Sugary Drinks as the Culprit in Childhood Obesity? a RCT among Primary School Children

24 09 2012

ResearchBlogging.org Childhood obesity is a growing health problem. Since 1980, the proportion of overweighted children has almost tripled in the USA:  nowadays approximately 17% of children and adolescents are obese.  (Source: cdc.gov [6])

Common sense tells me that obesity is the result of too high calory intake without sufficient physical activity.” - which is just what the CDC states. I’m not surprised that the CDC also mentions the greater availability of high-energy-dense foods and sugary drinks at home and at school as main reasons for the increased intake of calories among children.

In my teens I already realized that sugar in sodas were just “empty calories” and I replaced tonic and cola by low calory  Rivella (and omitted sugar from tea). When my children were young I urged the day care to restrain from routinely giving lemonade (often in vain).

I was therefore a bit surprised to notice all the fuss in the Dutch newspapers [NRC] [7] about a new Dutch study [1] showing that sugary drinks contributed to obesity. My first reaction was “Duhhh?!…. so what?”.

Also, it bothered me that the researchers had performed a RCT (randomized controlled trial) in kids giving one half of them sugar-sweetened drinks and the other half sugar-free drinks. “Is it ethical to perform such a scientific “experiment” in healthy kids?”, I wondered, “giving more than 300 kids 14 kilo sugar over 18 months, without them knowing it?”

But reading the newspaper and the actual paper[1], I found that the study was very well thought out. Also ethically.

It is true that the association between sodas and weight gain has been shown before. But these studies were either observational studies, where one cannot look at the effect of sodas in isolation (kids who drink a lot of sodas often eat more junk food and watch more television: so these other life style aspects may be the real culprit) or inconclusive RCT’s (i.e. because of low sample size). Weak studies and inconclusive evidence will not convince policy makers, organizations and beverage companies (nor schools) to take action.

As explained previously in The Best Study Design… For Dummies [8] the best way to test whether an intervention has a health effect is to do a  double blind RCT, where the intervention (in this case: sugary drinks) is compared to a control (drinks with artificial sweetener instead of sugar) and where the study participants, and direct researchers do not now who receives the  actual intervention and who the phony one.

The study of Katan and his group[1] was a large, double blinded RCT with a long follow-up (18 months). The researchers recruited 641 normal-weight schoolchildren from 8 primary schools.

Importantly, only children were included in the study that normally drank sugared drinks at school (see announcement in Dutch). Thus participation in the trial only meant that half of the children received less sugar during the study-period. The researchers would have preferred drinking water as a control, but to ensure that the sugar-free and sugar-containing drinks tasted and looked essentially the same they used an artificial sweetener as a control.

The children drank 8 ounces (250 ml) of a 104-calorie sugar-sweetened or no-calorie sugar-free fruit-flavoured drink every day during 18 months.  Compliance was good as children who drank the artificially sweetened beverages had the expected level of urinary sucralose (sweetener).

At the end of the study the kids in the sugar-free group gained a kilo less weight than their peers. They also had a significant lower BMI-increase and gained less body fat.

Thus, according to Katan in the Dutch newspaper NRC[7], “it is time to get rid of the beverage vending machines”. (see NRC [6]).

But does this research really support that conclusion and does it, as some headlines state [9]: “powerfully strengthen the case against soda and other sugary drinks as culprits in the obesity epidemic?”

Rereading the paper I wondered as to the reasons why this study was performed.

If the trial was meant to find out whether putting children on artificially sweetened beverages (instead of sugary drinks) would lead to less fat gain, then why didn’t the researchers do an  intention to treat (ITT) analysis? In an ITT analysis trial participants are compared–in terms of their final results–within the groups to which they were initially randomized. This permits the pragmatic evaluation of the benefit of a treatment policy.
Suppose there were more dropouts in the intervention group, that might indicate that people had a reason not to adhere to the treatment. Indeed there were many dropouts overall: 26% of the children had stopped consuming the drinks, 29% from the sugar-free group, and 22% from the sugar group.
Interestingly, the majority of the children who stopped drinking the cans because they no longer liked the drink (68/94 versus 45/70 dropouts in the sugar-free versus the sugar group).
Ànd children who correctly assumed that the sweetened drinks were “artificially sweetened” was 21% higher than expected by chance (correct identification was 3% lower in the sugar group).
Did some children stop using the non-sugary drinks because they found the taste less nice than usual or artificial? Perhaps.

This  might indicate that replacing sugar-drinks by artificially sweetened drinks might not be as effective in “practice”.

Indeed most of the effect on the main outcome, the differences in BMI-Z score (the number of standard deviations by which a child differs from the mean in the Netherland for his or her age or sex) was “strongest” after 6 months and faded after 12 months.

Mind you, the researchers did neatly correct for the missing data by multiple imputation. As long as the children participated in the study, their changes in body weight and fat paralleled those of children who finished the study. However, the positive effect of the earlier use of non-sugary drinks faded in children who went back to drinking sugary drinks. This is not unexpected, but it underlines the point I raised above: the effect may be less drastic in the “real world”.

Another (smaller) RCT, published in the same issue of the NEJM [2](editorial in[4]), aimed to test the effect of an intervention to cut the intake of sugary drinks in obese adolescents. The intervention (home deliveries of bottled water and diet drinks for one year) led to a significant reduction in mean BMI (body mass index), but not in percentage body fat, especially in Hispanic adolescents. However at one year follow up (thus one year after the intervention had stopped) the differences between the groups evaporated again.

But perhaps the trial was “just” meant as a biological-fysiological experiment, as Hans van Maanen suggested in his critical response in de Volkskrant[10].

Indeed, the data actually show that sugar in drinks can lead to a greater increase in obesity-related parameters (and vice versa). [avoiding the endless fructose-glucose debate [11].

In the media, Katan stresses the mechanistic aspects too. He claims that children who drank the sweetened drinks, didn’t compensate for the lower intake of sugars by eating more. In the NY-times he is cited as follows[12]: “When you change the intake of liquid calories, you don’t get the effect that you get when you skip breakfast and then compensate with a larger lunch…”

This seems a logic explanation, but I can’t find any substatation in the article.

Still “food intake of the children at lunch time, shortly after the morning break when the children have consumed the study drinks”, was a secondary outcome in the original protocol!! (see the nice comparison of the two most disparate descriptions of the trial design at clinicaltrials.gov [5], partly shown in the figure below).

“Energy intake during lunchtime” was later replaced by a “sensory evaluation” (with questions like: “How satiated do you feel?”). The results, however were not reported in their current paper. That is also true for a questionnaire about dental health.

Looking at the two protocol versions I saw other striking differences. At 2009_05_28, the primary outcomes of the study are the children’s body weight (BMI z-score),waist circumference (replaced by waist to height), skin folds and bioelectrical impedance.
The latter three become secondary outcomes in the final draft. Why?

Click to enlarge (source Clinicaltrials.gov [5])

It is funny that although the main outcome is the BMI z score, the authors mainly discuss the effects on body weight and body fat in the media (but perhaps this is better understood by the audience).

Furthermore, the effect on weight is less then expected: 1 kilo instead of 2,3 kilo. And only a part is accounted for by loss in body fat: -0,55 kilo fat as measured by electrical impedance and -0,35 kilo as measured by changes in skinfold thickness. The standard deviations are enormous.

Look for instance at the primary end point (BMI z score) at 0 and 18 months in both groups. The change in this period is what counts. The difference in change between both groups from baseline is -0,13, with a P value of 0.001.

(data are based on the full cohort, with imputed data, taken from Table 2)

Sugar-free group : 0.06±1.00  [0 Mo]  –> 0.08±0.99 [18 Mo] : change = 0.02±0.41  

Sugar-group: 0.01±1.04  [0 Mo]  –> 0.15±1.06 [18 Mo] : change = 0.15±0.42 

Difference in change from baseline: −0.13 (−0.21 to −0.05) P = 0.001

Looking at these data I’m impressed by the standard deviations (replaced by standard errors in the somewhat nicer looking fig 3). What does a value of 0.01 ±1.04 represent? There is a looooot of variation (even though BMI z is corrected for age and sex). Although no statistical differences were found for baseline values between the groups the “eyeball test” tells me the sugar- group has a slight “advantage”. They seem to start with slightly lower baseline values (overall, except for body weight).

Anyway, the changes are significant….. But significance isn’t identical to relevant.

At a second look the data look less impressive than the media reports.

Another important point, raised by van Maanen[10], is that the children’s weight increases more in this study than in the normal Dutch population. 6-7 kilo instead of 3 kilo.

In conclusion, the study by the group of Katan et al is a large, unique, randomized trial, that looked at the effects of replacement of sugar by artificial sweeteners in drinks consumed by healthy school children. An effect was noticed on several “obesity-related parameters”, but the effects were not large and possibly don’t last after discontinuation of the trial.

It is important that a single factor, the sugar component in beverages is tested in isolation. This shows that sugar itself “does matter”. However, the trial does not show that sugary drinks are the main obesity  factor in childhood (as suggested in some media reports).

It is clear that the investigators feel very engaged, they really want to tackle the childhood obesity problem. But they should separate the scientific findings from common sense.

The cans fabricated for this trial were registered under the trade name Blikkie (Dutch for “Little Can”). This was to make sure that the drinks would never be sold by smart business guys using the slogan: “cans which have scientifically been proven to help to keep your child lean and healthy”.[NRC]

Still soft drink stakeholders may well argue that low calory drinks are just fine and that curbing sodas is not the magic bullet.

But it is a good start, I think.

Photo credits Cola & Obesity:  Melliegrunt Flikr [CC]

  1. de Ruyter JC, Olthof MR, Seidell JC, & Katan MB (2012). A Trial of Sugar-free or Sugar-Sweetened Beverages and Body Weight in Children. The New England journal of medicine PMID: 22998340
  2. Ebbeling CB, Feldman HA, Chomitz VR, Antonelli TA, Gortmaker SL, Osganian SK, & Ludwig DS (2012). A Randomized Trial of Sugar-Sweetened Beverages and Adolescent Body Weight. The New England journal of medicine PMID: 22998339
  3. Qi Q, Chu AY, Kang JH, Jensen MK, Curhan GC, Pasquale LR, Ridker PM, Hunter DJ, Willett WC, Rimm EB, Chasman DI, Hu FB, & Qi L (2012). Sugar-Sweetened Beverages and Genetic Risk of Obesity. The New England journal of medicine PMID: 22998338
  4. Caprio S (2012). Calories from Soft Drinks – Do They Matter? The New England journal of medicine PMID: 22998341
  5. Changes to the protocol http://clinicaltrials.gov/archive/NCT00893529/2011_02_24/changes
  6. Overweight and Obesity: Childhood obesity facts  and A growing problem (www.cdc.gov)
  7. NRC Wim Köhler Eén kilo lichter.NRC | Zaterdag 22-09-2012 (http://archief.nrc.nl/)
  8.  The Best Study Design… For Dummies (http://laikaspoetnik.wordpress.com)
  9. Studies point to sugary drinks as culprits in childhood obesity – CTV News (ctvnews.ca)
  10. Hans van Maanen. Suiker uit fris, De Volkskrant, 29 september 2012 (freely accessible at http://www.vanmaanen.org/)
  11. Sugar-Sweetened Beverages, Diet Coke & Health. Part I. (http://laikaspoetnik.wordpress.com)
  12. Roni Caryn Rabina. Avoiding Sugared Drinks Limits Weight Gain in Two Studies. New York Times, September 21, 2012




Yet Another Negative Trial with Vitamins in Prostate Cancer: Vitamins C and E.

15 12 2008

Within a week after the large SELECT (Selenium and Vitamin E Cancer Prevention) Trial was halted due to disappointing results (see previous posts: [1] and [2]), the negative results of yet another large vitamin trial were announced [7].
Again, no benefits were found from either vitamin C or E when it came to preventing prostate ànd other cancers.
Both trials are now prepublished in JAMA. The full text articles and the accompanying editorial are freely available [3, 4, 5].

In The Physicians’ Health Study II Randomized Controlled Trial (PHS II), researchers tested the impact of regular vitamin E and C supplements on cancer rates among 14,641 male physicians over 50: 7641 men from the PHS I study and 7000 new physicians.

The man were randomly assigned to receive vitamin E, vitamin C, or a placebo. Besides vitamin C or E, beta carotene and/or multivitamins were also tested, but beta carotene was terminated on schedule in 2003 and the multivitamin component is continuing at the recommendation of the data and safety monitoring committee.

Similar to the SELECT trial this RCT had a factorial (2×2) design with respect to the vitamins E and C [1]: randomization yielded 4 nearly equal-sized groups receiving:

  • 400-IU synthetic {alpha}-tocopherol (vitamin E), every other day and placebo (similar to the SELECT trial)
  • 500-mg synthetic ascorbic acid (vitamin C), daily and placebo
  • both active agents
  • both placebos.

Over 8 years, taking vitamin E had no impact at all on rates of either prostate cancer (the primary outcome for vitamin E), or cancer in general. Vitamin C had no significant effect on total cancer (primary outcome for vitamin C) and prostate cancer. Neither was there an effect of vitamin E and/or C on other site-specific cancers.

How can the negative results be explained in the light of the positive results of earlier trials?

  • The conditions may differ from the positive trials:
    • The earlier positive trials had less methodological rigor. These were either observational studies or prostate cancer was not their primary outcome (and may therefore be due to chance). (See previous post The best study design for dummies).
    • Clinical data suggest that the positive effect of vitamin E observed in earlier trials was limited to smokers and/or people with low basal levels of vitamin E, whereas animal models suggest that vitamin E is efficacious against high fat-promoted prostate cancer growth (20), but lacks chemopreventive effects (i.e. see [1,4] and references in [5], a preclinical study we published in 2006).
      Indeed, there were very low levels of smoking in the PHS II study and the effect of the vitamins was mainly assessed on induction not on progression of prostate cancer.
    • Eight times higher vitamin E doses (400IE) have been used than in the ATCB study showing a benefit for vitamin E in decreasing prostate cancer risk! [1,4]
  • Other forms of vitamin E and selenium have been proposed to be more effective.
  • As Gann noted in the JAMA-editorial, the men in both recent studies were highly motivated and had good access to care. In SELECT, the majority of men were tested for PSA each year. Probably because of this intense surveillance, the mean PSA at diagnosis was low and prostate cancers were detected in an early, curable stage. Strikingly, there was only 1 death from prostate cancer in SELECT, whereas appr. 75-100 deaths were expected. There also were indications of a deficit in advanced prostate cancer in PHS II, although a much smaller one.
    In other words (Gann):
    “how can an agent be shown to prevent serious, clinically significant prostate cancers when PSA testing may be rapidly removing those cancers from the population at risk before they progress?”
  • Similarly, in the SELECT trial there was no constraint on the use of other multivitamins and both studies put no restriction on the diet. Indeed the group of physicians who participated in the PHS II trial were healthier overall and ate a more nutritious diet. Therefore Dr Shao wondered
    “Do we really have a placebo group – people with zero exposure? None of these physicians had zero vitamin C and E” [7]. In the Netherlands we were not even able to perform a small phase II trial with certain nutrients for the simple reason that most people already took them.

What can we learn from these negative trials (the SELECT trial and this PHS II-trial)?

  • Previous positive results were probably due to chance. In the future a better preselection of compounds and doses in Phase 2 trials should determine which few interventions make it through the pipeline (Gann, Schroder).
  • Many other trials disprove the health benefits of high dose vitamins and some single vitamins may even increase risks for specific cancers, heart disease or mortality [9]. In addition vitamin C has recently been shown to interfere with cancer treatment [10].
  • The trials make it highly unlikely that vitamins prevent the development of prostate cancer (or other cancers) when given as a single nutrient intervention. Instead, as Dr Sasso puts it “At the end of the day this serves as a reminder that we should get back to basics: keeping your body weight in check, being physically active, not smoking and following a good diet.”
  • Single vitamins or high dose vitamins/antioxidants should not be advised to prevent prostate cancer (or any other cancer). Still it is very difficult to convince people not taking supplements.
  • Another issue is that all kind of pharmaceutical companies keep on pushing the sales of these “natural products”, selectively referring to positive results only. It is about time to regulate this.

1937004448_dfcf7d149f-vitamines-op-een-bordje1

Sources & other reading (click on grey)

  1. Huge disappointment: Selenium and Vitamin E fail to Prevent Prostate Cancer.(post on this blog about the SELECT trial)
  2. Podcasts: Cochrane Library and MedlinePlus: (post on this blog)
  3. Vitamins E and C in the Prevention of Prostate and Total Cancer in Men: The Physicians’ Health Study II Randomized Controlled Trial. J. Michael Gaziano et al JAMA. 2008;0(2008):2008862-11.[free full text]
  4. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial. Scott M. Lippman, Eric A. Klein et al (SELECT)JAMA. 2008;0(2008):2008864-13 [free full text].
  5. Randomized Trials of Antioxidant Supplementation for Cancer Prevention: First Bias, Now Chance-Next, Cause. Peter H. Gann JAMA. 2008;0(2008):2008863-2 [free full text].
  6. Combined lycopene and vitamin E treatment suppresses the growth of PC-346C human prostate cancer cells in nude mice. Limpens J, Schröder FH, et al. J Nutr. 2006 May;136(5):1287-93 [free full text].

    News
  7. The New York Times (2008/11/19) Study: Vitamins E and C Fail to Prevent Cancer in Men.
  8. BBC news: (2008/12/10) Vitamins ‘do not cut cancer risk’.
  9. The New York Times (2008/11/20) News keeps getting worse for vitamins.
  10. The New York Times (2008/10/01) Vitamin C may interfere with cancer treatment.








Huge disappointment: Selenium and Vitamin E fail to Prevent Prostate Cancer.

16 11 2008

select

October 27th the news was released that ([see here for entire announcement from nih.gov]

“an initial, independent review of study data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT), funded by the National Cancer Institute (NCI) and other institutes that comprise the National Institutes of Health shows that selenium and vitamin E supplements, taken either alone or together, did not prevent prostate cancer. The data also showed two concerning trends: a small but not statistically significant increase in the number of prostate cancer cases among the over 35,000 men age 50 and older in the trial taking only vitamin E and a small, but not statistically significant increase in the number of cases of adult onset diabetes in men taking only selenium. Because this is an early analysis of the data from the study, neither of these findings proves an increased risk from the supplements and both may be due to chance.”

SELECT is the second large-scale study of chemoprevention for prostate cancer. Chemoprevention or chemoprophylaxis refers to the administration of a medication to prevent disease. The SELECT trial aimed to determine whether dietary supplementation with selenium and/or vitamin E could reduce the risk of prostate cancer among healthy men. It is a randomized, prospective, double-blind study with a 2×2 factorial design, which means that the volunteering men received either one of the supplements, b2x2-select-vierkantoth supplements or no supplements (but placebo instead), without knowing which treatment they would receive.
The trial volunteers were randomly assigned to one the following treatments:

  1. 200 µg of selenium and 400 IU of vitamin E per day. (both supplements)
  2. 200 µg of selenium per day and placebo
  3. 400 IU of vitamin E per day and placebo
  4. two different placebo’s (neither supplement)
    (µg = micrograms, IU = International Units)

Enrollment for the trial began in 2001 and ended in 2004. Supplements were to be taken for a minimum of 7 years and a maximum of 12 years. Therefore the final results were anticipated in 2013. However, but due to the negative preliminary results, SELECT participants still in the trial are now being told to stop taking the pills. The participants will continue to have their health monitored by study staff for about three more years, continue to respond to the study questionnaires, and will provide a blood sample at their five-year anniversary of joining the trial, to ensure their health and to allow a complete analysis of the study. (see SELECT Q & A).

In an interview with CBS, one of the investigators Dr Katz, said he was highly disappointed and concerned, because he had high hopes for the trial. “I”m disappointed with the study. I’m very concerned about the results of the trial.

more about “Vitamin E A Flop In Prostate Cancer T…“, (with 15 sec advertisement first) posted with vodpod. This video is derived from CBS news.

Dr. Klein, one of the principal investigators, has published as many as 14 publications on the SELECT trial (see PubMed). He has always been a strong advocate of this huge trial.

The question now is:
Was there enough evidence to support such a large trial? Could this result have been foreseen? Would the trial have had different outcomes if other conditions had been chosen?

The SELECT trial seems to add to the ever growing list of disappointing “preventive” vitamin trials. See for instance this blogpost of sandnsurf on “a systematic review of all the published randomized controlled trials (RCTs) on multivitamins and antioxidant supplements in various diseases, and their effect on overall mortality” concluding:

“Taking the antioxidant vitamins A (and its precursor beta-carotene) and E singly or in multivitamins is dangerous and should be avoided by people eating a healthy diet. On a diet like that recommended here, the intake of these and other important vitamins should be high, with no need for supplementation.”

Quite coincidentally I commented to Sandsnurf blogpost referring to the SELECT trial, 1 week before the bad outcome was announced):

Indeed, in many RCT’s vitamin supplements didn’t have the beneficial effects that they were supposed to have. Already in the early nineties, adverse effects of beta-carotene (higher mortality in smokers) have been shown in several RCT’s. Still, because vitamin E had an expected positive effect on prostate cancer in one such trial, vitamin E is now being tested together with selenium (2X2) in a very large prostate cancer trial. Quite disturbingly, 8 times higher doses vitamin E are being used (400IE) compared to the original study. If the Lawson study is right, the outcome might be harmful. Worrying.

It might be argued that it is easy to criticize a study once the outcome is known. However, this critique is not new.

Already in 2002 a very good critique was written by MA Moyad in Urology entitled: Selenium and vitamin E supplements for prostate cancer: evidence or embellishment?

Here I will summarize the most important arguments against this particular trial (largely based on the Moyad paper)

  • SELECT was based on numerous laboratory and observational studies supporting the use of these supplements. As discussed previously such study designs don’t provide the best evidence.
  • The incidence, or rate of occurrence, of prostate cancer was not the primary focus or endpoint of the few randomized controlled trials studies on which the SELECT study was based.
  • A 2×2 design is inadequate for dose-response evaluations, in other words: before you start the trial, you have to be pretty sure about the optimal dose of each supplement and of the interactive effect of vitamin E and selenium in the particular doses used. The interaction between two agents might be synergistic or additive, also with respect to any negative (i.e. pro-oxidant) effect.
  • Eight times higher vitamin E doses (400IE) have been used than in the ATCB study showing a benefit for vitamin E in decreasing prostate cancer risk! This is remarkable, given the fact that high doses of anti-oxidants can be harmful. Indeed, a prospective study has shown, that vitamin E supplements in higher doses (> or =100 IU) are associated with a higher risk of aggressive or fatal prostate cancer in nonsmokers.
  • Other forms of vitamin E and selenium have been proposed to be more effective. For instance dietary vitamin E (gamma tocopherol and/or gamma tocotrienols) might be more effective in lowering prostate cancer risk than the chemically-derived vitamin E (dl-alpha tocopherol acetate) used in SELECT. Also the used selenomethionine might be less effective than organically-bound selenium.
  • Selenium and vitamin E supplements seem to provide a benefit only for those individuals who have lower baseline plasma levels of selenium or vitamin E.
  • There may be other compounds that may be more effective, like finasteride, lycopene, statins (or with respect to food: a healthy lifestyle)

Katz said. “I would have hoped this would have been the way to prevent cancer in this country.”

Isn’t it a little bit naive to expect such huge effects (25% less prostate cancers) just by taking 2 supplements, given the thoughts summarized above?

In the interview, shown in the CBS-interview LaPook concludes “This is a major disappointment, but it is also progress. Because it’s also important to know what does not prevent cancer.”

Well I wonder whether it is ethical ànd scientifically valid, to do such a costly experiment with 35.000 healthy volunteers, based on such little evidence. Do we have to test each single possibly effective food ingredient as a single intervention?

SOURCES:
Official publications and information

- EA Klein: http://www.ncbi.nlm.nih.gov/pubmed/12756490
- Lippman SM, J Natl Cancer Inst. 2005 Jan 19;97(2):94-102. Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). (PubMed record)
- new2.gif The results of the SELECT trial are published in JAMA: Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial. Scott M. Lippman, Eric A. Klein et al SELECT)JAMA. 2008;0(2008):2008864-13, published online December 9th 2008.

- SELECT Q&A: www.cancer.gov/newscenter/pressreleases/SELECTQandA
- General information on SELECT http://www.crab.org/select/
- Information on Study design (from Cancer Gov.clinical trialsSWOG s0000) and from clinicaltrials.gov

- More information on study designs and the ATCB trial (on which this study was based) in a previous post: the best study design for dummies

NEWS
- CBS Evening News Exclusive: Vitamin E And Selenium Fail To Prevent The Disease In Large Clinical Trial, NEW YORK, Oct. 27, 2008
- Los Angelos Times; Vitamin E, selenium fail to prevent prostate
- Emaxhealth: NCI stops prostate cancer prevention trial. With many good links to further information








Follow

Get every new post delivered to your Inbox.

Join 610 other followers