Future perspective from the President-Elect

Fasten Your Seat Belts for Flying High

First, I am indebted to our Editor, Dr Ajit Sahai, for asking (Inviting!) me to contribute to our Bulletin. He has spiritedly taken up the challenge to raise the level of the ISMS Bulletin by including several write-ups on issues and achievements of the Society. As per his suggestion, I take this opportunity to provide my perspective for future of the Society for consideration of the esteemed members of this august body.

I must thank my colleagues at the outset for proposing that I lead the Society during the two-year period from 1st of January 2015 to 31st of December 2016. I agreed as I was retired and this was a good time for me to payback to the discipline that has given me in life beyond my wildest aspirations – not just in terms of material gains but also in terms of respect internationally.  

This Society has always been dear to me and at the core of my professional activities. I was lucky to be in conversation with Dr RN Srivastava for discussing the need to raise this kind of group before this could take a shape. I was unlucky though to miss its first meeting in 1983, as I was on a Visiting Faculty assignment at the Ohio State at that time. I had the opportunity to work with Dr Srivastava at MLN Medical College, Allahabad, in the years 1969 to 1971, where he was Reader and I was Lecturer at that time. It is entirely due to his encouragement and contribution that we could produce some benchmark biostatistical papers on modeling in filariasis and multifactorial analysis of blood pressure levels that were published in Indian Journal of Medical Research at the beginning of my career in early 70s. I was happy to be a secondary author of these papers but, thanks to his greatness, he insisted that I be the first author for these primarily statistical papers. That set the tone for my research endeavours rest of my life, and explains my emotional connect with the Society he founded.

Having paid my tributes to the Founder-President of ISMS, I must admit that a lot has happened during this expanse of 30 years since then. Extremely knowledgeable stalwarts have been heading this Society and they all have contributed in their unique ways. It is because of their enormous inputs that the Society is what it is today. I salute them. The life-membership of the Society has grown to more than 800. It now confers 10 awards at the time of the annual conference each year. The conference has been organized in every corner of the country. My tributes to the organizers of the conferences who worked incessantly for making it a grand success each year. I look forward to a wider participation in the years to come. The list of theses office bearers and the conference organizers is available at http://isms-ind.org/PastAnnualConf.html. This website is being very ably managed by the Department of Biostatistics of CMC, Vellore. This is the first such department in India and has been inspiration for many of us. Dr Anil Mathew, the General Secretary, has undertaken a massive exercise to update the list of members and their addresses on the website. The Treasurer, Dr Ajay Bansal, has applied for a PAN card for the Society. If granted, that will save nearly Rs 15,000/- annually now being deducted as income tax on the interest earned on the deposits in the bank. This saving can be utilized for more interactive running of the Society.

A large number of medical colleges and Institutes of Medical Sciences are opening in every part of the country and the awareness of importance of biostatistics in medical research and practice is steeply increasing. Pharmaceutical industry may also be hiring as the policy for conducting trials within the country firms up. We must gear up to the groundswell in biostatistics personnel across the country. The Society is set to grow in next few years like never before. This upsurge can be attributed primarily to the MCI regulations that require an equivalent of Lecturer in Biostatistics in each medical college. The Society may have to take more proactive steps than done so far to ensure that a Biostatistics Unit is setup in each medical college and a full department in all medical PG and research institutes. This needs to be expanded to include pharmacy, dentistry and nursing. This was never considered before but has great potential. I intend to peruse this with full vigour. We all can help in generating this thrust by doing what we are expected to do – produce high quality research that demonstrates that biostatistics is beyond analysis, and is essential to discover meaning of a mass of data. Let us rise to the occasion and publish papers and reports with high biostatistics content.

A related issue is qualifications required to fill up positions of biostatisticians in the industry and teaching/research institutions. Although the generic meaning of ‘bio’ includes disciplines such as agriculture and zoology, convention is strengthening to restrict this to health and medicine. To avoid this confusion, I started using the term ‘medical biostatistics’ long ago. This includes pharmacy, dentistry, and nursing, among others. Now that we have Master’s and doctoral courses in health statistics, biostatistics, medical statistics, and biometry, the Society may have to actively pursue so that these graduates get priority over those who have degree in statistics or mathematical statistics. Many may disagree, and that view too needs to be given due consideration. We should go by consensus. An incident was recently brought to our notice where candidates with degree in biostatistics were excluded as the advertisement talked only about Master’s in statistics. This Society can play a very effective role in spreading awareness so that this kind of aberrations does not occur.

The Society has been deliberating for long regarding starting something like an Indian journal of biostatistics. That indeed is a very desirable goal. Beside its financial viability, the feasibility has been questioned time and again because of likely shortage of quality papers. It may not be desirable to publish medical papers with some statistical analysis in this biostatistics journal as there are many medical journals for this purpose. In any case, many medical journals in India are also struggling because of lack of quality papers. My crude definition of a biostatistics paper is that it evidences crucial role of biostatistics methods in its results. For me, the best testimony of this is that the first author is a biostatistician. At least in some research endeavours, the biostatistician must lead. Funding agencies these days are liberal and they are looking for worthwhile projects. Biostatisticians across the country must seize the opportunity and conduct research at their own initiative. For primary data we can have medical colleagues as collaborators, otherwise a large amount of secondary data are available free on internet these days for anybody to indulge. Methodological developments also such as health indexes, scoring systems, nomograms, and mapping are not too difficult.

Any frequency less than quarterly of a journal is detested, and quarterly means at least 24 papers are published each year – 6 in each issue. For this we must have at least 50 submissions. Also, there must be willingness to submit it to an Indian journal that is yet to be indexed. Many of you would realize that this is a tall order. My review of PubMed indexed publications reveal that we are way behind at present in producing biostatistics papers. I hope we raise the bar in India and soon start producing at least 50 papers/articles per year with a biostatistician as the first author. Once that happens, the spectre of publishing an Indian journal of biostatistics would clearly emerge for the Society to take its cognizance. I call upon the members of this Society to do this quickly so that the journal becomes a reality. In the mean time, please send your original thoughts to the Editor of our Bulletin. I am sure the Editor will be happy to give it a sympathetic consideration.

The Society must try to expand and make in-roads to other disciplines. I have already mentioned about pharmacy, dentistry and nursing. Others could be AYUSH systems, physiotherapy and para-medical sciences. Biostatistics is practically non-existent in such disciplines. We need to demonstrate and convince how biostatistics is helpful in these disciplines for improving their scientific content. I will take up this as a challenge in the near future.

The Society has been lucky to receive huge donations recently. I expect that this will increase further in course of time. Some of us, particularly those retired, are capable of making larger donations. I call upon our colleagues to be generous and help in enriching the Society they have built up over the years. This can be viewed as a payback to the discipline. The payback can occur in a variety of other ways also, such as setting up websites of the type http://www.MedicalBiostatisics.com with free biostatistics material. This website has been visited by users from more than 120 countries. I wish a time will come when the Society will set up such a website itself to serve its members in particular and the biostatistics professionals in general. Another form of payback was an offer last year to transfer the publication of the book Basic Methods of Medical Research to the ISMS. The premise was that the Society makes money by selling it to the non-members at the regular price while giving it to the members at the cost price reflecting 50% discount. However, due to the constraints of storage and managing the remittances, the proposal could not be accepted.

To those biostatisticians who doubt their bright future, let me add that human variations and uncertainties are bound to propel this subject to its new high. Opportunities for research, writing books, national and international reports, etc., are making it a proverbial ‘sexiest’ profession.

You can see that a large number of activities are lined up for the next few years that could satiate your appetite. I know that some of you are yearning for flying high. Get set, and fasten your seat belts for a take off at a high trajectory. I promise sincere efforts but whether it remains a fantasy or turns into reality would depend on the cooperation of our esteemed members. I hope all will chip-in and do their bit. Your suggestions for further improvements are welcome.

Abhaya Indrayan
[email protected]
http://indrayan.weebly.com  

Delighted to see a debate published in August 2013 issue of the Int J Epidemiol (IJE) on how representative sample from a defined population helps or scuttles scientific research. I am quoting from an article by Rothman and others:
"Here we suggest that representativeness may be essential for conducting opinion polls, or for public-health applications, but it is not a reasonable aim for a scientific study." 
"Clearly, representativeness does not, in and of itself, deliver valid scientific inference. If a study population is representative of some larger source population, the overall associations observed in the study population may not apply to every subgroup. The overall effect is merely an average effect that has been weighted by the distribution of people across these subgroups. Thus, if you have a sample that is representative of the sex distribution in the source population, the results do not necessarily apply either to males or to females, but only to a hypothetical person of average sex."

"Surveys vs causal studies: One way to distinguish science from the kind of information that surveys produce is its overall applicability in space and time. Scientific statements ideally serve to describe nature in a way that is not limited to one time and one place"

Those subscribing to IJE can log on to see http://ije.oxfordjournals.org/content/42/4/1012.full
for details.

Visit http://www.MedicalBiostatistics.com


APACHE scores

Among many severity scoring systems mentioned in this Section, APACHE scores are the most commonly used and deserve some understanding. The basic premise in these scores is that worst physiological derangement noted during first 24 hours after admission in an intensive care unit (ICU) more or less determines the chance of hospital survival as these define organ insufficiency. This implies, though, that treatment and care are not of much consequence as they are nearly same in hospitals across the United States where this system was evolved. APACHE-I was proposed in the year 1981 and was surprisingly accurate in predicting mortality in patients in a variety of ICUs. An exception noted later was the patients requiring coronary by-pass graft where the physiological derangement was high but mortality was low. APACHE-I considered 34 routinely collected physiological measurements and required no extra efforts. Each of these measurements was assigned weight according to the severity of derangement. For example, if serum pH value is either <7.15 or ≥7.70, the weight is +4 as both are considered equally grave, whereas normal value between 7.33 and 7.49 has weight zero as this is no derangement (Knaus WA, Draper EA, Wagnwer DP, Zimmerman JE. APACHE II: A severity of disease classification system. Crit Care Med 1985; 13:818-829.). Slightly higher pH value between 7.50 and 7.59 was assigned weight +1 but on the lower side the value between 7.25 and 7.32 was assigned weight +2 as this is considered relatively more harmful. Sum of these weights for 34 measurements was APACHE. Higher the score, more is the chance of death. However, this was found too complex for adoption.

APACHE-II is the simplified version of APACHE-I and included only 12 physiological measurements. But it added points for age ranging from 0 for <45 years to 6 for ≥75 years, and previous history (5 points for nonoperative or postoperative emergency patients and 2 points for elective postoperative patients). Maximum possible score is 71 although in practice none exceeds 55. A score of 40 or more has been seen to be strongly associated with hospital death. These scores were woven into a logistic regression (discussed later in the book) with mortality as the outcome using data from a large number of ICUs across the United Sates. The equation derived was

Ln( ) = - 3.517 + (0.146*APACHE-II score) + (0.603, only if postoperative surgery) + (diagnostic category weight) ,

where R is the predicted risk of death, and diagnostic category weight was separately derived for 50 disease groups. For example, this weight for asthma/allergies is –2.108 and for cardiogenic shock is +0.393. Negative weight implies that the risk of mortality is less and positive weight implies that the risk is more. These weights are available in Knaus et al. (1985).

Subsequently, APACHE-III appeared between 1991 and 2002 in several different versions. This included 17 physiological variables, adjustment of location and length of stay before ICU admission, and used splines for statistical modeling. The last version of APACHE-III covered 96 disease groups. APACHE-IV appeared in 2006 and included 116 disease groups. This revised the prediction equation, used five new predictors, extended splines, and made prior length of stay continuous in terms of minutes and not just in integer days. The details of APACHE-IV have been described by JE Zimmerman and AA Kramer (Outcome prediction in critical care: the Acute Physiology and Chronic Health Evaluation models. Curr Opin Crit Care 2008; 14:491-497).

In short, APACHE-III and IV are more complex and only marginally increase the predictive accuracy over APACHE-II. Thus many still prefer APACHE-II. The percentage of ICU patients correctly classified into survive/death by APACHE II was observed as 85.5% in U.S. hospitals and the area under ROC curve was 0.863 (Knaus et al. 1985). Note that correct prediction is not as high as the hype around this scoring system. Moreover, not many studies are available that can guide us regarding use of APACHE in developing countries where ICU care and mortality could be very different.

This scoring system is applicable to critical cases wherein survival is known not to exceed 80%. If I am naïve and use this as predictivity for survival without using any scoring system, I would be right in at least 80% cases. Thus a scoring system such as APACHE-II adds just about 5% to the accuracy of prediction. You may like to examine if it is worth taking and using more than 12 physiological measurements for a gain of paltry 5%.

Notwithstanding the problems just enumerated, APACHE scoring is still useful in many setups. You can legitimately compare severity of cases admitted in intensive care unit (ICU) of one hospital with that in another hospital, or in two or more groups such as severity in people in different occupations. Similarly, if a regimen is effective in 72% cases with APACHE-II score between 20 and 24, and another is effective in 78% with the same score, you are confident of 6% difference in efficacy. Also, if average APACHE-II score in critical cases admitted in a hospital during 2005-2009 is 17 and the average rises to 21 in cases admitted during 2010-2014, it would be legitimate to say that the cases admitted later are more severe. Actual utility of APACHE scores lie in this kind of comparison rather than in predicting survival. 

It is gratifying to note that our model of a Department of Biostatistics and Medical Informatics has now been replicated by such prestigious institution as Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, and Jawahar Lal Nehru Institute of Post Graduate Medical Education and Research (JIPMER), Pondicherry. They have setup new department with similar names. We set up such a department in the University College of Medical Sciences, Delhi, in the year 1995 although it was an independent Division till earlier. It is a full department since the year 2005. Dr A. Indrayan was the first head of this department. This kind of Department was set up in SGPGI in the year 2010 and in JIPMER in the year 2012.

I wish the medical science tells me how I am going to die. As articulated in my Views published in BMJ (http://indrayan.weebly.com/nurture-heart-disease.html), my preferred mode of death is heart attack. The reason--simple. Almost no sustained pain to self and the family.
The medical science should be sufficiently advanced so that a person, during his or her life time, can promote the risk factors of choice for increasing chance to die by the chosen cause of death in old age.
If my premise is accepted, the entire heart care research should be directed to such ailments in young age and not for old age. Young age risk factors should be identified for control and old age risk should be identified for promotion for those who want. Any takers.