Rare Disease Advocacy: Treatment

On June 29 of this year, Lauren Erb, our Executive Director at the Caring for Carcinoid Foundation, will be speaking at a public hearing regarding rare diseases held by the FDA. The title of this hearing is “Considerations Regarding FDA Review and Regulation of Articles for the Treatment of Rare Diseases”. In honor of this occasion, I would like to continue the series of posts on Rare Disease Advocacy. The first part can be found here.

 One of the most obvious questions a person may be asked is why they chose to advocate for a particular issue/group. When this happens, it is very satisfying to have a clear set of reasons and facts to support your position. In an earlier post I discussed the difficulties many patients with a rare disease, including carcinoid cancer, face compared to other individuals with more common conditions. In this post, I would like to go over an important issue, one that is related to the public hearing being conducted by the FDA: treatments for rare diseases.

As almost everyone knows, the Patient Protection and Affordable Care Act was signed this year, resulting in major changes for the future of health care in the United States. Among the changes are provisions that seek to prevent insurance companies from placing lifetime caps (read about this issue here) and denying patients due to pre-existing conditions. There are very strong opinions surrounding this Act and rather than adding to that discussion, I will continue to focus on the issues rare disease patients face. Of course, both of the aforementioned changes will be beneficial to patients with rare diseases, but there are still steps that must be taken on their behalf.

Health insurance is very important for receiving health care in this country, but the type of care received will ultimately be determined by what is available. I believe it is fundamentally unfair that the availability of treatments is strongly determined by the prevalence of one’s condition, a fact that is out of any individual’s control, other things being equal. Put differently, if two people are similar in all respects, including income, behaviors, age, etc, except for the fact that Person A has a rare condition and Person B a common one of equal severity, I believe A has a legitimate complaint if no treatments are available for him while many exist for B. It may be argued that any given treatment for Person B’s condition will help more people, but I hope to show that this fact alone does not sufficiently explain the disparity between the availability of care options for common and rare diseases.

In this post, I will use the term ‘standard of care’, which should not necessarily be confused with its common use in law. As I use the term, it will simply mean the standard course of treatments used by physicians to treat a disease. Specifically, I will argue that patients with rare diseases like carcinoid cancer often lack a standard of care for reasons to be shown.

First and foremost, diseases have traits which researchers must learn about before treatments can be developed and a standard of care is established. Research is an essential part of this process. Without research it is difficult to know very basic things about a condition such as its natural progression, mechanisms, causes, etc. Yet research of this kind is seriously lacking for rare diseases. Very many resources are needed to do this kind of medical research and public interest is an important component in determining the types of conditions that scientists choose to study. For this reason, I strongly encourage you to support patients of these conditions and organizations like the Caring for Carcinoid Foundation that work diligently to provide funding and support in these areas.

The importance of research doesn’t end there. Without a standard of care established by research, it is difficult to know whether something a physician does is in fact helping the patient or if it is not making any difference at all. Even worse is the possibility that a physician unknowingly does something that harms the patient. Different people with the same condition will have a different progression of that condition. In research, the effectiveness of treatments is often measured by the difference in times to some endpoint or marker, for example simple survival or progression-free survival. A physician who sees two or three carcinoid patients cannot make any generalizable conclusions because even though there may be a difference in these times, it is almost impossible to know for certain whether that difference came from something he did without a sufficiently large sample size.

Combining these two aspects, research may also be able to show why a certain treatment is more effective in one person than another. Take the following real life example. In the paper found here Dr. Matthew Kulke describes a study done on the effects of Temozolimide. This study found that only a very small number of patients with carcinoid tumors responded to the drug, compared to a much higher proportion of pancreatic NET patients. Furthermore, response to the drug was strongly associated with deficiency of a specific enzyme (MGMT). 4 out of 5 patients with this deficiency responded to treatment with Temozolimide compared to 0 of 16 patients without this deficiency. Consider the implications of a study like this one. Without knowing the influence of this enzyme, a physician might prescribe Temozolimide to a large patient group with a small response rate, as opposed to a smaller patient group with a much greater response rate.

For obvious reasons, other things being equal, selling a product that many people want or need to buy will yield higher profits than selling one that only a few want or need. As a result, pharmaceutical companies will often most heavily invest in drug treatments marketable to the largest patient population. This is not the same as the issue of whether a drug treatment for a common condition will help more people than one for a rare condition. That fact may offer reasons to do more research for a more common condition, but I do not think it is sufficient to account for the extremely large gap that currently exists between the two. For example, consider that there are four major categories of drugs for the treatment of asthma: anti-Inflammatory drugs, Leukotriene blockers and Anti-Ige medications, (source) and a much greater number of approved drugs that fall into these categories. By comparison, Sandostatin is the only FDA approved drug for carcinoid tumors, and it is only approved to manage symptoms associated with the disease, and not intended as a cure or treatment for the disease itself.

 The lack of parity between rare and common diseases is prevalent in all stages of disease. Although the government has taken steps to improve this situation, for example passing the Orphan Drug Act in 1983 (offering incentives for pharmaceuticals to find treatments for rare conditions) the gap is still far too wide for comfort. Consider that the prevalence for all invasive cancer sites was roughly 11 million in the United States in 2006 (source) compared to about 25 million people with a rare disorder (source) . There is overlap between these two groups, but that figure should still be enough to convince you that more research and attention should be devoted to this issue. At the very least, I believe patients are entitled to receiving the benefit of a standard of care if not a cure. I hope you will join CFCF and other organizations in ensuring that everyone can receive treatment that has been shown to be effective and moving forward in the fight to end patient suffering.

Medical Research: Part 2

In this second part on medical and epidemiologic research, I'll be going over different types of studies that are conducted, why they're done, and how they're implemented. I will also consider certain concerns that may come about when conducting research.

The goal of research is reasonably straightforward, it is to gain knowledge with the hope that it is generalizable. In other words, the goal is to learn something based on a particular sample that can be applied to a much larger group. To do this, a researcher must first have a theory, [for example 'people who drink a lot of coffee get more headaches than people who don't'], devise an experiment to test that theory [find people, divide them into categories based on coffee consumption, and see which group gets more headaches], and then analyze the results [see if the difference in the groups was statistically significant and how big the difference was, aka the effect size].

If that description sounded much too simple, that is absolutely correct. There are many issues and considerations that go into conducting research, and I'm afraid I wouldn't be able to do it justice here. However, if you came in knowing little to nothing about research, I can hopefully give you enough of a grasp that you will be able to read a medical research paper and know what it is trying to say and how it came to those conclusions. To start off I'll describe some of the concerns one might have in conducting a study.

Confounding: From the first part of this series, it is easy to see that statistics has a great deal to do with associations. Confounding is a problem that leads to the appearance of a false causal relationship, because of a variable that is associated with both what the researcher is looking for [headaches] and where they are looking for it [people who drink a lot of coffee]. These are known as the dependant and independant variables. An example of a confounding variable for the given scenario may be lack of sleep. People who drink more coffee may be doing so because they get less sleep and lack of sleep may be leading to the headaches. What is important is that the lack of sleep has a relationship with both the independent and dependent variables. There are ways of controlling for confounding in the analysis, but if noone was looking for it, it might be assumed that the coffee itself was causing the headaches, when in fact it was the lack of sleep (this is a purely hypothetical example).

Bias: Unlike confounding, bias is a systematic error in the study that can't be corrected for in the analysis of the study. Examples include selection bias and misclassification bias. If, for example, people who drank a lot of coffee were much more likely to remember headaches than people who do not drink coffee, this misclassification regarding headaches would end up giving researchers results that underestimate the number of headaches in peope who don't drink coffee.

Types of research:

Randomized Controlled Trial: Often considered the gold standard, randomized controlled trials are often used to test some sort of intervention, such as medication. These types of trials are able to control many elements of the research and minimize both confounding and bias. How do they do this? When researchers want to test a difference of some factor, the ideal situation would be one in which two groups of completely identical people are compared while varying only the factor they were looking for. Obviously, this is impossible, but randomized controlled trials come about as close as possible. 'Randomized' means that the intervention is assigned randomly, this helps to eliminate selection bias by the researchers, and with a sample that is sufficiently large, will also result in two groups that are very similar. Very often, these types of trials are also blinded, meaning the individual does not know which group they are in. Trials can also be 'double blinded' so that the researchers conducting the study do not know either. The purpose of blinding is to prevent bias.

Observational research: Often, despite its usefulness, conducting a randomized controlled trial is not feasible. This is especially true of epidemiologic research. If you wanted to test the effects of smoking on some outcome, you wouldn't be able to 'assign' smoking to the participants in your study. Instead, you would have to gather a group of people, some of whom already smoke, and make observations about the results. The coffee example offered above would be an observational study because we did not assign coffee drinking to the participants.

*All of the above information is available in "Basic & Clinical Biostatistics" by Beth Dawson.

A couple of final points about statistics and research:  

• Don't overestimate the worth of a small p-value or be misled by the use of the term 'significant'. What statisticians mean when they say a difference is significant based on a small p-value (i.e. < .05) is that there is likely to be a difference, it does not say anything about what the difference is. In the population of coffee drinkers, 5 more may have headaches than the population of non-coffee drinkers, but there is a difference between this result being statisticaly significant, and pragmatically significant.
• Keep in mind that correlation does not imply causation, certain studies such as randomized controlled trials and cohort studes can be mindful of direction (whether the exposure came before the outcome), but other studies can't.
• Reading critically is a good way of spotting possible errors made by the researchers, including those of confounding and bias.

Some link for your consideration:


PubMed Home


Cohort and Case-Control Studies


Randomized Controlled Trials

Research: Part 1

In my previous posts, I’ve written a lot about the importance of being in charge of your own care making informed decisions. Fortunately, the amount of information available to anyone with access to a computer and internet is nothing short of astounding. Unfortunately, this plenitude can also be discouraging for people who are unsure of how to find what they need, or interpret it. With this post, I’ll try to go into some detail about finding and reading information about diseases and treatments, including a brief overview of studies and statistical methods.

Websites like WebMD are a great resource for general medical information and help. It offers an easy to use search engine and helpful tools for very many patients. Furthermore, people can be fairly confident about the content as all the information is reviewed by an independent board consisting of four physicians. Basic sites such as these, however, are not well suited for more in-depth and ‘cutting edge’ research, or even basic epidemiological studies. For these, it’s likely that you’re going to need to look at some research papers. This is particularly important for a rare disease like carcinoid, where very little is known about the disease and most of the new information is released through journal publications PubMed  is a very well organized database with articles related to medicine and biological sciences maintained by the United States National Library of Medicine at the National Institutes of Health. PubMed uses a specific system of organizing its content, partly due to the sheer number of articles. In order to search within PubMed effectively, knowing its MeSH vocabulary is invaluable. MeSH stands for Medical Subject Headings, and is used as a way to categorize all of the articles found within PubMed. A full overview would be difficult to do hear without the aid of visuals, but one can be found here: http://www.nlm.nih.gov/bsd/disted/video/. Pubmed will often have links to the full article, but even if they don't, should provide an abstract. Research and medical abstracts are a great way of getting a lot of information with a relatively small time investment, and shouldn't be taken for granted.

The importance of statistics is hard to underestimate in the modern scientific era. Because so much has to do with data, and statistics is the science of working with data, it is an integral part of almost all large scale endeavors. It is important to understand the advantages and disadvantages of working with information on a broad scale. In regards to things like medical interventions, it is invaluable to know the possible effect based on data from many individuals, and it is part of the reason that so called 'anecdotal evidence' is often viewed with such skepticism. Consider this in terms of simple games of chance, like that of flipping a coin. If a person were to hypothetically make all future assumptions about a coin based on three tosses, it is certain that they will be mistaken (because of the small and odd number of tosses). However, the more times a person flips a coin, the likelier it is that they will get a distribution of heads and tails that is closer to the 'true' probability of 1/2 for both. This is not dramatically out of line with what researchers attempt to do with clinical trials and observational studies, and it highlights the importance of having a large sample size. Testing a drug or trying to determine a risk factor for a certain condition is almost an entirely futile endeavor if done on a handful of individuals, particularly because unlike a coin toss, it is nearly always the case that there will be multiple factors in whether a person becomes sick with a certain condition, or recovers from one. Essentially, biostatistics is about taking what happens to a given group of people, and seeing what that means for a much larger group of people (referred to as the population).

At the same time, as important as it is to have a lot of data from many different sources, the more a statistical model says about a population, the less it may be able to say about an individual. Life, death, and disease are not a matter of coin flips, and it easy for people who know what the words 'median', 'mean', 'variance' and 'standard deviation'  mean to be confused about what those measures actually say. A great example of this was written about by Dr. Steven J. Gould after his diagnosis of peritoneal mesothelioma. Initially despondent at discovering that the median life expectancy among those with his condition was 8 months, he was quickly relieved to find that his specific status meant he would likely live much longer, which he indeed did. Go back to the example about coin tosses. Imagine hypothetically that the odds of getting tails was still 1 in 2 overall, but the individual odds depended on what color shirt (please ignore the fact that this makes no sense) the person flipping the coin happened to be wearing. For example, a person with a red shirt has a 1 in 4 chance of getting tails, whereas a person wearing blue would have a 3 in 4 chance. Taken together, and flipped a sufficient number of times, the mean outcome will still be around 1 in 2 for heads or tails, but this doesn't necessarily say much for someone wearing a red shirt! This is useful to keep in mind the next time you're reading a study or abstract about a large population, and specifically lead you to ask how similar the people in the study are to you, in ways that are relevant (hint: for better or worse, socioeconomic status is almost always relevant).

Finally, there is one additional caveat to think about when reading studies based on statistical models. While it may seem counter-intuitive, statisticians pose their questions around the null hypothesis, or the hypothesis that there is no difference. For example, for two groups of people, one of which takes aspirin and the other a placebo, the null hypothesis would be that there is no difference between the two groups regarding some outcome, such as headaches. Conducting a study is an attempt at rejecting the null hypothesis, and not necessarily about proving that aspirin cures headaches. Strictly speaking, a single statistical study very rarely serves to prove anything, it allows the possibility that the null hypothesis can be rejected with varying levels of certainty. There are many reasons for this, but go back one last time to the coin toss. Say the coin was tossed 10,000 times and it landed 4,998 times on heads, and 5,002 times on tails. If you think about it, it doesn't really make sense to say that this has proven anything definitive, but it does make sense to reject the idea that either tails or heads will land significantly more times than the other. Of course, for practical purposes, we treat matters differently, but this proverbial coin has two sides too. While we may take it that aspirin relieves headaches if there is enough of a difference between groups, statistically significant differences may have no actual practical implications.

Here are some basic terms and ideas you will likely come across when reading research papers:

Test statistics: Examples include t-value, chi squared, and Fisher's exact test. These are the numbers resulting from the various appropriate statistical tests used in a study. They are used to obtain the more practical numbers that follow.

p-value: The probability of obtaining a certain test statistic like the one obtained by the study (for example the t-value). Practically speaking, it is the probability of the observed difference (say less people taking aspirin getting headaches) happening as a result of chance. So the usual cutoff of .05 indicates that there is only a 5% chance that the differences observed by the study could have come about assuming the null hypothesis is true (or there is no difference).

Confidence intervals: These are paired with a confidence level, such as 95%, and together give a range of likely values given what was observed by the study. For example, say a study found that the mean weight of adult males with some condition is 165, and gives a 95% confidence interval of 154 to 190. This indicates that there is a 95% chance that the 'true' mean, reflecting the entire relevant population and not just those in the study, lies between 154 and 190.

1-tailed vs 2-tailed: This has to do with direction of a study. If the study is 1-tailed, this means that the researcher is essentially assuming that the deviation will occur in one direction (for example, a supplement will only cause someone to lose weight, and not gain it). Because of this assumption, the p-value of a 1 tailed study will be smaller than one from a 2 tailed study, which simply predicts that there will be some difference, without saying how it will be different. This means that 2-tailed tests are "stronger", and 1 tailed tests should only be used if there is good reason to believe that the difference will only be in one direction.

Risk ratio/relative risk/rate ratio and odds ratio: These are two different things, but the interpretation can be treated relatively equally (keeping in mind that the former is likely to be a stronger indication). RR and OR discuss the impact of some variable on an outcome, and can be expressed as follows: A relative risk of 4 indicates that group had 4 times the risk of an outcome than a different group. The number can also be less than 1, for example, group A had .31 times the risk.

*All of the above information is available in "Basic & Clinical Biostatistics" by Beth Dawson.

In the next part, I will go over different types of studies, and the possible advantages and disadvantages of each.

Some links for your consideration:

Dr, Gould's article about median life expectancy

Painless Guide to Statistics from Bates College

Just for fun: A counter-intuitive probability game called the Monty Hall Problem.

Rare Disease Advocacy- Diagnosis

Rare Disease Day is February 28th and it's a great opportunity to get involved and advocate for the countless number of people affected by these conditions. In the United States, a rare disease is one that occurs in less than 200,000 people, but there are estimated to be between 5,000 and 8,000 rare diseases in existence. In honor of this day, I will write a series of posts on the difficulty of having a rare disease, starting at the beginning.


It is easy to ask why we should care about rare diseases if they do in fact afflict a small number of people. This is in fact the unfortunate reality that many of these patients do in fact face, as evidenced by the problems they continue to be burdened by. As it can be noted from the numbers above, the total number of people with a rare disease is by no means small, NORD estimates the number in Americans to be nearly 30 million. There are a number of good reasons for considering them as a category in and of itself.


Patients with rare diseases face a more difficult time from the very start. I am referring to the diagnostic process. A great many patients are forced to wait a long time between the time that symptoms present themselves and the time they receive an official (and correct) diagnosis. This is if they ever receive a diagnosis at all. In order to illustrate why this is the case, it is necessary to take a look at the diagnostic process.


Many people believe that any given disease will always present a specific set of visible symptoms that will allow a doctor to easily identify and treat it. To understand why this is not so, I will use carcinoid as an example.


The majority of carcinoid patients are asymptomatic, and will not present any symptoms at all, even when they have metastasised. This implies a couple of things, but probably the most important is the fact that most people will continue to be diagnosed only accidentally.


The symptoms, known as carcinoid syndrome, occur in roughly 10% of carcinoids. These include include an increased chance of arthritis, heart disease, cramping, cyanosis (bluish skin spots), diarrhea, flushing, and wheezing.


Of these, the most diagnostically relevant is likely to be flushing. Flushing, however, has a multitude of causes. These include, but are by no means limited to: physical exertion, embarrassment, inflammation (which itself has many causes), caffiene consumption, rosacea, and high doses of niacin. The presence of flushing therefore, by itself does not indicate very much, something that is also true of the other symptoms.


There are multiple diagnostic tests to confirm the presence of carcinoid, but a biopsy, in which cells are removed and examined directly, is the only way to be sure. This is because tests typically either measure the effect a disease may have (akin to a 'non-visible symptom') or observe it through imaging techniques such as a PET scan, neither of which are infallible.


It becomes easy to see why diagnosing a rare disease is no easy matter. In order for a doctor to intentionally diagnose carcinoid, a patient must appear with a set of symptoms that indicate a specific disease enough to warrant ordering a test that may lead to a false positive or negative. The odds of a doctor suspecting a disease is almost certainly going to decrease with the prevalence of the disease. In the case of carcinoid, we can see a 10% chance of someone with a tumor presenting symptoms, and among those who see a doctor, a small likelihood that a doctor will see those specific symptoms as indicative of a rare disease and ordering an invasive procedure to confirm.


This is a serious issue, everything that follows diagnosis, including treatment methods, is obviously not an option if noone is aware of the disease in the first place. Fortunately, the situation is not hopeless. Part of advocacy is supporting research that not only includes finding a cure, but also discovering more about diseases and how to detect them early. The Caring for Carcinoid Foundation is steadfast in both, and they, and other organizations like them, require support.


It is my hope that people will recognize rare diseases as the serious problem that it is. Just as people cannot begin treating a disease until it is diagnosed, a problem as serious as this cannot begin to be corrected until it is fully acknowledged.


One way to offer this support is outlined by NORD. People around the country are asking their governors to issue a proclamation supporting Rare Disease Day. Check here to see if your state is included. If it isn't, I encourage you to contact your state's governor. Here is a sample template adapted from NORD:

DATE

Dear Governor:

We are writing to ask you to declare February 28, 2010, Rare Disease Day in [your state]. On that day, millions of people around the world will observe the 2^nd Annual Rare Disease Day to raise awareness of these diseases and the special challenges encountered by those affected.

In [your state], thousands of patients, their families, medical professionals, researchers, educators, social workers and others will join in this observance of Rare Disease Day. Rare diseases are those that affect fewer than 200,000 Americans, and there are nearly 7,000 such diseases affecting nearly 30 million Americans, according to the National Institutes of Health (NIH).

Rare Disease Day was observed for the first time in the United States last year and was a great success. This year, Rare Disease Day will be observed by millions of people throughout the U.S. and around the world. We respectfully ask you to consider designating the last day of February Rare Disease Day in [your state] on the basis that:

• Thousands of residents Wyoming are affected by rare diseases, as patients, friends and family, caregivers, physicians and other medical professionals, providers of social services, and researchers seeking to develop safe, effective treatments
• Many rare diseases are serious or even life-threatening
• Most rare diseases have no treatment
• About half of the people affected by rare diseases in the U.S. are children since many rare diseases are genetic
• Research on rare diseases is important because it often adds significantly to the general understanding of more common diseases

People with rare diseases experience certain challenges that occur as a result of the fact that their diseases are rare. These include:

• Difficulty in obtaining a timely, accurate diagnosis
• Limited treatment options
• Difficulty in finding physicians or treatment centers with needed expertise
• Treatments that are generally more expensive than those for common diseases
• Reimbursement issues related to private insurance, Medicare and Medicaid 
• A sense of isolation and hopelessness

Rare disorders affect the entire family of an individual patient. Caregivers endure ongoing stress and isolation managing the medical and financial issues that arise. When there is delay in the diagnosis of a rare genetic disorder, siblings may be born with the same condition. When a rare genetic disorder is diagnosed during adulthood, other family members may need to be informed that they may also be at risk…and this may lead to difficult decisions regarding genetic testing, if such testing is an option.

On the basis of all of the above, we hope you will join other governors around the nation in declaring February 28, 2010, Rare Disease Day in your state.

With best regards,

Your name

Your organization

There are also a number of activities and events taking place on February 28th, and they can be found on the Rare Disease Day website that will be linked at the end. Find your own way to support rare diseases, even if it only consists of mentioning it to a co-worker, friend or family member. While it may not seem like much, every new person made aware of the problems posed by rare diseases is another step towards finding a solution. To me, there's something poetic about small groups of individuals banding together to fight against a collection of rare diseases that together pose a great threat.


Some links for your consideration:

Rare Disease Day website

The National Organization for Rare Disorders (NORD) website 

About.com Article on the difficulty of diagnosing rare diseases 

Doctor Patient Relationship

While you've probably thought about and discussed what your perfect husband or wife would be like, you probably haven't given as much thought to your perfect doctor. That's a shame, because when you think about it, your relationship with your (potential) spouse is pretty similar to the relationship you have with your doctor. Both are potentially long term partnerships where trust and open honest communication are absolutely necessary for the relationship to work. Both parties must be willing to really listen to the other. With chronic diseases such as carcinoid and related neuroendocrine tumors, the doctor-patient relationship becomes even more important than usual. As opposed to two brief visits a year, most such patients will come to see their doctor with increasing frequency, and also begin to rely on them for referrals to specialists and other services.

Much in the same way everyone's idea of their perfect spouse is different, people will likely disagree on what they want from their physician. This is convenient, because doctors come in a huge variety, and I don't simply mean their specialties. 'Bedside manner' is often the term used to describe the way doctors interact with their patients. The term itself seems a bit dated considering the drastic reduction in inpatient care, but that aside, people sometimes use bedside manner to mean anything the doctor does that doesn't have to do with actual medical care. I believe this is misleading because it seems to imply that there is a broad category of attributes that pertain strictly to the practice of medicine, and another broad category termed 'bedside manner' that deals solely with somewhat vague ideas like 'friendliness' or 'easy-going nature'. If you think back to the sections on Informed Consent, however, this notion makes less sense. The manner and effectiveness with which your doctor communicates with you is an essential part of medical care because it strongly influences how you make decisions regarding your own care. To illustrate this, I will use a very simplified example.

Think of an individual who is diagnosed with a rare cancer. There are two popular treatment options, the first giving a 15% chance of a total cure, 60% chance of no effect, and a 25% chance of exacerbating the condition. The second treatment option gives you no chance of full recovery, but will almost certainly manage your symptoms so you may live comfortably for many more years. Your doctor, fully aware of both of these options, prefers the possibility of a cure to the absence of one, and therefore recommends only the first option. Or maybe s/he mentions the second option briefly, and gives you a lot of cues that discourages you from considering it seriously. Whether or not you prefer option 1 or option 2 in this scenario shouldn't stop you from thinking that what the doctor did was wrong. Again, the decisions regarding your body should ultimately be seen as yours.

If you compound this hypothetical with the actual complexities of diagnoses and treatment options, it is easy to get a sense of how important the doctor-patient relationship is. I am not trying to portray the physician as a malicious practitioner bent on imposing his or her will on unsuspecting patients. However, it is important for your doctor to know what your values are beforehand, and equally important for you to trust that those values will mean something to your doctor. Often times, going through every single step is an impossibility. The better your doctor knows you, the easier it will be for him to give you information that will be truly relevant to you in making an informed decision.

Of course, non-medical attributes of doctors are important as well, the point I am attempting to make is that the medical and non-medical parts aren't always easy to distinguish. Most of us would like a doctor that is caring and empathetic, but all of us should insist that our doctors be informative and helpful. Whatever it is you want from your doctor, be honest and upfront about it (though certainly not rude), because as mentioned before, communication is key.


Some links for your consideration:

Caring for Carcinoid Foundation's very own Doctor Database. A comprehensive listing of doctors across specialties with a listing of patient references to help you make your own informed decision

US News article citing the Doctor-Patient relationship as the possible key to quality

Informed Consent Part Two: Sign Here Please

In this section about informed consent, I will cover two types of forms you may end up signing. The first is one is the consent form which you may be asked to sign by a hospital during your stay and the second is the form signed before undergoing clinical research. It is important not to confuse the two, in addition to knowing what it means for you when you do sign the form.

First and foremost, a consent form is just a piece of paper, and while pieces of paper tend to carry an almost mystical authority for many people, it should be known that these forms in particular are not necessarily binding in many important respects. In most cases, forms are a way for the hospital or physician to show that information exchange took place, and the patient subsequently consented to the procedure. This gives all the more reason to make sure you have the information detailed in the first part of this series prior to signing anything when at all possible.

For consent forms themselves to have any power, they must still follow the guidelines mentioned before. The more general the information and authorization a form is, the less relevant it is. For example, signing a blanket consent form that authorizes the hospital to perform any and all procedures on your body is next to useless. Your signature does not mean that the standard of informed consent outlined by the courts no longer applies. Another thing to keep in mind is that a consent form is not a binding contract, meaning you can back out of a procedure even after you’ve signed the form. This is generally discouraged, and patients should very carefully consider their choices prior to consenting to a medical procedure, but it is still your legal right to refuse treatment at any point that it is possible to do so (it’s probably too late if you are already on the operating table and under sedation). People have a right to deny treatment, even when doing so will result in their death.

Informed Consent Forms for Research

The reason that consent forms are different for clinical research is that they are required by Federal regulations, and therefore must include certain information. The same principles apply in research as they did with any other medical procedures, and once again they are based on patient autonomy. Autonomy rests on the basic notion that persons should be treated with respect, which includes considering them capable of making decisions that impact them. If you don’t believe this, then I’ll go ahead and make the decision for you and say you should.

Medical research is obviously very important, but a large share of responsibility is left to the individual participants to safeguard their own interests against those of the researchers. One of the requirements for research to be conducted is something called clinical equipoise. This concept means that there is both sufficient reason to believe that the intervention will not induce harm, balanced by sufficient lack of evidence that there is a great benefit. After all, if you know for a fact that something will attain a certain goal, research would be unnecessary. For this reason, be sure to understand, at minimum, the intent, likely outcome, and risks of any trial or experimental procedure you undergo. This involves reading the informed consent form carefully, and discussing anything that is unclear to you with the researcher. Taken directly from “The Rights of Patients”, here is a list of things you should find and understand on a consent form when participating in research.

• A statement that the study involves research, an explanation of its purposes and the expected duration of the subject's participation, and a description of the procedures to be followed, identifying which are experimental;
• A description of reasonably forseeable risks or discomforts to the subject;
• A description of any reasonably expected benefits to the subject or to others;
• A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;
• A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
• For research involving more than minimal risk, an explanation about any compensation or medical treatments available if injury occurs;
• An explanation of whom to contact for answers to questions about the research and research subject's rights, and whom to contact in the event of a research-related injury;
• A statement that participation is voluntary and that refusal to participate will involve no penalty or loss of benefits; and that the subject may discontinue at any time without penalty or loss of benefits to which the subject is otherwise entitled.1

And again, here are some external sources for your consideration.

Example of a hospital consent form (note how broad it is)

Example of a research consent form

Guide to Informed Consent from the National Cancer Institute.

1. Annas,George, "The Rights of Patients" p209-210

Lifetime Insurance Caps

The Caring for Carcinoid Foundation encourages all carcinoid and related neuroendocrine tumor patients to join NORD (National Organization of Rare Disorders) in its fight to end lifetime insurance caps as soon as possible. Many patients must seek out costly therapeutic alternatives in order to receive the best care available. Furthermore, this issue is particularly relevant to patients with carcinoid and related neuroendocrine tumors as they may require chronic care and high-cost drug therapies. Therefore, CFCF supports NORD in rejecting lifetime insurance caps in insurance markets.

What is a lifetime insurance cap?

A lifetime insurance cap is a method used by health insurance companies to limit the total amount that will be paid out. In that way they are similar to deductibles and co-payments, except instead of asking for money out-of-pocket from insurers, they are limiting, or setting a cap, on the amount that people with health insurance will receive for their health care. As the name implies, this cap on payouts is for the entire life of the individual who is insured, the only way to get a reset is to find a new insurance plan. Finding a new insurance plan can become difficult to impossible in many instances where that insurance cap has been used up.

Why does this matter for me?

This is an issue that should matter to everyone for a number of reasons. First, rising health care costs means that fixed caps become increasingly inappropriate. From 2000 to 2008, national health care expenditures increased by 13.6% (HUS 2008), and they are projected to continue rising at high rates. A million dollar payout at the beginning of that period is therefore worth less (gets you less care) than the same amount in 2008, and increasingly less in the future.

This is a particularly critical issue for patients with rare and/or chronic diseases like carcinoid and NETs, which anybody can fall victim to. This matters because diseases that are rare and/or chronic tend to be more expensive. Rarity drives up costs because effective treatment methods such as pharmaceuticals and technologies have not been developed to the same degree as more common diseases, and what treatments there are tend to cost more. There are a number of contributing factors to this, including the necessary incentive structure for enticing drug companies to develop treatments.

Chronic conditions, especially those without a cure, cost more than acute conditions for more obvious reasons. The continuous need for care builds up and becomes very expensive over time. A 2 million dollar cap could quickly disappear in the span of a few surgeries. With a condition such as carcinoid that is both rare and chronic, it is easy for patients to burn through the lifetime cap, leaving them with no insurance to cover their necessary continuing care.

Carcinoid is a disease that is both rare and chronic, and therefore people with this condition should be particularly concerned about lifetime caps and how to reform them.

Here is some information on carcinoid and NETs:

While the age adjusted incidence (number of new cases over a given time) for neuroendocrine tumors has increased from 1973 to 2004, the estimated 29-year limited duration prevalence (number of people alive with a disease diagnosed within the last 29 years) as of January 1, 2004 was 103,312 in the United States, making carcinoid and NETs a rare condition. Data is from research done by Dr. James Yao in “One Hundred Years After “Carcinoid”: Epidemiology of and Prognostic Factors for Neuroendocrine Tumors in 35,825 Cases in the United States”.

As a result, the comparatively fewer available therapies and surgeries tend to be more expensive, for reasons previously mentioned. This increase does not include non-medical costs. An example of this may be a person who does not have anyone in close proximity that is capable of giving the best, or even decent level of care because of the rarity of their disease. As a result, they may be forced to travel great distances just to receive care, and be burdened with all the associated costs of doing so.

Finally, carcinoid, like many cancers, is chronic and deadly. There is currently no cure for carcinoid, meaning that there is no specific time period when treatment will no longer be necessary. This means that even if costs of treatment weren’t already high, the considerable time frame for treatment alone could easily leave someone with a low lifetime insurance cap with no resources after a few years.

What can I do?

Many groups are currently fighting to reform the current lifetime caps on insurance plans. The National Organization for Rare Diseases (NORD) is advocating the elimination of lifetime caps by supporting a letter being circulated by Rep. Patrick Kennedy. Your support would be tremendously helpful. I have included contact information for Representatives and Senators, in addition to a template provided by NORD, we at CFCF encourage you to call or e-mail them soon.

Call the switchboard at (202) 224-3121 and ask to be transferred to your local representative.

Find House e-mail addresses here: http://www.house.gov/

Find Senator e-mail addresses here: http://www.senate.gov/

Here is the template, feel free to modify and personalize it in any way that suits you.

Good morning/afternoon. My name is _____________________ and I am a constituent living in (city, state). I have a rare disease.

I am calling to bring to your attention a letter that Rep. Patrick Kennedy is circulating in Congress. This letter calls for the immediate abolition of lifetime insurance caps in the House health care reform bill, HR 3200.

As this bill is currently written, patients may have to wait up to nine years after reform is enacted to see those lifetime caps eliminated. People like me who have rare diseases face possible financial ruin if lifetime insurance caps are not immediately abolished. This issue is very important to me.

Will Representative (insert name of your Representative) sign on to Patrick Kennedy's letter?