:

  • individual patients, including in emergencies

  • intermediate-size patient populations

  • larger populations under a treatment protocol or treatment investigational new drug application (IND)


To permit treatment of a patient with an investigational drug under an expanded access program, FDA requests following conditions to be met:


  • The patient’s disease or condition has no satisfactory approved therapy. An example of this is a rare type of cancer that has no known or approved treatment. Or, it may be the case that the available treatments did not work for the patient.

  • The potential benefit for the patient justifies the potential risks. An example of this is the potential for longer survival with a disease or condition.

  • The expanded availability of the untested drug will not interfere with that product’s development. For example, access to an investigational drug should not interfere with enrollment in clinical trials needed to demonstrate the drug’s safety and effectiveness.


Additionally, the drug manufacturer and the patient’s doctor must make special arrangements to obtain the drug for the patient. These arrangements must be authorized by the FDA. These safeguards are in place to avoid exposing patients to unnecessary risks.

Just as in clinical trials, these investigational drugs have not yet been approved by the FDA as safe and effective. They may be effective in the treatment of a condition, or they may not. They also may have unexpected serious side effects. It is important for you to consider the possible risks if you are interested in seeking access to an investigational drug.
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How to Get Expanded Access to an Investigational Drug?

The process must begin with your healthcare provider, who should follow these steps:

  • Your healthcare provider must contact the company that manufactures the drug to make sure it is willing to provide the drug.

  • Your healthcare provider must submit an Investigational New Drug (IND) [link to section below] application to the appropriate FDA review division.

  • In an emergency situation, the request to use the drug may be made via telephone or other rapid means of communication, and authorization to ship and use the drug may be given by the FDA official over the telephone. With emergency INDs, shipment of and treatment with the drug may begin prior to FDA’s receipt of the written IND submission that is to follow the initial request.

  • In a non emergency situation, the IND must be received by FDA before shipment of and treatment with the drug may begin. These non emergency requests are known as individual patient INDs.


The IND Application

The IND application is required to gain access to an investigational drug outside a clinical trial. The application should include the following information:

  1. Statement that this is a request for an individual patient IND for treatment use (specifying whether it is an emergency IND or individual patient IND), which should be included at the top of the correspondence and on the mailing cover.

  2. Brief clinical history of the patient including:

    • Diagnosis

    • Disease status

    • Prior therapy

    • Response to prior therapy

    • Rationale for requesting the proposed treatment, including a list of available therapeutic options that would ordinarily be tried before the investigational drug, or an explanation of why use of the investigational drug is preferable to the use of available therapeutic options

    • Reference for a published protocol or journal article, if appropriate

  3. Proposed Treatment Plan including:

    • Dose (how much and how often)

    • Route of administration (by mouth, injection, etc.)

    • Planned duration (how long the product is to be taken)

    • Monitoring procedures

    • Modifications (e.g., dose reduction or treatment delay) for toxicity

  4. Chemistry, Manufacturing, and Controls Information and Pharmacology and Toxicology Information, including a description of the manufacturing facility. This can be done by providing a letter of authorization (LOA) that refers to this information if it has been previously submitted to FDA (for example, to an existing IND or new drug application). The treating physician should contact the sponsor of the previously submitted information for the authorization and letter. The LOA should include identifying information, such as the sponsor’s application (e.g., IND) number.

  5. Informed Consent Statement noting that informed consent and approval by an appropriate institutional review board (IRB) will be obtained prior to beginning treatment. In the case of an emergency, treatment may begin without prior IRB approval, provided the IRB is notified of the emergency treatment within 5 working days of treatment.

  6. Investigator Qualification Statement that specifies the training, experience, and licensure of the treating physician. The first two pages of a curriculum vitae typically contain this information and are usually sufficient.

  7. FDA Form 1571 completed with the treating physician listed as the sponsor. Download Form 1571 and view the instructions.

[Source: FDA]


Expedited approval

For the drugs that are the first available treatment or have advantages over existing treatments, the Food and Drug Administration has developed four distinct approaches to make such drugs available as rapidly as possible:

  • Priority Review

  • Accelerated Approval

  • Fast Track

  • Breakthrough Therapy


Priority Review

Prior to approval, each drug marketed in the United States must go through a detailed FDA review process. Since 1992, under the Prescription Drug User Act (PDUFA) a Priority Review designation is used to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. A Priority Review designation means FDA’s goal is to take action on an application within 6 months (compared to 10 months under standard review). Priority Review does not affect the length of the clinical trial period.

Accelerated Approval

It takes many years to fully assess whether a drug provides a real effect on how a patient survives, feels, or functions, and brings a clinical benefit. To make drugs for serious conditions that filled an unmet medical need approved earlier, FDA can use Accelerated Approval process and base its decision on a surrogate endpoint. A surrogate endpoint is a marker of therapeutic effect, that is thought to predict clinical benefit but does not measure it. Drug still needs to be evaluated after approval in Phase IV studies, and basing on the results of this Phase IV FDA can change its initial decision on approval (ie. withdraw one of labeled indication, or completely withdraw drug from the market if confirmatory tests do not prove enough clinical benefit).

Fast Track

Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

A drug that receives Fast Track designation is eligible for some or all of the following:


  • More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval

  • More frequent written correspondence from FDA about such things as the design of the proposed clinical trials and use of biomarkers

  • Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met

  • Rolling Review, which means that a drug company can submit completed sections of its Biological License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the application is completed before the entire application can be reviewed.  BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA


Breakthrough Therapy

Breakthrough therapy is the latest program at FDA that will complement the programs listed above. It facilitates and expedites drug development and review for serious conditions and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).

A drug that receives Breakthrough Therapy designation is eligible for the following:


  • All Fast Track designation features

  • Intensive guidance on an efficient drug development program, beginning as early as Phase 1

  • Organizational commitment involving senior managers


[Source: FDA]


British MHRA’s Early Access to Medicines

Early access to the innovative drugs is still a topic for regulators not only in the U.S. In the United Kingdom the latest development is an Early Access to Medicines program unveiled by the Government on 7th of March 2014. The program aims to accelerate access to innovative medicines for serious conditions, allowing doctors to prescribe the drugs after an initial scientific assessment by the Medicines and Healthcare Products Regulatory Agency (MHRA).
The program, funded by pharmaceutical companies, will be launched on April 2014. Suitable drugs  will receive a “promising innovative medicine” (PIM) designation. PIM designation will be  based on several years of clinical data assessed by MHRA, but before completion of Phase III trials. This will probably save several years in comparison to the standard process for approval, that will be run in parallel to the new program.
Early Access to Medicines is modeled after the FDA’s breakthrough therapy designation. British regulatory agency estimates that one or two therapies could be designated under the scheme each year. 
It seems there is no need for Dallas Buyers Club anymore.

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