43 replies to this topic

[jdog]

I've read anywhere from 100mg 1x daily, to 400mg 1x daily is a good dosage for Modafinil. I know people react differently to different things, so with that aside, what do you find to be the optimal dosage for you personally?

Also, are you able to get to sleep at night on that dosage?

[doug123]

Provigil (modafinil) does not seem to affect normal sleep patterns if taken as prescribed. However, that does not necessarily mean you can take Provigil before bedtime and expect to be able to sleep...Modafinil is only FDA approved to treat narcolepsy, sleep apnea, and SWSD. However, it is commonly prescribed off-label.

The complete prescribing information is attached as a .pdf. It is only current as of 2004.

Attached Files

•  prescribing_info.pdf   69.59KB   41 downloads

[jdog]

Ok, I understand that's the perscribing information, but what I'm interested in people's subjective optimal dosages, frequency, etc.

[doug123]

Sorry, I didn't really reply directly to your post as much as I did the topic name. You might consider starting a poll, or searching? Take care.

[jdog]

Perhaps my question is irrelevant since the documentation info you provided states that there hasn't been any evidence of an increase in benifit past a dosage of 200mg. I guess I was just wondering about dosages in the higher range.

[garethnelsonuk]

Personally I take 200mg in the morning to wake up properly and another 200mg at midday if needed. Up to 600mg in a day is the highest safe dose.

[doug123]

Perhaps my question is irrelevant since the documentation info you provided states that there hasn't been any evidence of an increase in benifit past a dosage of 200mg. I guess I was just wondering about dosages in the higher range.

Yeah, well -- that prescribing information was published back in 2004.

Here is some new evidence that might suggest it's neuroprotective:

Neurosci Lett. 1999 Nov 19;275(3):215-8.

A stereological study on the neuroprotective actions of acute modafinil treatment on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigral lesions of the male black mouse.

Aguirre JA, Cintra A, Hillion J, Narvaez JA, Jansson A, Antonelli T, Ferraro L, Rambert FA, Fuxe K.

Department of Physiology, School of Medicine, Malaga, Spain.

The effect of an acute administration of the vigilance-promoting drug modafinil ((+/-)(diphenyl-methyl)-sulfinyl-2 acetamide; Modiodal) on the nigrostriatal dopamine system was studied after damage induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) by means of immunohistochemistry for tyrosine hydroxylase (TH) and a stereological method. MPTP (40 mg/kg) reduced from 24,380 +/- 902 to 13,501 +/- 522 and from 37,868 +/- 3300 to 20,568 +/- 1270, respectively, the number of TH immunoreactive (IR) and non-TH IR nigral neurons. Co-administration of Modafinil restored to normal the number of these neuronal populations. MPTP treatment induced also a reduction in the volume of TH IR neurons, which was counteracted by Modafinil administration. The data provide morphological evidence, based on unbiased stereological analysis, for a potential neuroprotective role of Modafinil, not only in dopaminergic neurons, but also with a similar magnitude in the non-DA nerve cell population of the substantia nigra after MPTP lesion.  These results suggest that Modafinil has a neuroprotective role in the substantia nigra via a still undefined mechanism in which a crucial role of DA uptake blockade should be excluded. Modafinil may therefore have a therapeutic potential in neurodegenerative processes such as those occurring in Parkinson's disease.
PMID: 10580713 [PubMed - indexed for MEDLINE]

Expert Opin Pharmacother. 2006 May;7(7):837-48.

Neuroprotective agents in schizophrenia and affective disorders.

Krebs M, Leopold K, Hinzpeter A, Schaefer M.

Department of Psychiatry and Psychotherapy, Charite-Universitatsmedizin Berlin, Campus Charite Mitte, Schumannstr. 20/21, D-10117 Berlin, Germany. Michael.Krebs@charite.de

With the exception of dementia, the use of neuroprotective agents in psychiatric disorders is not yet well established. However, recent data from brain imaging studies and clinical trials support the view that neurodegenerative mechanisms may play a role in the pathophysiology of schizophrenia and affective disorders. Further evidence for the use of neuroprotective agents can be drawn from the findings that second-generation antipsychotics, mood stabilizers and antidepressants have been shown to have neuroprotective effects in vitro and in vivo. Neuroprotective agents as add-on therapies (e.g., modafinil, erythropoietin, glycine, D-serine, memantine and celecoxib) are currently being evaluated in schizophrenia and related disorders. This paper reviews the current options for neuroprotective treatment approaches focusing on schizophrenia and affective disorders.PMID: 16634707 [PubMed - in process]

Acta Pharmacol Sin. 2004 Mar;25(3):301-5.

Neuroprotective mechanism of modafinil on Parkinson disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Xiao YL, Fu JM, Dong Z, Yang JQ, Zeng FX, Zhu LX, He BC.

Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China. fjmin@21cn.com

AIM: To observe the neuroprotective mechanism of modafinil on Parkinson disease (PD) models induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). METHODS: The model of PD was induced by intraperitoneally injecting MPTP into C57BL/6J mice for 4 d. Modafinil (i.p., 50 or 100 mg/kg(-1)/d(-1)) was administered at 30 min following MPTP for 4 d and for another 10 d continuously. The contents of dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA), glutamine (Glu) in the striatum, and the contents of GABA, Glu, malondialdehyde (MDA), and glutathione (GSH) in the substantia nigra (SN) of model mice were determined. RESULTS: Modafinil (50 and 100 mg/kg) prevented against the decrease of the contents of DA, 5-HT, and NA in the striatum and GSH, GABA in the SN induced by MPTP, but reduced the increase of MDA in the SN and GABA in the striatum induced by MPTP. Modafinil preferentially inhibited striatal GABA release, but it did not change the increase of nigrostriatal Glu release induced by MPTP. CONCLUSION: The anti-oxidation and the modulation of nigrostriatal GABA and striatal NA and 5-HT release contributed to the neuroprotective effects of modafinil on PD induced by MPTP.
PMID: 15000882 [PubMed - indexed for MEDLINE]

Behav Pharmacol. 2006 Sep;17(5-6):453-62.
Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects.

van Vliet SA, Vanwersch RA, Jongsma MJ, van der Gugten J, Olivier B, Philippens IH.
aDepartment of Diagnosis and Therapy, TNO Defence, Security and Safety, Rijswijk bDepartment of Psychopharmacology, Utrecht Institute of Pharmaceutical Sciences and Rudolf Magnus Institute of Neurosciences, Utrecht University, Utrecht, The Netherlands.

The vigilance-enhancing agent modafinil has neuroprotective properties: it prevents striatal ischemic injury, nigrostriatal pathway deterioration after partial transsection and intoxication with 1-methyl-1,2,3,6-tetrahydropyridine. The present study determines the protective effects of modafinil in the marmoset 1-methyl-1,2,3,6-tetrahydropyridine Parkinson model on behavior and on monoamine levels. Twelve marmoset monkeys were treated with a total dose of 6 mg/kg 1-methyl-1,2,3,6-tetrahydropyridine. Simultaneously, six animals received a daily oral dose of modafinil (100 mg/kg) and six animals received vehicle for 27 days. Behavior was observed daily and the locomotor activity, hand-eye coordination, small fast movements, anxiety-related behavior and startle response of the animals were tested twice a week for 3 weeks. Modafinil largely prevented the 1-methyl-1,2,3,6-tetrahydropyridine-induced change in observed behavior, locomotor activity, hand-eye coordination and small fast movements, whereas the vehicle could not prevent the devastating effects of 1-methyl-1,2,3,6-tetrahydropyridine. Dopamine levels in the striatum of the vehicle+1-methyl-1,2,3,6-tetrahydropyridine-treated animals were reduced to 5% of control levels, whereas the dopamine levels of the modafinil+1-methyl-1,2,3,6-tetrahydropyridine-treated animals were reduced to 41% of control levels. The present data suggest that modafinil prevents decrease of movement-related behavior and dopamine levels after 1-methyl-1,2,3,6-tetrahydropyridine intoxication and can be an efficaceous pharmacological intervention in the treatment of Parkinson's disease.

PMID: 16940766 [PubMed - in process]

[paul]

I am a modafinil user and would be interested to as to long term affects but I think at the moment it is very hard to tell.
I take a daily dose of 200 mg, everyone is different. The dose at which it works on you is the best dose to take and you will notice it, its not to say that if you need twice as much you are potentially putting yourself at twice a high risk of toxicity, it’s probably due to your body being more efficient at getting rid of it. As for whether this drug is neuroprotective there is no real way of telling from any of the published articles. The ones quoted above are based on a compound called MPTP, well known in heroin addicts of California in 1982 who got sold a duff batch which later showed to contain this nasty chemical which totally destroyed dopamine cells in their striatal cells causing irreversible Parkinson’s like symptoms on all these poor young fellars. Advice firstly, don’t buy dodgy drugs! From the reports above it seems highly likely that modafinil effects the dopaminergic system. I say this because MPTP depleted killed off these guys dopamine cells by being taken up by a specific dopamine transporter (DAT) and wrecking the mitochondria inside (the powerhouse of the cell). This to me suggests that modafinil has had these protective effects by being a similar shaped molecule to this compound competing it out and getting and preventing its affects (this is my guess, I have not had access to the journal so it could be wrong).
So if modafinil is acting in a similar way to dopamine what does this mean in terms of adverse long term affects. As mentioned depletion of dopamine is the cause behind Parkinson’s disease ie rigidity. I notice with myself that I am more active whilst taking it, concurring with the expected opposite to parkinsons like symptoms. On the other hand excess dopamine is thought to be the cause behind schizophrenia, indeed most antipsychotic drugs block dopamine. This does not mean that buy taking it long term you are likely to develop it since it is mainly caused buy genetics. Merely this suggests that some of the reasons why dopamine causes schizophrenia may also affect a modafinil user, enhanced sensory responses and vigllance. Dopamine is a modulator and can enhance any active stimulus going through your brain.
I feel I am willing to take the risk by taking this drug, it improves my life and there may well turn out to be positive benefits long term but equally negative affects can not be rulled out. I trust the FDA, they license it at the moment for long term use in a couple of conditions so they can not be too wooried about it.

[garcia2002]

I've read anywhere from 100mg 1x daily, to 400mg 1x daily is a good dosage for Modafinil. I know people react differently to different things, so with that aside, what do you find to be the optimal dosage for you personally?

Also, are you able to get to sleep at night on that dosage?

I think it depends on what you are using it for. I'm female 5'7" and weigh 140. I work outside the home and use it to keep away 2-4 pm and 7-9 pm sleepies. I drag my butt out of bed at 5:30 or 6 a.m. and titrate with coffee until 11 or 12, then I take 50 mg and zoom through my afternoon until 4 or 5 pm and take another 25 mg and am super mom/wife until about 10:30 or 11. If I need to pull an all-nighter before a family trip, the holidays, work emergencies etc.. I do that with ease on 75 mg every 8 hours. I have no problems sleeping and on odd occasions have taken 25 mg just before bed in order to wake up with ease in about 5 hours.

[impulsive]

Im 6'2" 180 pounds, Male


100MG/day is fine

I did, 500MG on the first day, then continued with 100mg

The provigil will kick in within an hour or two, and the 'full on' effects last like 8 hours, but it's possible to maintain it for up to 40 hours with relative ease. This drug turned my brain into a sponge, what happens to you as a result of that, depends on what that sponge is exposed to. If you have a decent amount of willpower, you should be fine.

[jdog]

I am a modafinil user and would be interested to as to long term affects but I think at the moment it is very hard to tell.
I take a daily dose of 200 mg, everyone is different. The dose at which it works on you is the best dose to take and you will notice it, its not to say that if you need twice as much you are potentially putting yourself at twice a high risk of toxicity, it’s probably due to your body being more efficient at getting rid of it. As for whether this drug is neuroprotective there is no real way of telling from any of the published articles. The ones quoted above are based on a compound called MPTP, well known in heroin addicts of California in 1982 who got sold a duff batch which later showed to contain this nasty chemical which totally destroyed dopamine cells in their striatal cells causing irreversible Parkinson’s like symptoms on all these poor young fellars. Advice firstly, don’t buy dodgy drugs! From the reports above it seems highly likely that modafinil effects the dopaminergic system. I say this because MPTP depleted killed off these guys dopamine cells by being taken up by a specific dopamine transporter (DAT) and wrecking the mitochondria inside (the powerhouse of the cell). This to me suggests that modafinil has had these protective effects by being a similar shaped molecule to this compound competing it out and getting and preventing its affects (this is my guess, I have not had access to the journal so it could be wrong).
So if modafinil is acting in a similar way to dopamine what does this mean in terms of adverse long term affects. As mentioned depletion of dopamine is the cause behind Parkinson’s disease ie rigidity. I notice with myself that I am more active whilst taking it, concurring with the expected opposite to parkinsons like symptoms. On the other hand excess dopamine is thought to be the cause behind schizophrenia, indeed most antipsychotic drugs block dopamine. This does not mean that buy taking it long term you are likely to develop it since it is mainly caused buy genetics. Merely this suggests that some of the reasons why dopamine causes schizophrenia may also affect a modafinil user, enhanced sensory responses and vigllance. Dopamine is a modulator and can enhance any active stimulus going through your brain.
I feel I am willing to take the risk by taking this drug, it improves my life and there may well turn out to be positive benefits long term but equally negative affects can not be rulled out. I trust the FDA, they license it at the moment for long term use in a couple of conditions so they can not be too wooried about it.

If you happen to come accross any new studies about long-term side-effects from modafinil make sure you post it.

A little off topic here, but you trust the FDA? Wish I could say the same. I don't think they make all their decisions in the American people's best interests.

Life Extension Magazine has an article about some of their questionable decisions

http://www.lef.org/m...pearson2_1.html


I mean, why would you promote cheap and natural dietary supplements (i.e. folic acid) to prevent disease before it occurs - not at all lucrative - when you can make all the money you ever dreamed of by just treating health problems after they occur; thanks to your friends in the multi-billion dollar drug industry?

[jdog]

Im 6'2" 180 pounds, Male


100MG/day is fine

I did, 500MG on the first day, then continued with 100mg

The provigil will kick in within an hour or two, and the 'full on' effects last like 8 hours, but it's possible to maintain it for up to 40 hours with relative ease. This drug turned my brain into a sponge, what happens to you as a result of that, depends on what that sponge is exposed to. If you have a decent amount of willpower, you should be fine.

Do you know if there's a huge crash if you stay awake for say, 40 hours?

What about when you do go to bed? Do you need extra hours of sleep in order for your body to recouperate after staying awake that long?

Also, is the quality of sleep better, worse, or the same when taking modafinil?

By the way, I definitely agree with you about your brain turning into a sponge. [lol]

[jubai]

I have a newfound love for low-dose Modafinil, as I'm trying to reduce the stimulating effect and possible longterm negatives.

I use Piracetam and Alpha-gpc cyclicaly, and found Modafinil to be potentially too stimulating with them, and 200mg taken alone is still too much.

30mg to get used to it, then 50mg a day combined with medium-dose Piracetam and Rhodiola has a nice synergestic effect, all 3 promote energy but low-dose Modafinil gives a calm focus unlike the hyper feeling of stimulants, and the "chill effect" of Rhodiola mellows out residual excessive spikes.

[doug123]

Life Extension Magazine has an article about some of their questionable decisions

http://www.lef.org/m...n2_1.html<br />


I mean, why would you promote cheap and natural dietary supplements (i.e. folic acid) to prevent disease before it occurs - not at all lucrative - when you can make all the money you ever dreamed of by just treating health problems after they occur; thanks to your friends in the multi-billion dollar drug industry?

I don't think the FDA are necessarily the real problem.

They might be easiest to point the finger at...

The facts are: the USFDA is a very small task force with a very limited budget that acts on laws passed through US legislation. All it would probably take to get the FDA to change its policies on allowing more preventative treatments and NIH funding on research on aging and cognition enhancement is a big enough lobby and pressure from elected officials' constituencies.

Consumer Reports (May 2004) and the “Dirty Dozen” unsafe herbs still readily available

· “CONSUMER REPORTS has identified a dozen (supplements) that … are too dangerous to be on the market. Yet they are.” Introductory paragraph in red ink.

· Factors contributing to unsafe supplements on the market.

· “ ‘The standards for demonstrating a supplement is hazardous are so high that it can take the FDA years to build a case,’ said Bruce Silverglade, legal director of the Center for Science in the Public Interest, a Washington D.C., consumer advocacy group”(pg. 12).

· “The FDA’s supplement division is understaffed and underfunded, with about 60 people and a budget of only 10 million “dollars)…” (pp. 12-13).

· “…Overwhelming opposition from Congress and industry forced it to back down” when the FDA first tried to regulate ephedra in 1997 (pg. 13).

· The public assumes a greater degree of government regulation than exists – in a 2002 Harris Poll of 1010 adults, 59% of respondents believed that supplements must be approved by a government agency before they can be sold to the public, 68% thought the government requires warning labels on supplements with regard to potential dangers, and 55% thought that supplement manufacturers could not make safety claims without solid scientific support.

The FDA implements particularly high standards of evidence, as is discussed here.

Overview of Data and Eligibility for a Qualified Health Claim

A health claim characterizes the relationship between a substance and a disease or health-related condition (21 CFR 101.14(a)(1)).  The substance must be associated with a disease or health-related condition for which the general U.S. population, or an identified U.S. population subgroup is at risk (21 CFR 101.14(b)(1)).  Health claims characterize the relationship between the substance and a reduction in risk of contracting a particular disease.[2]  In a review of a qualified health claim, the agency first identifies the substance and disease or health-related condition that is the subject of the proposed claim and the population to which the claim is targeted.[3]  FDA considers the data and information provided in the petition, in addition to other written data and information available to the agency, to determine whether the data and information could support a relationship between the substance and the disease or health-related condition.[4] 

The agency then separates individual reports of human studies from other types of data and information.  FDA focuses its review on reports of human intervention and observational studies.[5] 

In addition to individual reports of human studies, the agency also considers other types of data and information in its review, such as meta-analyses,[6] review articles,[7] and animal and in vitro studies.  These other types of data and information may be useful to assist the agency in understanding the scientific issues about the substance, the disease or health-related condition, or both, but can not by themselves support a health claim relationship.  Reports that discuss a number of different studies, such as meta-analyses and review articles, do not provide sufficient information on the individual studies reviewed for FDA to determine critical elements such as the study population characteristics and the composition of the products used.  Similarly, the lack of detailed information on studies summarized in review articles and meta-analyses prevents FDA from determining whether the studies are flawed in critical elements such as design, conduct of studies, and data analysis.  FDA must be able to review the critical elements of a study to determine whether any scientific conclusions can be drawn from it.  Therefore, FDA uses meta-analyses, review articles, and similar publications[8] to identify reports of additional studies that may be useful to the health claim review and as background about the substance-disease relationship.  If additional studies are identified, the agency evaluates them individually.

FDA uses animal and in vitro studies as background information regarding mechanisms of action that might be involved in any relationship between the substance and the disease.  The physiology of animals is different than that of humans.  In vitro studies are conducted in an artificial environment and cannot account for a multitude of normal physiological processes such as digestion, absorption, distribution, and metabolism that affect how humans respond to the consumption of foods and dietary substances (Institute of Medicine, National Academies of Science, 2005).  Animal and in vitro studies can be used to generate hypotheses or to explore a mechanism of action but cannot adequately support a relationship between the substance and the disease.

FDA evaluates the individual reports of human studies to determine whether any scientific conclusions can be drawn from each study.  The absence of critical factors such as a control group or a statistical analysis means that scientific conclusions cannot be drawn from the study (Spilker et al., 1991, Federal Judicial Center, 2000).  Studies from which FDA cannot draw any scientific conclusions do not support the health claim relationship, and these are eliminated from further review.

Because health claims involve reducing the risk of a disease in people who do not already have the disease that is the subject of the claim, FDA considers evidence from studies in individuals diagnosed with the disease that is the subject of the health claim only if it is scientifically appropriate to extrapolate to individuals who do not have the disease.  That is, the available scientific evidence must demonstrate that: (1) the mechanism(s) for the mitigation or treatment effects measured in the diseased populations are the same as the mechanism(s) for risk reduction effects in non-diseased populations; and (2) the substance affects these mechanisms in the same way in both diseased people and healthy people.  If such evidence is not available, the agency cannot draw any scientific conclusions from studies that use diseased subjects to evaluate the substance-disease relationship.

Next, FDA rates the remaining human intervention and observational studies for methodological quality.  This quality rating is based on several criteria related to study design (e.g., use of a placebo control versus a non-placebo controlled group), data collection (e.g., type of dietary assessment method), the quality of the statistical analysis, the type of outcome measured (e.g., disease incidence versus validated surrogate endpoint), and study population characteristics other than relevance to the U.S. population (e.g., selection bias and whether  important  information about the study subjects--e.g., age, smoker vs. non-smoker was gathered and reported).  For example, if the scientific study adequately addressed all or most of the above criteria, it would receive a high methodological quality rating.  Moderate or low quality ratings would be given based on the extent of the deficiencies or uncertainties in the quality criteria.  Studies that are so deficient that scientific conclusions cannot be drawn from them cannot be used to support the health claim relationship, and these are eliminated from further review.

Finally, FDA evaluates the results of the remaining studies.  The agency then rates the strength of the total body of publicly available evidence.[9]  The agency conducts this rating evaluation by considering the study type (e.g., intervention, prospective cohort, case-control, cross-sectional), study category , the methodological quality rating previously assigned, the quantity of evidence (number of the various types of studies and sample sizes), whether the body of scientific evidence supports a health claim relationship for  the U.S. population or target subgroup, whether study results supporting the proposed claim have been replicated[10], and the overall consistency[11] of the total body of evidence.[12]  Based on the totality of the scientific evidence, FDA determines whether such evidence is credible to support the substance/disease relationship, and, if so, determines the ranking that reflects the level of comfort among qualified scientists that such a relationship is scientifically valid.

Thank you Opales for finding the link from which I quoted data above.

Also, I don't necessarily believe everything (or anything?) I read...and I tend to take an even closer look at evidence when it is presented by companies and/or individuals who have a conflict of interest in selling substances they advocate the use of. I myself have engaged in sales of products that I advocated the use of; and unfortunately the payoff for selling products for which there is no peer reviewed evidence to support their purported uses was quite low; not to mention risky! You can read more about the role of conflict of interest in medicine by clicking here. The reason why the individual I referenced was charged criminally was due to the fact that he did not seem to disclose a conflict of interest. Many companies and individuals (some highly accredited, such as Dr. Sinclair) do seem to have a conflict of interest in some of their research...however, when a researcher openly discloses a conflict of interest, they disclose a potential bias and the individual(s) evaluating the data -- let's suppose the FDA in this case -- can prudently take that factor into account. The reason the individual in question was fined so heavily was due to the fact he was also an NIH researcher (therefore he solicits public funds -- i.e. -- US tax dollars):

CONFLICT OF INTEREST

Prudent stewardship of public funds that support research programs requires that appropriate steps be taken to ensure high quality results. Therefore, recipient organizations must establish safeguards to prevent employees, consultants, or members of governing bodies from using their positions for purposes that are, or give the appearance of being, motivated by a desire for private financial gain for themselves or others such as those with whom they have family, business, or other ties. Therefore, each institution receiving PHS funds must have written policy guidelines on conflict of interest and avoidance thereof. These guidelines should reflect state and local laws and must cover financial interests, gifts, gratuities and favors, nepotism, and other areas such as political participation and bribery. These rules must also indicate how outside activities, relationships, and financial interests are reviewed by the responsible and objective institution official(s).

In addition, the institution has the responsibility for maintaining objectivity in research by ensuring that the design, conduct, or reporting of research will not be biased by any conflicting financial interest of investigators responsible for the research in accord with the provisions of PHS regulations 42 CFR Part 50, Subpart F, and 45 CFR Part 94. (/grants/guide/notice-files/not95-179.html). See also (http://grants.nih.go...licy/coifaq.htm) for frequently asked questions about research investigator financial conflict of interest and Part II of the NIH Grants Policy Statement (http://grants.nih.go...tm#_Toc54600065). For information on the workshop on conflict of interest, held on the NIH campus on September 30, 2002, see the Conflict of Interest Workshop Summary (MS Word or PDF).

Institutions which identify research investigator financial conflicts of interest are required to report the conflicts to the NIH Grants Management Officer (GMO) at the NIH Institute or Center (I/C) which funds or will fund the project. Questions should be directed to I/C GMO's at the address shown on NIH notices of grant awards.

Edited by nootropikamil, 09 January 2007 - 04:28 AM.

[sentinel]

Modafinil/modalert etc actions and reactions tend to mirror your reaction to Caffeine or other CNS stimulants ie if you are caffeine sensitive then you are probably going to be sensitive to the effects of Modafinil too. This is worth knowing before you embark on your first dose as I, for example, am highly stimulant sensitive and 200 MG (recommended dose on accompanying documentation) was too much for me and if I had taken as much as the appropriately named "Impulsive" (500MG! GZus) I think my heart would have jumped out of my chest [:o]

Unlike other nootropics (if you class Modafinil as a nootropic) you get immediate effects/feedback from modafinil, so you lose very little time by starting relatively low (eg 50mg twice a day) then working the dose up until you feel it. I take 100mg in the morning and 100 mg early afternoon if I need it (after 6:00pm it impacts my sleep as it has a relatively long half-life).

Also, other then the "wakefulness" factor, different people vary in their response eg high levels of focus or even blinkered over-focus, where people get too wrapped up in a single task or focal point, making it difficult to multi task or keep an eye on what is going on around them. Modafinil definitely "works" and has tangible effects for everyone but that doesn't mean everyone is going to need or like it.

Sentinel

[jdog]

Life Extension Magazine has an article about some of their questionable decisions

http://www.lef.org/m...n2_1.html<br />


I mean, why would you promote cheap and natural dietary supplements (i.e. folic acid) to prevent disease before it occurs - not at all lucrative - when you can make all the money you ever dreamed of by just treating health problems after they occur; thanks to your friends in the multi-billion dollar drug industry?

I don't think the FDA are necessarily the real problem.

They might be easiest to point the finger at...

The facts are: the USFDA is a very small task force with a very limited budget that acts on laws passed through US legislation. All it would probably take to get the FDA to change its policies on allowing more preventative treatments and NIH funding on research on aging and cognition enhancement is a big enough lobby and pressure from elected officials' constituencies.

Consumer Reports (May 2004) and the “Dirty Dozen” unsafe herbs still readily available

· “CONSUMER REPORTS has identified a dozen (supplements) that … are too dangerous to be on the market. Yet they are.” Introductory paragraph in red ink.

· Factors contributing to unsafe supplements on the market.

· “ ‘The standards for demonstrating a supplement is hazardous are so high that it can take the FDA years to build a case,’ said Bruce Silverglade, legal director of the Center for Science in the Public Interest, a Washington D.C., consumer advocacy group”(pg. 12).

· “The FDA’s supplement division is understaffed and underfunded, with about 60 people and a budget of only 10 million “dollars)…” (pp. 12-13).

· “…Overwhelming opposition from Congress and industry forced it to back down” when the FDA first tried to regulate ephedra in 1997 (pg. 13).

· The public assumes a greater degree of government regulation than exists – in a 2002 Harris Poll of 1010 adults, 59% of respondents believed that supplements must be approved by a government agency before they can be sold to the public, 68% thought the government requires warning labels on supplements with regard to potential dangers, and 55% thought that supplement manufacturers could not make safety claims without solid scientific support.

The FDA implements particularly high standards of evidence, as is discussed here.

Overview of Data and Eligibility for a Qualified Health Claim

A health claim characterizes the relationship between a substance and a disease or health-related condition (21 CFR 101.14(a)(1)).  The substance must be associated with a disease or health-related condition for which the general U.S. population, or an identified U.S. population subgroup is at risk (21 CFR 101.14(b)(1)).  Health claims characterize the relationship between the substance and a reduction in risk of contracting a particular disease.[2]  In a review of a qualified health claim, the agency first identifies the substance and disease or health-related condition that is the subject of the proposed claim and the population to which the claim is targeted.[3]  FDA considers the data and information provided in the petition, in addition to other written data and information available to the agency, to determine whether the data and information could support a relationship between the substance and the disease or health-related condition.[4] 

The agency then separates individual reports of human studies from other types of data and information.  FDA focuses its review on reports of human intervention and observational studies.[5] 

In addition to individual reports of human studies, the agency also considers other types of data and information in its review, such as meta-analyses,[6] review articles,[7] and animal and in vitro studies.  These other types of data and information may be useful to assist the agency in understanding the scientific issues about the substance, the disease or health-related condition, or both, but can not by themselves support a health claim relationship.  Reports that discuss a number of different studies, such as meta-analyses and review articles, do not provide sufficient information on the individual studies reviewed for FDA to determine critical elements such as the study population characteristics and the composition of the products used.  Similarly, the lack of detailed information on studies summarized in review articles and meta-analyses prevents FDA from determining whether the studies are flawed in critical elements such as design, conduct of studies, and data analysis.  FDA must be able to review the critical elements of a study to determine whether any scientific conclusions can be drawn from it.  Therefore, FDA uses meta-analyses, review articles, and similar publications[8] to identify reports of additional studies that may be useful to the health claim review and as background about the substance-disease relationship.  If additional studies are identified, the agency evaluates them individually.

FDA uses animal and in vitro studies as background information regarding mechanisms of action that might be involved in any relationship between the substance and the disease.  The physiology of animals is different than that of humans.  In vitro studies are conducted in an artificial environment and cannot account for a multitude of normal physiological processes such as digestion, absorption, distribution, and metabolism that affect how humans respond to the consumption of foods and dietary substances (Institute of Medicine, National Academies of Science, 2005).  Animal and in vitro studies can be used to generate hypotheses or to explore a mechanism of action but cannot adequately support a relationship between the substance and the disease.

FDA evaluates the individual reports of human studies to determine whether any scientific conclusions can be drawn from each study.  The absence of critical factors such as a control group or a statistical analysis means that scientific conclusions cannot be drawn from the study (Spilker et al., 1991, Federal Judicial Center, 2000).  Studies from which FDA cannot draw any scientific conclusions do not support the health claim relationship, and these are eliminated from further review.

Because health claims involve reducing the risk of a disease in people who do not already have the disease that is the subject of the claim, FDA considers evidence from studies in individuals diagnosed with the disease that is the subject of the health claim only if it is scientifically appropriate to extrapolate to individuals who do not have the disease.  That is, the available scientific evidence must demonstrate that: (1) the mechanism(s) for the mitigation or treatment effects measured in the diseased populations are the same as the mechanism(s) for risk reduction effects in non-diseased populations; and (2) the substance affects these mechanisms in the same way in both diseased people and healthy people.  If such evidence is not available, the agency cannot draw any scientific conclusions from studies that use diseased subjects to evaluate the substance-disease relationship.

Next, FDA rates the remaining human intervention and observational studies for methodological quality.  This quality rating is based on several criteria related to study design (e.g., use of a placebo control versus a non-placebo controlled group), data collection (e.g., type of dietary assessment method), the quality of the statistical analysis, the type of outcome measured (e.g., disease incidence versus validated surrogate endpoint), and study population characteristics other than relevance to the U.S. population (e.g., selection bias and whether  important  information about the study subjects--e.g., age, smoker vs. non-smoker was gathered and reported).  For example, if the scientific study adequately addressed all or most of the above criteria, it would receive a high methodological quality rating.  Moderate or low quality ratings would be given based on the extent of the deficiencies or uncertainties in the quality criteria.  Studies that are so deficient that scientific conclusions cannot be drawn from them cannot be used to support the health claim relationship, and these are eliminated from further review.

Finally, FDA evaluates the results of the remaining studies.  The agency then rates the strength of the total body of publicly available evidence.[9]  The agency conducts this rating evaluation by considering the study type (e.g., intervention, prospective cohort, case-control, cross-sectional), study category , the methodological quality rating previously assigned, the quantity of evidence (number of the various types of studies and sample sizes), whether the body of scientific evidence supports a health claim relationship for  the U.S. population or target subgroup, whether study results supporting the proposed claim have been replicated[10], and the overall consistency[11] of the total body of evidence.[12]  Based on the totality of the scientific evidence, FDA determines whether such evidence is credible to support the substance/disease relationship, and, if so, determines the ranking that reflects the level of comfort among qualified scientists that such a relationship is scientifically valid.

Thank you Opales for finding the link from which I quoted data above.

Also, I don't necessarily believe everything (or anything?) I read...and I tend to take an even closer look at evidence when it is presented by companies and/or individuals who have a conflict of interest in selling substances they advocate the use of. I myself have engaged in sales of products that I advocated the use of; and unfortunately the payoff for selling products for which there is no peer reviewed evidence to support their purported uses was quite low; not to mention risky! You can read more about the role of conflict of interest in medicine by clicking here. The reason why the individual I referenced was charged criminally was due to the fact that he did not seem to disclose a conflict of interest. Many companies and individuals (some highly accredited, such as Dr. Sinclair) do seem to have a conflict of interest in some of their research...however, when a researcher openly discloses a conflict of interest, they disclose a potential bias and the individual(s) evaluating the data -- let's suppose the FDA in this case -- can prudently take that factor into account. The reason the individual in question was fined so heavily was due to the fact he was also an NIH researcher (therefore he solicits public funds -- i.e. -- US tax dollars):

CONFLICT OF INTEREST

Prudent stewardship of public funds that support research programs requires that appropriate steps be taken to ensure high quality results. Therefore, recipient organizations must establish safeguards to prevent employees, consultants, or members of governing bodies from using their positions for purposes that are, or give the appearance of being, motivated by a desire for private financial gain for themselves or others such as those with whom they have family, business, or other ties. Therefore, each institution receiving PHS funds must have written policy guidelines on conflict of interest and avoidance thereof. These guidelines should reflect state and local laws and must cover financial interests, gifts, gratuities and favors, nepotism, and other areas such as political participation and bribery. These rules must also indicate how outside activities, relationships, and financial interests are reviewed by the responsible and objective institution official(s).

In addition, the institution has the responsibility for maintaining objectivity in research by ensuring that the design, conduct, or reporting of research will not be biased by any conflicting financial interest of investigators responsible for the research in accord with the provisions of PHS regulations 42 CFR Part 50, Subpart F, and 45 CFR Part 94. (/grants/guide/notice-files/not95-179.html). See also (http://grants.nih.go...licy/coifaq.htm) for frequently asked questions about research investigator financial conflict of interest and Part II of the NIH Grants Policy Statement (http://grants.nih.go...tm#_Toc54600065). For information on the workshop on conflict of interest, held on the NIH campus on September 30, 2002, see the Conflict of Interest Workshop Summary (MS Word or PDF).

Institutions which identify research investigator financial conflicts of interest are required to report the conflicts to the NIH Grants Management Officer (GMO) at the NIH Institute or Center (I/C) which funds or will fund the project. Questions should be directed to I/C GMO's at the address shown on NIH notices of grant awards.

I appreciate your comments, as they forced me to take a closer look at the details and reflect on the FDA. I forgot who this is quoted after, but a wise man once said something along the lines, that to never change one’s opinion is like standing water, and breeds demons of the mind. Anyhow, I'll take a look at this stuff and get back to you.

[REGIMEN]

IME 50mg 2-3X/day gives a nice undercurrent of focus and motivation. No need to feel like the horse is dragging you around when you can enjoy a nicely padded ride in the saddle. Apply that to the longterm, I suppose, and you've still got your britches (winkwink).

[impulsive]

Do you know if there's a huge crash if you stay awake for say, 40 hours?

What about when you do go to bed? Do you need extra hours of sleep in order for your body to recouperate after staying awake that long?

Also, is the quality of sleep better, worse, or the same when taking modafinil?

By the way, I definitely agree with you about your brain turning into a sponge.  [lol]

1) I dont know about a "crash" because I usually fall asleep around 11pm. 12am... Even on Modafinil id still lay down in bed at that time and go to sleep.

2) Same? Havent noticed a difference... I noticed a difference one night but, realized it was the Tyrosine that kept me up

[doug123]

CONFLICT OF INTEREST

Prudent stewardship of public funds that support research programs requires that appropriate steps be taken to ensure high quality results. Therefore, recipient organizations must establish safeguards to prevent employees, consultants, or members of governing bodies from using their positions for purposes that are, or give the appearance of being, motivated by a desire for private financial gain for themselves or others such as those with whom they have family, business, or other ties. Therefore, each institution receiving PHS funds must have written policy guidelines on conflict of interest and avoidance thereof. These guidelines should reflect state and local laws and must cover financial interests, gifts, gratuities and favors, nepotism, and other areas such as political participation and bribery. These rules must also indicate how outside activities, relationships, and financial interests are reviewed by the responsible and objective institution official(s).

In addition, the institution has the responsibility for maintaining objectivity in research by ensuring that the design, conduct, or reporting of research will not be biased by any conflicting financial interest of investigators responsible for the research in accord with the provisions of PHS regulations 42 CFR Part 50, Subpart F, and 45 CFR Part 94. (/grants/guide/notice-files/not95-179.html). See also (http://grants.nih.go...licy/coifaq.htm) for frequently asked questions about research investigator financial conflict of interest and Part II of the NIH Grants Policy Statement (http://grants.nih.go...tm#_Toc54600065). For information on the workshop on conflict of interest, held on the NIH campus on September 30, 2002, see the Conflict of Interest Workshop Summary (MS Word or PDF).

Institutions which identify research investigator financial conflicts of interest are required to report the conflicts to the NIH Grants Management Officer (GMO) at the NIH Institute or Center (I/C) which funds or will fund the project. Questions should be directed to I/C GMO's at the address shown on NIH notices of grant awards.

Not to go too far off topic...but to follow up on the conflict of interest/bias issues:

There is news published today that seems to infer that even third party funding on research can adversely affect the outcome. It seems this type of bias can be attributed to conflict of interest.

This same news seemed to be reported in several different sources, such as....

Time Magazine: Nutrition Studies Skewed by Industry Dollars?

From Time Magazine:

For anyone who tries to keep track of which foods provide which health benefits, life seemed a little more complicated this morning. The first major analysis of nutritional research found the science to be every bit as susceptible to sponsor bias as pharmaceuticals. In a paper published online Tuesday in  PloS Medicine researchers from Children's Hospital Boston report that when studies linking beverages to health are funded entirely by industry, the conclusions are four to eight times more likely to support the sponsor's commercial interest than studies with no industry funding. And the implications of the findings, says senior author David Ludwig, are far-reaching. "Whereas conflicts of interest in pharmaceuticals could affect the millions of people taking drugs," he says, "conflicts of interest in nutrition could affect everybody — because everybody eats."

The research analyzes 206 studies on the health effects of juice, milk, and soft drinks — all of them published over the five-year period ending Dec. 31, 2003, and archived in the National Library of Medicine's online database, Medline. Ludwig says his team focused on beverages because they provided a discreet, easily analyzed sample to test the hunch that nutritional science might be skewed by industry dollars. (More studies would be needed to assess the impact of sponsorship on food research, which the study did not address.)

Forbes: On Nutritious Drink Studies, Consider the Funding Source

"When a food company sponsors a study, it is much more likely to be positive" about the health effects of the product, said Dr. David Ludwig. He's the study's senior author and director of the Optimal Weight for Life program at Children's Hospital Boston, the pediatric teaching hospital for Harvard Medical School.

Ludwig and his colleagues analyzed 206 articles from medical journals that evaluated the health benefits or effects of soft drinks, juice and milk. The studies were published from 1999 to 2003.

Of the 206 studies, 111 supplied information on funding. To prevent bias in Ludwig's review, one researcher selected the articles for inclusion in the study. Another two researchers who were not told the funding sources classified each study as favorable, not favorable or neutral toward the beverage studied. A fourth researcher who didn't know the conclusions of the study determined the funding source and classified the studies, based on whether they would be beneficial, negative or neutral to the funder's bottom line.

Fox News: Industry Money May Bias Drink Studies

From Fox News:

"Everybody brings a point of view to the table, and in the long run, that's probably a good thing," Miller said.

But the authors say this point of view appears to influence results.

They used Medline, a compendium of scientific literature, to identify 538 studies about soda, milk or juice involving people, not animals. They targeted 206 that made a health claim directly related to the drink being studied _ for example, bone fractures related to calcium and milk intake, or immune system benefits from antioxidants in juice.

Of the 206 studies, only 111 gave information on funding: 22 percent were fully funded by industry and 32 percent got some industry money.

One group of reviewers analyzed study conclusions and classified them as favorable, neutral or unfavorable to the beverage in question. Another independent group of reviewers determined whether a study would help, harm or have no effect on the finances of the study sponsor.

MSNBC: Bias found in soft drinks research

From MSNBC:

Scientific research funded by the soft drinks industry is up to eight times more likely than independent studies to suggest that its products are healthy, according to the first detailed analysis of the topic released on Monday.

A study by doctors in Plos Medicine, an online medical journal, highlighted the potential for considerable bias in articles about soft drinks, fruit juices and milk in leading nutrition journals.

Of the 206 articles in serious academic journals it analysed, more than half of those who disclosed sponsorhip were fully or partly funded by the industry. Those that were industry-sponsored were between four and eight times more likely to draw favourable conclusions.

Scientific American reports:

News Source: Scientific American



January 08, 2007

Who paid for that study? Source affects outcome

By Maggie Fox, Health and Science Editor

WASHINGTON (Reuters) - One study shows that milk can help people lose weight. Another shows that tomato juice might prevent cancer and a third shows benefits to fizzy sodas.

But consumers should take those studies with a grain of salt, researchers reported on Monday. If a study was industry-funded, it was far more likely to have a positive finding than if it was paid for by the government or an independent group, the researchers found.

"We are not singling out any industry or any particular study," said lead researcher Dr. David Ludwig of Children's Hospital Boston and Harvard University.

"Our first look shows evidence strongly suggestive of bias," Ludwig said in a telephone interview.

The study, published by the Public Library of Science online journal PLoS Medicine, echoes other findings that show industry-funded research on drugs is more likely to be favorable to the drugs than independent research.

Ludwig's team reviewed 111 studies on soft drinks, juice and milk that were published between 1999 and 2003.

"We chose beverages because they represent an area of nutrition that's very controversial, that's relevant to children, and involves a part of the food industry that is highly profitable and where research findings could have direct financial implications," Ludwig said.

Studies funded entirely by industry were four times to eight times more likely to be favorable to the financial interests of the sponsors than those paid for by other groups, the researchers found.

Of the 22 studies clearly identified as funded by companies or industry groups, just three, or 13.6 percent, had findings that were unfavorable to the beverage studied.

More than 38 percent of the independently funded studies were negative, the researchers found.

This "raises serious concerns that some food industries may distort the scientific record on diet and health," Martijn Katan, professor of nutrition at Vrije Universiteit in Amsterdam, wrote in a commentary in the same journal.

Ludwig said the studies could be set up differently if they are funded by industry. Or it could be that sponsors choose not to publish studies that turn out unfavorable to their product, he said.

Researchers funded by industry may do rigorous work, but may choose to ask certain questions more likely to produce a result favorable to the product, Ludwig said.

"I don't blame researchers for this problem. I think that most are highly ethical and dedicated to science," Ludwig said.

He said the problem is that the government does not spend much money studying nutrition.

"Industry money becomes difficult to resist," he said. "Imagine ... you are facing the choice of accepting industry money or closing up shop."

Ludwig's study was paid for by his hospital and by the Charles H. Hood Foundation, a childhood health philanthropy.

Edited by nootropikamil, 09 January 2007 - 10:31 PM.

[impulsive]

no1 knows anything.... thats why you "dont" follow people

or, "learn from their mistakes"

everything in life is a risk...

Since this topic is about Modafinil; Modafinil helped me out a great deal.

Could it be bad for me? Yes
Is it possible it "didnt even do anything for me?" Yes

But, whenever I take it (study purposes), I can actually read & remember

thus making me feel better throughout the day

/end thread

[jdog]

no1 knows anything.... thats why you "dont" follow people

or, "learn from their mistakes"

everything in life is a risk...

To impulsive: Wise man once say, "A stupid man dosen't learn from his mistakes. A smart man learns from his mistakes. A wise man learns from others mistakes."



Now, to Adam: After reading your posts, it's not clear to me whether your arguments are against my belief that the FDA has made questionable decisions in the past, or if you're just contesting the LEF article. If it is the latter, then by all means, you've certainly driven home the point in that conflicting interests can and do occur, but that's all you've shown - a correlation does not imply causation.

Now, if your following arguements are in response to my original comment regarding questionable decisions made by the FDA, I sense a nice straw-man fallacy.

Please allow me to retort:

I don't think the FDA are necessarily the real problem.
They might be easiest to point the finger at...

So, just because someone or something might be the easiest to “point the finger” at, does that mean it shouldn’t be done?

The facts are: the USFDA is a very small task force with a very limited budget that acts on laws passed through US legislation.

I'm assuming when you say "the USFDA," you're implying the organization as a whole. I haven't seen any documentation indicating inadequate budgeting or staffing for the FDA as a whole, except for the information you provide below, yet that only pertains to their supplement division, if I read correctly. If we're going to be telling people what the "facts" are, thereby forcing them spend valuable time defending their views, I think backing up our own "facts" with information pertinent to our arguments would be keen.

I'm assuming your following statement is also part of the "facts":

All it would probably take to get the FDA to change its policies on allowing more preventative treatments and NIH funding on research on aging and cognition enhancement is a big enough lobby and pressure from elected officials' constituencies.

If we're pointing out "facts" as you mentioned, you might want to reconsider using the word, “probably."

As you pointed out, the FDA has a “very limited budget,” and “small task force” so, perhaps finger pointing should be done elsewhere; however, as an organization that our government has tasked with the responsibility to protect the general health and wellbeing of the American people, I wouldn’t be so quick to let them off the hook that fast.

Maybe you’re right; it could be the reason that cheap and natural health supplements aren’t as popular as they should be is due to a lack pressure on the FDA and NIH from politicians. But does shifting the FDA's accountability to the shoulders of political officials absolve the FDA of their responsibility? Here is their mission statement as found on their website:

FDA's Mission Statement
The FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health.

Consumer Reports (May 2004) and the “Dirty Dozen” unsafe herbs still readily available

• “CONSUMER REPORTS has identified a dozen (supplements) that … are too dangerous to be on the market. Yet they are.” Introductory paragraph in red ink.

• Factors contributing to unsafe supplements on the market.

• “ ‘The standards for demonstrating a supplement is hazardous are so high that it can take the FDA years to build a case,’ said Bruce Silverglade, legal director of the Center for Science in the Public Interest, a Washington D.C., consumer advocacy group”(pg. 12).

• “The FDA’s supplement division is understaffed and underfunded, with about 60 people and a budget of only 10 million “dollars)…” (pp. 12-13).

• “…Overwhelming opposition from Congress and industry forced it to back down” when the FDA first tried to regulate ephedra in 1997 (pg. 13).

• The public assumes a greater degree of government regulation than exists – in a 2002 Harris Poll of 1010 adults, 59% of respondents believed that supplements must be approved by a government agency before they can be sold to the public, 68% thought the government requires warning labels on supplements with regard to potential dangers, and 55% thought that supplement manufacturers could not make safety claims without solid scientific support.

The FDA implements particularly high standards of evidence, as is discussed here.

Overview of Data and Eligibility for a Qualified Health Claim

A health claim characterizes the relationship between a substance and a disease or health-related condition (21 CFR 101.14(a)(1)).  The substance must be associated with a disease or health-related condition for which the general U.S. population, or an identified U.S. population subgroup is at risk (21 CFR 101.14(b)(1)).  Health claims characterize the relationship between the substance and a reduction in risk of contracting a particular disease.[2]  In a review of a qualified health claim, the agency first identifies the substance and disease or health-related condition that is the subject of the proposed claim and the population to which the claim is targeted.[3]  FDA considers the data and information provided in the petition, in addition to other written data and information available to the agency, to determine whether the data and information could support a relationship between the substance and the disease or health-related condition.[4] 

The agency then separates individual reports of human studies from other types of data and information.  FDA focuses its review on reports of human intervention and observational studies.[5] 

In addition to individual reports of human studies, the agency also considers other types of data and information in its review, such as meta-analyses,[6] review articles,[7] and animal and in vitro studies.  These other types of data and information may be useful to assist the agency in understanding the scientific issues about the substance, the disease or health-related condition, or both, but can not by themselves support a health claim relationship.  Reports that discuss a number of different studies, such as meta-analyses and review articles, do not provide sufficient information on the individual studies reviewed for FDA to determine critical elements such as the study population characteristics and the composition of the products used.  Similarly, the lack of detailed information on studies summarized in review articles and meta-analyses prevents FDA from determining whether the studies are flawed in critical elements such as design, conduct of studies, and data analysis.  FDA must be able to review the critical elements of a study to determine whether any scientific conclusions can be drawn from it.  Therefore, FDA uses meta-analyses, review articles, and similar publications[8] to identify reports of additional studies that may be useful to the health claim review and as background about the substance-disease relationship.  If additional studies are identified, the agency evaluates them individually.

FDA uses animal and in vitro studies as background information regarding mechanisms of action that might be involved in any relationship between the substance and the disease.  The physiology of animals is different than that of humans.  In vitro studies are conducted in an artificial environment and cannot account for a multitude of normal physiological processes such as digestion, absorption, distribution, and metabolism that affect how humans respond to the consumption of foods and dietary substances (Institute of Medicine, National Academies of Science, 2005).  Animal and in vitro studies can be used to generate hypotheses or to explore a mechanism of action but cannot adequately support a relationship between the substance and the disease.

FDA evaluates the individual reports of human studies to determine whether any scientific conclusions can be drawn from each study.  The absence of critical factors such as a control group or a statistical analysis means that scientific conclusions cannot be drawn from the study (Spilker et al., 1991, Federal Judicial Center, 2000).  Studies from which FDA cannot draw any scientific conclusions do not support the health claim relationship, and these are eliminated from further review.

Because health claims involve reducing the risk of a disease in people who do not already have the disease that is the subject of the claim, FDA considers evidence from studies in individuals diagnosed with the disease that is the subject of the health claim only if it is scientifically appropriate to extrapolate to individuals who do not have the disease.  That is, the available scientific evidence must demonstrate that: (1) the mechanism(s) for the mitigation or treatment effects measured in the diseased populations are the same as the mechanism(s) for risk reduction effects in non-diseased populations; and (2) the substance affects these mechanisms in the same way in both diseased people and healthy people.  If such evidence is not available, the agency cannot draw any scientific conclusions from studies that use diseased subjects to evaluate the substance-disease relationship.

Next, FDA rates the remaining human intervention and observational studies for methodological quality.  This quality rating is based on several criteria related to study design (e.g., use of a placebo control versus a non-placebo controlled group), data collection (e.g., type of dietary assessment method), the quality of the statistical analysis, the type of outcome measured (e.g., disease incidence versus validated surrogate endpoint), and study population characteristics other than relevance to the U.S. population (e.g., selection bias and whether  important  information about the study subjects--e.g., age, smoker vs. non-smoker was gathered and reported).  For example, if the scientific study adequately addressed all or most of the above criteria, it would receive a high methodological quality rating.  Moderate or low quality ratings would be given based on the extent of the deficiencies or uncertainties in the quality criteria.  Studies that are so deficient that scientific conclusions cannot be drawn from them cannot be used to support the health claim relationship, and these are eliminated from further review.

Finally, FDA evaluates the results of the remaining studies.  The agency then rates the strength of the total body of publicly available evidence.[9]  The agency conducts this rating evaluation by considering the study type (e.g., intervention, prospective cohort, case-control, cross-sectional), study category , the methodological quality rating previously assigned, the quantity of evidence (number of the various types of studies and sample sizes), whether the body of scientific evidence supports a health claim relationship for  the U.S. population or target subgroup, whether study results supporting the proposed claim have been replicated[10], and the overall consistency[11] of the total body of evidence.[12]  Based on the totality of the scientific evidence, FDA determines whether such evidence is credible to support the substance/disease relationship, and, if so, determines the ranking that reflects the level of comfort among qualified scientists that such a relationship is scientifically valid.

Alright, you've sufficiently argued that the FDA has a stringent drug approval process. Let me point out though, my original argument regarding the FDA had nothing to do with the steps involved when making a decision, but rather in my belief that some of the decisions they make are not with the American people's best interest. I then followed by posting an LEF article which was only intended to bring up, and I quote, "questionable" decisions made by the FDA, and was not intended as a citation to the source of reasoning behind my argument.

I would like to leave it at that, but...

Also, I don't necessarily believe everything (or anything?) I read...and I tend to take an even closer look at evidence when it is presented by companies and/or individuals who have a conflict of interest in selling substances they advocate the use of.

I can't tell if you're implying that I, personally am gullible enough to believe everything I read, or if you're just pointing this out to help me understand your personal heuristics, so I'll give you the benefit of the doubt that you're just helping me to understand your critical approach.

In hindsight, maybe the article isn't the most optimal source for questionable FDA actions, but as I said, it was just posted to foster a questioning attitude toward authority.

[kottke]

Alright so has anyone felt any peripheral side effects off of modafinil (i.e slow breathing-hard breathing, paresthesia, coordination issues). I myself have been taking 100-300mgs a day on and off and thought that these side effects were atributed to the "down-time" of the drug but soon learned that these side effects ocured while on the drug.

The main issue i expereince is almost like hypophonia- which is an abnormally weak voice due to incoordination of the muscles concerned in vocalization. This is especially prevelant when i drink a beer or two on the drug. People cant understand me without me yelling because my voice is so soft. It takes alot of effort to speak....Another issue i experience is when i go to bed at night it becomes very hard to breathe and i sometimes (very rarely) wake up out of nowhere breathing very hard as if i hadnt take one good breathe all night. It would be interesting to know if anyone has shown these effects because it shows strong correlation parkinson like activity which is basically of effect in the striatum as shows in the studies adam posted earlier.

[garethnelsonuk]

Stop drinking.

[kottke]

No garethnelsonuk i am not an avid drinker. My wording was incorrect. Within the time that i have taken modafinil i have also consumed some drinks that when combined made the problem worse. This was kind of reinforcing the fact that it is having a numbing effect on my body. Becuase when i drink without modafinil this does not usually happen. When i do have this effect it is always involed with modafinil either with or without alcohol.

Has anyone expereinced similar effects?

[doug123]

[quote]

Now, to Adam: After reading your posts, it's not clear to me whether your arguments are against my belief that the FDA has made questionable decisions in the past, or if you're just contesting the LEF article. If it is the latter, then by all means, you've certainly driven home the point in that conflicting interests can and do occur, but that's all you've shown - a correlation does not imply causation.

Now, if your following arguements are in response to my original comment regarding questionable decisions made by the FDA, I sense a nice straw-man fallacy.
[/quote]

Jdog, I failed to answer all of your questions; I am sorry; I try to post the news I see early enough in the day so I can get around to reading it and evaluating the possible implications by the end of the day; however, sometimes that is just not possible.

The first sentence of your post was (I guess) directed at Paul (a third year grad. student in clinical trials) -- you asked:

[quote]
If you happen to come accross any new studies about long-term side-effects from modafinil make sure you post it.
[/quote]

I guess I didn't address that because I did not feel it was directed at me.

[quote]
don't think the FDA are necessarily the real problem.
They might be easiest to point the finger at...
[/quote]

[quote]
So, just because someone or something might be the easiest to “point the finger” at, does that mean it shouldn’t be done?
[/quote]

I don't know if you are asking this question literally or figuratively. It depends is the best answer in this case. Please be more specific about who is pointing the finger at whom.

[quote]
The facts are: the USFDA is a very small task force with a very limited budget that acts on laws passed through US legislation.
[/quote]

[quote]
I'm assuming when you say "the USFDA," you're implying the organization as a whole. I haven't seen any documentation indicating inadequate budgeting or staffing for the FDA as a whole, except for the information you provide below, yet that only pertains to their supplement division, if I read correctly. If we're going to be telling people what the "facts" are, thereby forcing them spend valuable time defending their views, I think backing up our own "facts" with information pertinent to our arguments would be keen.
[/quote]

I believe I provided the "fact" I imagine you are referring to in my quotation -- I usually make my posts with the format:

[quote]

(x = primary or secondary source of information*)

In this case, x= http://www.acsu.buff...etyefficacy.htm

[/quote]

In other words, I am telling the reader my source of information -- in this case, this exact information:

[quote]

Consumer Reports (May 2004) and the “Dirty Dozen” unsafe herbs still readily available

· “CONSUMER REPORTS has identified a dozen (supplements) that … are too dangerous to be on the market. Yet they are.” Introductory paragraph in red ink.

· Factors contributing to unsafe supplements on the market.

· “ ‘The standards for demonstrating a supplement is hazardous are so high that it can take the FDA years to build a case,’ said Bruce Silverglade, legal director of the Center for Science in the Public Interest, a Washington D.C., consumer advocacy group”(pg. 12).

· “The FDA’s supplement division is understaffed and underfunded, with about 60 people and a budget of only 10 million “dollars)…” (pp. 12-13).

· “…Overwhelming opposition from Congress and industry forced it to back down” when the FDA first tried to regulate ephedra in 1997 (pg. 13).

· The public assumes a greater degree of government regulation than exists – in a 2002 Harris Poll of 1010 adults, 59% of respondents believed that supplements must be approved by a government agency before they can be sold to the public, 68% thought the government requires warning labels on supplements with regard to potential dangers, and 55% thought that supplement manufacturers could not make safety claims without solid scientific support.
[/quote]

The secondary source of information cited above was from Sanford H. Levy, M.D.'s educational website (one of the best online sources for information on dietary supplements -- worth a look).

I did a little bit of searching and found the Primary Source of information:

Here is a direct link to the article, from which I now will repost, in its entirety:

[quote]

May 2004 
Dangerous supplements: Still at large



If you can buy it at a clean, well-lighted store, if it's “all natural,” it's not going to do you serious harm, right? That's what many Americans assume about dietary supplements. But while most supplements are probably fairly benign, Consumer Reports has identified a dozen that according to government warnings, adverse-event reports, and top experts are too dangerous to be on the market. Yet they are. We easily purchased all 12 in February 2004 in a few days of shopping online and in retail stores.

These unsafe supplements include Aristolochia, an herb conclusively linked to kidney failure and cancer in China, Europe, Japan, and the U.S.; yohimbe, a sexual stimulant linked to heart and respiratory problems; bitter orange, whose ingredients have effects similar to those of the banned weight-loss stimulant ephedra; and chaparral, comfrey, germander, and kava, all known or likely causes of liver failure. (For a complete list of the “dirty dozen,” see
12 supplements to avoid.)

CR Quick Take:

A CR investigation found that many dangerous supplements can easily be purchased in stores and online. Many of these supplements have been banned in other countries. Why can't the U.S. Food and Drug Administration ban these products now?

We found that regulatory barriers created by Congress, supplement-industry pressure, and a lack of resources at the FDA have resulted in major risks for consumers.

• These widely available dietary supplements (see 12 supplements to avoid) may cause cancer, severe kidney or liver damage, heart problems, or even death. They should be avoided by consumers.

• These supplements are sold under a profusion of names, making it difficult for consumers to know what they're purchasing.

• Most also appear in combination products marketed for a broad array of uses, such as aphrodisiacs, athletic-performance boosters, and treatments for anxiety, arthritis, menstrual problems, ulcers, and weight loss.

U.S. consumers shelled out some $76 million in 2002 for just three of these supplements: androstenedione, kava, and yohimbe, the only ones for which sales figures were available, according to the Nutrition Business Journal, which tracks the supplement industry.

The potentially dangerous effects of most of these products have been known for more than a decade, and at least five of them are banned in Asia, Europe, or Canada. Yet until very recently, the U.S. Food and Drug Administration had not managed to remove a single dietary supplement from the market for safety reasons.

After seven years of trying, the agency announced a ban on the weight-loss aid ephedra in December 2003. And in March 2004 it warned 23 companies to stop marketing the body-building supplement androstenedione (andro).

Despite these actions against high-profile supplements, whose dangers were so well known that even industry trade groups had stopped defending them, the agency continues to be hamstrung by the 1994 Dietary Supplement Health and Education Act (DSHEA, pronounced de-shay). While drug manufacturers are required to prove that their products are safe before being marketed, DSHEA makes the FDA prove that supplements on the market are unsafe and denies the agency all but the sketchiest information about the safety record of most of them.

“The standards for demonstrating a supplement is hazardous are so high that it can take the FDA years to build a case,” said Bruce Silverglade, legal director of the Center for Science in the Public Interest, a Washington, D.C., consumer-advocacy group.

At the same time, the FDA’s supplement division is understaffed and underfunded, with about 60 people and a budget of only $10 million to police a $19.4 billion-a-year industry. To regulate drugs, annual sales of which are 12 times the amount of supplement sales, the FDA has almost 43 times as much money and almost 48 times as many people.

“The law has never been fully funded,” said William Hubbard, FDA associate commissioner for policy and planning. “There's never been the resources to do all the things the law would command us to do.”

The agency has learned that it must tread carefully when regulating supplements. The first time it tried to regulate the dangerous stimulant ephedra, in 1997, overwhelming opposition from Congress and industry forced it to back down.

As a result, the FDA is sometimes left practicing what Silverglade calls “regulation by press release”--issuing warnings about dangerous supplements and hoping that consumers and health practitioners
read them.

There are signs of hope. The FDA has said that if the ban on ephedra holds up against likely legal challenges, it plans to go after other harmful supplements. Legislation has been introduced to strengthen the FDA's authority under DSHEA and give the agency more money to enforce the act.

But the supplement marketplace still holds hidden hazards for consumers, especially among products that aren't in the headlines. “Consumers are provided with more information about the composition and nutritional value of a loaf of bread than about the ingredients and potential hazards of botanical medicines,” said Arthur Grollman, M.D., professor of pharmacological sciences at the State University of New York, Stony Brook, and a critic of DSHEA.

A question of safety

Supplement-industry advocates say the ephedra ban demonstrates that DSHEA gives the FDA enough power to protect consumers from unsafe products. “I don't think there's anything wrong except that FDA has only recently begun vigorous and active enforcement of the law,” said Annette Dickinson, Ph.D., president of the Council for Responsible Nutrition, a major trade association for the supplement industry.

But critics of DSHEA think the ban illustrates the extremes to which the FDA must go to outlaw a hazardous product.

When the agency initially tried to rein in ephedra use in 1997, after receiving hundreds of reports of adverse events, it sought not an outright ban but dosage restrictions and sterner warning labels. The industry mounted a furious counter-attack, including the creation of a public-relations group called the Ephedra Education Council and a scientific review from a private consulting firm, commissioned by Dickinson's trade group, that concluded ephedra was safe. After the U.S. General Accounting Office said the FDA “did not establish a causal link” between taking ephedra and deaths or injuries, the agency was forced to drop its proposal.

[quote]
SUFFERED seizure
Gretchen Fitzgerald, age 21, Fort Collins, Colo.

PROBLEM She took Xenadrine EFX “thermogenic” diet pills to boost her energy while studying for final exams, believing they were safe because they were labeled ephedra-free. After three weeks of taking the product she had a seizure. The neurologist consulted told her the bitter orange in the Xenadrine was the probable cause. Xenadrine’s manufacturer did not return our phone calls. Since going off the Xenadrine, Fitzgerald has had no further problems.

[/quote]

The industry continued to vigorously market and defend ephedra. Metabolife International, a leading ephedra manufacturer, did not let the FDA know that it had received 14,684 complaints of adverse events associated with its ephedra product, Metabolife 356, in the previous five years, including 18 heart attacks, 26 strokes, 43 seizures, and 5 deaths. It took the pressure of congressional and Justice Department investigations to get the company to turn over the complaints in 2002. Then Steve Bechler, a pitcher for the Baltimore Orioles, died unexpectedly in 2003 while taking another ephedra supplement, Xenadrine RFA-1. With sales suffering from the bad publicity, manufacturers began to replace ephedra with other stimulants such as bitter orange, which mimics ephedra in chemical composition and function.

“All of a sudden Congress dropped objections to an ephedra ban andstarted demanding the FDA act,” said Silverglade.

To amass the necessary scientific evidence that it hoped would satisfy the demanding standard set by DSHEA, the FDA took aggressive action: It commissioned an outside review from the RAND Corporation, analyzed adverse-event reports, and pored over every available shred of scientific evidence.

“We’ve gone the whole nine yards to collect and evaluate all the possible evidence,” Mark McClellan, commissioner of the FDA, said in announcing the ban. “We will be doing our best to defend this in court, and if that’s not sufficient, it may be time to re-examine the act.”

Drugs vs. supplements

In an October 2002 nationwide Harris Poll of 1,010 adults, 59 percent of respondents said they believed that supplements must be approved by a government agency before they can be sold to the public. Sixty-eight percent said the government requires warning labels on supplements’ potential side effects or dangers. Fifty-five percent said supplement manufacturers can’t make safety claims without solid scientific support.

They were wrong. None of those protections exist for supplements--only for prescription and over-the-counter medicines. Here are the major differences in the safety regulations:

Testing for hazards. Before approval, drugs must be proved effective, with an acceptable safety profile, by means of lab research and rigorous human clinical trials involving a minimum of several thousand people, many millions of dollars, and several years.

In contrast, supplement manufacturers can introduce new products without any testing for safety and efficacy. The maker’s only obligation is to send the FDA a copy of the language on the label (see
Supplement labels).

“Products regulated by DSHEA were presumed to be safe because of their long history of use, often in other countries,” said Jane E. Henney, M.D., commissioner of the FDA from 1998 to 2001. “As their use dramatically increased in this country after the passage of DSHEA, the presumption of safety may have been misplaced, particularly for products other than traditional vitamins and minerals. Some, like ephedra, act like drugs and thus have similar risks.”

The only exceptions to this “presumption of safety” are supplement ingredients that weren’t being sold in the U.S. when DSHEA took effect. Makers of such “new dietary ingredients” must show the FDA evidence of the products’ safety before marketing them. The FDA invoked that rarely used provision in its action against androstenedione. After years of allowing andro to be marketed without restriction, the agency declared that it was “not aware” that the supplement was used before DSHEA, so it couldn’t be sold without evidence of safety.

Disclosing the risks. Drug labels and package inserts must mention all possible adverse effects and interactions. But supplement makers don’t have to put safety warnings on the labels, even for products with known serious hazards.

We bought a product called Relaxit whose label had no warning about the kava it contained, even though the American Herbal Products Association, an industry trade group, recommends a detailed, though voluntary warning label about potential liver toxicity on all kava products.

Ensuring product quality. Drugs must conform to “good manufacturing practices” that guarantee that their contents are pure and in the quantities stated on the label. While DSHEA gave the FDA authority to impose similar standards on supplements, it took until 2003 for the agency to propose regulations--as yet not final--to implement that part of the law.

Contaminants, too, regularly turn up in supplements. In 1998 Richard Ko, Ph.D., of the California Department of Health Services reported that 32 percent of the Asian patent medicines he tested contained pharmaceuticals or heavy metals that weren’t on the label. In 2002, the FDA oversaw a voluntary manufacturer recall of a "prostate health" supplement called PC SPES that, according to tests by the California department, contained a powerful prescription blood thinner, warfarin.

Reporting the problems. By law, drug companies are required to tell the FDA about any reports of product-related adverse events that they receive from any source. Almost every year, drugs are removed from the market based on safety risks that first surfaced in those reports.

In contrast, supplement makers don’t have to report adverse events. Indeed, in the five years after DSHEA took effect, 1994 to 1999, fewer than 10 of the more than 2,500 reports that the FDA received came from manufacturers, according to a 2001 estimate from the inspector general of the U.S. Department of Health and Human Services. (Other sources of reports included consumers, health practitioners, and poison-control centers.) Overall, the FDA estimates that it learns of less than 1 percent of adverse events involving dietary supplements.

THE ‘NATURAL’ MYSTIQUE

Many makers market their supplements as “natural,” exploiting assumptions that such products can’t harm you. That’s a dangerous assumption, said Lois Swirsky Gold, Ph.D., director of the Carcinogenic Potency Project at the University of California, Berkeley, and an expert on chemical carcinogens. “Natural is hemlock, natural is arsenic, natural is poisonous mushrooms,” she said.

A cautionary example is aristolochic acid, which occurs naturally in species of Aristolochia vines that grow wild in many parts of the world. In addition to being a powerful kidney toxin, it is on the World Health Organization’s list of human carcinogens. “It’s one of the most potent chemicals of 1,400 in my Carcinogenic Potency Database,” Gold said. “People have taken high doses similar to the doses that animals are given in tests, and they both get tumors very quickly.”

[quote]
KIDNEYS FAILED
Beverly Hames, age 59, Beaverton, Ore.

PROBLEM Hames went to an acupuncturist in 1992 seeking a “safe, natural” treatment for an aching back. She got a selection of Chinese herbal products, at least five of which were later found to contain aristolochic acid. By mid-1994, she had symptoms of kidney failure, and in 1996 she underwent a kidney transplant. She must take anti-rejection drugs (below) for life. The herbs’ distributor said his Chinese suppliers had substituted Aristolochia for another herb without his knowledge.

[/quote]

The dangers of aristolochic acid have been known since at least 1993, when medical-journal articles began appearing about 105 patrons of a Belgian weight-loss clinic who had suffered kidney failure after consuming Chinese herbs adulterated with Aristolochia. At least 18 of the women also subsequently developed cancer near
the kidney.

These findings prompted the FDA to issue a nationwide warning against Aristolochia in 2001 and to impose a ban on further imports of the herb. But in early 2004, more than two years after the import ban went into effect, Consumer Reports was able to purchase products online that were labeled as containing Aristolochia.
In 2003, Gold identified more than 100 products for sale online with botanical ingredients listed by the FDA as known or suspected to contain aristolochic acid.

Donna Andrade-Wheaton, a former aerobics instructor in Rhode Island, learned those facts too late to save her kidneys. After taking Chinese herbs containing Aristolochia for more than two years, she suffered severe kidney damage; her kidney tissues were found to contain aristolochic acid. In late 2002, at age 39, she underwent a kidney transplant.

Andrade-Wheaton is suing both the acupuncturist who gave her the herbs and several companies that manufactured them. The acupuncturist declined to discuss the case on the record, and the manufacturer did not return our phone calls.

There’s another widespread and false assumption about natural supplements: that they’re always pure, unprocessed products of the earth. Because DSHEA permits the marketing of concentrates and extracts, supplement makers can and do manipulate ingredients to increase the concentrations of pharmacologically active compounds.

That’s especially true of the many weight-loss supplements designed for “thermogenic” stimulant effects--boosting calorie expenditure by revving the metabolic rate.

On one Internet shopping tour, for instance, we bought a product called Thermorexin--”the Hottest new Thermogenic on the market!” Its label says it contains, among its 22 ingredients, 30 milligrams of theophylline derived from a black tea extract and the stimulant bitter orange. Sold as Theo-Dur and other brands, theophylline is a prescription drug and an effective asthma treatment, but most doctors seldom prescribe it because it can cause seizures and irregular heartbeats at relatively low doses.

Larry Berube, president of Anafit, Thermorexin’s manufacturer, based in Orlando, Fla., described how the product’s combination of ingredients was developed: “Once we find out that the FDA says it’s OK, we put them together in the lab, run our tests, and do our trials, and if it comes up good, we capsulate it, put it online and in the stores and sell it,” he said.

Those tests involved asking fitness professionals to use the supplement, and measuring their heart rate and blood pressure, Berube said. The company doesn’t use a control group, he said. Then “we go to the fitness discussion boards and let trainers and people know we have a new product and do they want to try it,” he said. “And then they try it, and they report back.” Berube said he has not heard of any bad reactions to Thermorexin.

[quote]
KIDNEYS FAILED
Donna Andrade-Wheaton, age 40, Cranston, R.I.


PROBLEM Andrade-Wheaton’s acupuncturist prescribed more than a half dozen Chinese herbal supplements to treat health conditions, including endometriosis. At least one of the products listed Aristolochia as an ingredient, even after the FDA issued a nationwide Aristolochia safety warning in 2001. She underwent a kidney transplant in September 2002 and must take anti-rejection drugs (below) for life.

[/quote]

Copyright © 2000-2006 Consumers Union of U.S., Inc. No reproduction, in whole or in part, without written permission.
[/quote]

[quote]
I'm assuming your following statement is also part of the "facts":
[/quote]

[quote]
All it would probably take to get the FDA to change its policies on allowing more preventative treatments and NIH funding on research on aging and cognition enhancement is a big enough lobby and pressure from elected officials' constituencies.
[/quote]

[quote]
If we're pointing out "facts" as you mentioned, you might want to reconsider using the word, “probably."

As you pointed out, the FDA has a “very limited budget,” and “small task force” so, perhaps finger pointing should be done elsewhere; however, as an organization that our government has tasked with the responsibility to protect the general health and wellbeing of the American people, I wouldn’t be so quick to let them off the hook that fast.
[/quote]

The "limited budget" comment and "small task force" comments were based on the Consumer Reports article, which I trust is an accurate depiction of the data; for one, they have no reason to misrepresent the data.

Recall -- I stated:

[quote]
All it would probably take to get the FDA to change its policies on allowing more preventative treatments and NIH funding on research on aging and cognition enhancement is a big enough lobby and pressure from elected officials' constituencies.
[/quote]

The NIH is quite specific about the procedures to allot US research dollars. Independent funding doesn't come easy.

[quote]
Maybe you’re right; it could be the reason that cheap and natural health supplements aren’t as popular as they should be is due to a lack pressure on the FDA and NIH from politicians. But does shifting the FDA's accountability to the shoulders of political officials absolve the FDA of their responsibility? Here is their mission statement as found on their website:

FDA's Mission Statement
The FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health.
[/quote]

Naturally, understanding simple economic principles, we should expect some trade off between regulation of supplements (safety?) and their cost. Of course there is incentive for independent organizations such as Consumerlab.com to spring up and charge consumers $27 per year to access independent testing results on natural supplements. Then the real issue would be to consider if you as an average supplement consumer spend enough $ on supplements to justify $27/yr. Maybe you and your friend or member of your family can share a membership. And it is not illegal for more organizations to perform independent testing if they choose. Of course, we expect the supplement lobby to offer spin in the contrary directions. Whenever one can clearly see funding from supplement companies to support a particular viewpoint, one might consider our dear friend "Conflict of Interest." [wis]

[quote]
The FDA implements particularly high standards of evidence, as is discussed here.
[/quote]

[quote]
Overview of Data and Eligibility for a Qualified Health Claim

A health claim characterizes the relationship between a substance and a disease or health-related condition (21 CFR 101.14(a)(1)).  The substance must be associated with a disease or health-related condition for which the general U.S. population, or an identified U.S. population subgroup is at risk (21 CFR 101.14(b)(1)).  Health claims characterize the relationship between the substance and a reduction in risk of contracting a particular disease.[2]  In a review of a qualified health claim, the agency first identifies the substance and disease or health-related condition that is the subject of the proposed claim and the population to which the claim is targeted.[3]  FDA considers the data and information provided in the petition, in addition to other written data and information available to the agency, to determine whether the data and information could support a relationship between the substance and the disease or health-related condition.[4] 

The agency then separates individual reports of human studies from other types of data and information.  FDA focuses its review on reports of human intervention and observational studies.[5] 

In addition to individual reports of human studies, the agency also considers other types of data and information in its review, such as meta-analyses,[6] review articles,[7] and animal and in vitro studies.  These other types of data and information may be useful to assist the agency in understanding the scientific issues about the substance, the disease or health-related condition, or both, but can not by themselves support a health claim relationship.  Reports that discuss a number of different studies, such as meta-analyses and review articles, do not provide sufficient information on the individual studies reviewed for FDA to determine critical elements such as the study population characteristics and the composition of the products used.  Similarly, the lack of detailed information on studies summarized in review articles and meta-analyses prevents FDA from determining whether the studies are flawed in critical elements such as design, conduct of studies, and data analysis.  FDA must be able to review the critical elements of a study to determine whether any scientific conclusions can be drawn from it.  Therefore, FDA uses meta-analyses, review articles, and similar publications[8] to identify reports of additional studies that may be useful to the health claim review and as background about the substance-disease relationship.  If additional studies are identified, the agency evaluates them individually.

FDA uses animal and in vitro studies as background information regarding mechanisms of action that might be involved in any relationship between the substance and the disease.  The physiology of animals is different than that of humans.  In vitro studies are conducted in an artificial environment and cannot account for a multitude of normal physiological processes such as digestion, absorption, distribution, and metabolism that affect how humans respond to the consumption of foods and dietary substances (Institute of Medicine, National Academies of Science, 2005).  Animal and in vitro studies can be used to generate hypotheses or to explore a mechanism of action but cannot adequately support a relationship between the substance and the disease.

FDA evaluates the individual reports of human studies to determine whether any scientific conclusions can be drawn from each study.  The absence of critical factors such as a control group or a statistical analysis means that scientific conclusions cannot be drawn from the study (Spilker et al., 1991, Federal Judicial Center, 2000).  Studies from which FDA cannot draw any scientific conclusions do not support the health claim relationship, and these are eliminated from further review.

Because health claims involve reducing the risk of a disease in people who do not already have the disease that is the subject of the claim, FDA considers evidence from studies in individuals diagnosed with the disease that is the subject of the health claim only if it is scientifically appropriate to extrapolate to individuals who do not have the disease.  That is, the available scientific evidence must demonstrate that: (1) the mechanism(s) for the mitigation or treatment effects measured in the diseased populations are the same as the mechanism(s) for risk reduction effects in non-diseased populations; and (2) the substance affects these mechanisms in the same way in both diseased people and healthy people.  If such evidence is not available, the agency cannot draw any scientific conclusions from studies that use diseased subjects to evaluate the substance-disease relationship.

Next, FDA rates the remaining human intervention and observational studies for methodological quality.  This quality rating is based on several criteria related to study design (e.g., use of a placebo control versus a non-placebo controlled group), data collection (e.g., type of dietary assessment method), the quality of the statistical analysis, the type of outcome measured (e.g., disease incidence versus validated surrogate endpoint), and study population characteristics other than relevance to the U.S. population (e.g., selection bias and whether  important  information about the study subjects--e.g., age, smoker vs. non-smoker was gathered and reported).  For example, if the scientific study adequately addressed all or most of the above criteria, it would receive a high methodological quality rating.  Moderate or low quality ratings would be given based on the extent of the deficiencies or uncertainties in the quality criteria.  Studies that are so deficient that scientific conclusions cannot be drawn from them cannot be used to support the health claim relationship, and these are eliminated from further review.

Finally, FDA evaluates the results of the remaining studies.  The agency then rates the strength of the total body of publicly available evidence.[9]  The agency conducts this rating evaluation by considering the study type (e.g., intervention, prospective cohort, case-control, cross-sectional), study category , the methodological quality rating previously assigned, the quantity of evidence (number of the various types of studies and sample sizes), whether the body of scientific evidence supports a health claim relationship for  the U.S. population or target subgroup, whether study results supporting the proposed claim have been replicated[10], and the overall consistency[11] of the total body of evidence.[12]  Based on the totality of the scientific evidence, FDA determines whether such evidence is credible to support the substance/disease relationship, and, if so, determines the ranking that reflects the level of comfort among qualified scientists that such a relationship is scientifically valid.
[/quote]

[quote]
Alright, you've sufficiently argued that the FDA has a stringent drug approval process. Let me point out though, my original argument regarding the FDA had nothing to do with the steps involved when making a decision, but rather in my belief that some of the decisions they make are not with the American people's best interest. I then followed by posting an LEF article which was only intended to bring up, and I quote, "questionable" decisions made by the FDA, and was [b]not intended as a citation to the source of reasoning behind my argument.

I would like to leave it at that, but...
[/quote]


[quote]
Also, I don't necessarily believe everything (or anything?) I read...and I tend to take an even closer look at evidence when it is presented by companies and/or individuals who have a conflict of interest in selling substances they advocate the use of.
[/quote]

[quote]
I can't tell if you're implying that I, personally am gullible enough to believe everything I read, or if you're just pointing this out to help me understand your personal heuristics, so I'll give you the benefit of the doubt that you're just helping me to understand your critical approach.

In hindsight, maybe the article isn't the most optimal source for questionable FDA actions, but as I said, it was just posted to foster a questioning attitude toward authority.

[/quote]

One of my friends told me "don't believe anything you hear and only half of what your read." I try my best.

Take care.

[impulsive]

no1 knows anything.... thats why you "dont" follow people

or, "learn from their mistakes"

everything in life is a risk...

To impulsive: Wise man once say, "A stupid man dosen't learn from his mistakes. A smart man learns from his mistakes. A wise man learns from others mistakes."

Well, thats just finishing what I started [wis]

agreed [thumb]

[jdog]

Touché...on myself then...? [hmm] [lol]

The "/endthread" threw me off there. Gave me the impression you thought that knowledge is futile. My bad.

[impulsive]

I agree to what you have mentioned [glasses]

[esmith]

Also, are you able to get to sleep at night on that dosage?

I just got a package of Modalert this week. On tuesday, took 200 mg around noon, 100 mg at 8 pm, 100 mg at midnight. This dose was enough to prevent me from feeling sleepy and even from being able to sleep. I did fall asleep eventually toward the morning, slept for 1.5 hours and then woke up by myself, reasonably fresh and unable to fall asleep again. ( Normally I sleep 8-9 hours a day )

So either 1) i'm hypersensitive to modafinil, 2) i was lucky and my lot of Modalert was reasonably pure, or 3) Modalert isn't as bad as some people say.

I think you should be able to sleep at night if you take it early enough, like before noon. I also read somewhere that if you take it
just before going to sleep, you'll wake up after sleeping for 4-5 hours.

Do you know if there's a huge crash if you stay awake for say, 40 hours?

What about when you do go to bed? Do you need extra hours of sleep in order for your body to recouperate after staying awake that long?

No crash, just getting progressively more tired as the drug wears off. You may need a bit more sleep than usual ( but less than after a normal all-nighter ). Some people say you don't accrue any sleep debt by cutting on your sleep with Modafinil. I think it's partially true.

Edited by esmith, 12 January 2007 - 01:26 AM.

[jdog]

Now this is the info I'm looking for. Thanks, and let me know if anything changes once you've gotten back to your regular sleep routine.