A qualitative analysis of iodine prophylaxis predistribution as a viable strategy in nuclear emergency preparedness

Anirudh Chandra; Murali Seshadri Iyengar; Probal Chaudhury

doi:10.4103/rpe.RPE_50_20

REVIEW ARTICLE

Year : 2020 | Volume : 43 | Issue : 3 | Page : 123-133

A qualitative analysis of iodine prophylaxis predistribution as a viable strategy in nuclear emergency preparedness

Anirudh Chandra, Murali Seshadri Iyengar, Probal Chaudhury
Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India

Date of Submission	23-Sep-2020
Date of Decision	15-Oct-2020
Date of Acceptance	16-Oct-2020
Date of Web Publication	6-Jan-2021

Correspondence Address:
Anirudh Chandra
1-201-S, Mod Labs, Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai - 400 085, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/rpe.RPE_50_20

Abstract

Off-site nuclear emergency preparedness and response plans have conventionally focused on sheltering, stable iodine prophylaxis, and evacuation of residents as the primary short-term protective actions. Among these, the effectiveness of administering stable iodine prophylaxis has been affirmed over the years, by its ability to reduce intake of radioiodine and minimize the incidence of thyroid cancer in the administered population. The hypothesis of this study was that an advance distribution of prophylaxis, also called predistribution, to households during the preparedness stage is justified. To validate this hypothesis, we carried out a systematic literature review of existing studies on this topic. We also used multi-attribute utility theory to select relevant literature as per the criteria specific to this study. A detailed qualitative analysis was carried out to find the evidence that either substantiated or disproved our hypothesis. We found that over the years, there has been a steady increase in the number of articles advocating a predistribution strategy, especially following nuclear accidents. The most commonly held views against predistribution were as follows: (i) it would lead to accidental ingestion or possible overdose, (ii) it would be misplaced and not serve its purpose at the time of emergency, and (iii) it would not be cost-effective to implement such a distribution. The most common arguments supporting the hypothesis were as follows: (i) it offered maximum effectiveness as it could be immediately administered upon declaration of emergency, (ii) it reduces risk to the first responders who may otherwise be involved in distribution, and (iii) it serves as a last mode of radiation protection when consumed immediately and all other protective actions fail. This study found overwhelming evidence in support of the hypothesis, and hence, we suggest that a predistribution strategy for prophylactics is justified on the grounds of effective and timely radiation protection.

Keywords: Iodine prophylaxis, iodine thyroid blocking, multi-attribute utility theory, nuclear accident, potassium iodide, predistribution, systematic literature review

How to cite this article:
Chandra A, Iyengar MS, Chaudhury P. A qualitative analysis of iodine prophylaxis predistribution as a viable strategy in nuclear emergency preparedness. Radiat Prot Environ 2020;43:123-33

How to cite this URL:
Chandra A, Iyengar MS, Chaudhury P. A qualitative analysis of iodine prophylaxis predistribution as a viable strategy in nuclear emergency preparedness. Radiat Prot Environ [serial online] 2020 [cited 2023 May 30];43:123-33. Available from: https://www.rpe.org.in/text.asp?2020/43/3/123/306282

Introduction

Nuclear power plants generate tremendous amounts of energy with minimal fuel consumption and have been gradually playing a major role in fulfilling the energy requirements of many countries around the world. Its usefulness is not only confined to the energy sector but also branches out to the medical and industrial sector in the form of cancer treatment, radiography, quality control, etc. Its usefulness does not take away the fact that harnessing such energy is not an easy job and entails certain occupational hazards, such as any other industry or technology. To negate this, several engineering safety measures are in place in every nuclear facility as a part of regulatory requirement. One such requirement is the presence of preparedness and response plans for any likely accident(s) or emergency.

The fact that certain categories of nuclear facilities are liable to release radioactive materials into the public domain in the event of such accidents^[1] had ushered in the requirement for an off-site emergency plan. Off-site nuclear emergency preparedness and response plans have conventionally focused on sheltering, stable iodine prophylaxis, and evacuation of residents as the primary protective actions.^[2] These protective actions, also called countermeasures, are intended to counter different possible exposure pathways through which the general public may get exposed to the radioactive materials released during the accident.

One such protective action of interest is the distribution and administration of stable iodine prophylaxis (also known as iodine thyroid-blocking [ITB] agent), which is primarily meant to counter any exposure due to inhalation or ingestion of isotopes of radioiodine. As far as its inclusion in any off-site emergency preparedness plan goes, it has had a checkered history. Initial skepticism about its possible side effects and usefulness in the early years of the nuclear industry^[3],[4] gave way to regulatory confidence in its efficacy after the occurrence of three major nuclear accidents in history. The response during the nuclear accidents at Three Mile Island (TMI) (1979), Chernobyl (1986), and Fukushima (2011) served to strengthen the requirement of stable iodine prophylaxis in any nuclear emergency preparedness plan.

This study does not intend to question the usefulness of such a protective action. Instead, we intend to question the method of implementing this protective action. Conventionally, stable iodine has been distributed as a prophylactic via a central agency/body only in the event of a nuclear emergency.^[3] However, response during the major nuclear accidents and lessons learned from it paints a different picture. An overwhelming feedback^[5],[6] has been the need for advance distribution of stable iodine to households to ensure its maximum efficacy. This study intends to validate this hypothesis by carrying out a systematic literature review and qualitative analysis.

Background on stable iodine prophylaxis

Impact of radioactive iodine

Large quantities of volatile radioisotopes of iodine (henceforth called radioiodine), which are daughter products of uranium fission, are some of the earliest to escape to the atmosphere in the event of a nuclear accident.^[7] Once released, they internally contaminate the human body, either via inhalation or ingestion of contaminated foodstuff.^[8] After they enter the body, they are no longer metabolically differentiable from stable nonradioactive iodine. As a result, they proceed to get concentrated in the thyroid gland, from the blood plasma, where they function as precursors to thyroid hormones.^[9] According to Zanzonico and Becker, in euthyroid individuals receiving sufficient dietary iodine, the maximum accumulation of radioiodine in the thyroid occurs by 36–48 h. In iodine-deficient individuals, the uptake from the blood to the thyroid is faster, and hence, the maximum accumulation occurs earlier, i.e., by 12–24 h.^[10] Although 70%–90% of the inhaled radioiodine will be discharged from the body through urine,^[11] the problem arises when the remaining accumulated radioiodine starts irradiating the thyroid gland. If the absorbed dose due to the irradiation is sufficiently high, then it may result in late-stage thyroid nodules and/or cancer and may even induce hypothyroidism at higher absorbed doses by destroying the thyroid hormones.^[7],[10]

Need for stable iodine prophylaxis

Two protective actions have the ability to block the two major pathways of radioiodine exposure in the early phase of the accident – (1) sheltering with windows closed and covering the nose and mouth have the ability to prevent inhalation of radioiodine to a certain extent; (2) control and screening of contaminated foodstuff have the ability to prevent the ingestion of radioiodine, but again, only to a certain extent. These protective actions are by no means fool proof and other measures are required that can counter any inhaled or ingested radioiodine.

The uptake of radioiodine into the thyroid can be prevented by oral administration of the medically prescribed amount of stable iodine as a prophylactic. This stable iodine acts as a thyroid-blocking agent, and although several alternatives have been proposed,^{[12],[13],[14]} potassium iodide (KI) remains the popular ITB agent of choice. Whatever be the choice of blocking agent, its effectiveness is largely dependent on the time of administration as well as its dosage.

Clinical studies^{[10],[15],[16]} have shown that this prophylaxis is 99% effective in blocking the thyroid and preventing uptake of radioiodine if implemented at or shortly before exposure. Its effectiveness drops to 50% if implemented 3–4 h after exposure, while it becomes practically useless (7%) if implemented 24 h after exposure. Conversely, an early administration of KI is also not useful. Its effectiveness is negligible (5%) if implemented 96 h before exposure, increases to 75% if implemented 48 h before exposure, and further increases to 93% if implemented 24 h before exposure.^[8]

When it comes to dosage, different pharmacological doses of KI are suggested for different population groups. These recommendations vary slightly from country to country. For example, the US Food and Drug Administration (FDA)^[17] states that individuals aged 18 years and above are recommended 130 mg of KI while the same dosage is recommended for individuals aged 12 years and above by many European countries.^[18] The World Health Organization (WHO) also recommend that individuals above the age of 12 years should be prescribed 130 mg of KI or tablets with 100 mg of equivalent mass of iodine.^[19] However, in India, the administration of 170 mg of potassium iodate is prescribed to individuals above the age of 12 years.^[20] It is also observed that universally, the recommended dosage for children aged between 3 and 12 years is 50% of the adult dosage, while infants are recommended 25% of the adult dosage.

Distribution of stable iodine prophylactics

The WHO suggests that the distribution of prophylaxis in any strategy is always in conjunction with a formal protocol that involves logistics of the prophylaxis and training of the responsible agencies.^[19] Since there is limited time for administering ITB following a nuclear accident, prompt availability of tablets in the vicinity of nuclear reactors is important. To fulfill this need and maintain its effectiveness, the report states that predistribution of tablets to households in the vicinity of nuclear reactors (up to 30 km, which is the outer limit of Urgent Protective Actions Planning Zone recommended by the International Atomic Energy Agency [IAEA]) should be considered and even suggests that citizens may purchase the tablets from their nearest supplier. A centralized distribution is suggested for areas further away from the site with the assumption that there is comparatively more time to administer the tablets at these locations, and sometimes, it may not be feasible to predistribute to the increased number of households at larger distances.^[19]

Besides the WHO, the IAEA also stresses the importance of stable iodine prophylaxis in its latest general safety requirement report, GSR Part 7,^[1] and mandates member states to include this action in their emergency plan. However, the scheme for distributing these prophylactics was not mentioned in this report. An earlier report on actions to take following a severe accident at a light water reactor^[21] in 2013 shed some light on this. In this report, the inherent unpredictable nature of release after core damage was cited as a reason to predistribute stable iodine prophylaxis. In addition, the report cited inhalation as the major pathway of exposure within 2 h of any accidental release and considered such an inhalation of radioactive iodine to result in severe deterministic effects in the thyroid and fetus. To effectively negate the possibility of such effects, the report advocated the predistribution of stable iodine prophylactics to homes and community shelters for their prompt use upon the declaration of a general emergency (also known as off-site emergency).

Methodology

Defining the study hypothesis

This study tries to understand the validity of a given distribution strategy in a manner that ensures reproducibility and authenticity of the findings. To begin with, we give a general definition of two distribution strategies:

Predistribution – In this strategy, the tablets are distributed in the preparedness stage among the households in the emergency planning zone (EPZ) who then consume them as per directives from appropriate authorities upon the declaration of a general emergency; it may also be called as advance distribution
Centralized distribution – In this strategy, the tablets are stocked in the preparedness stage in the primary health centers (hospitals/pharmacies) and community shelters (schools, community halls, etc.,) in the EPZ and distributed among the population upon the declaration of a general emergency.

The two strategies are similar insofar as prior stocking of prophylaxis is concerned. They differ in the nature of distribution and time for consumption – while predistribution allows citizens to immediately self-administer the tablets at their homes when a general emergency is declared, there would be considerable delay in administration if the tablets are centrally distributed to them from a hospital or a community shelter. However, this apparent advantage of predistribution over centralized distribution demands rigorous scrutiny of literature to assert its validity, and we proceed to do so with this hypothesis in the following sections.

Systematic review of literature

This study systematically reviews the assorted literature from different scientific databases and then proceeds to analyze the literature to extract information to substantiate either of the distribution strategy.

Search methods

A cursory survey of available literature showed that studies on this topic are frequently found in the MEDLINE and SCOPUS databases. The MEDLINE database was accessed via the PubMed article search engine, while the SCOPUS database was accessed via the ScienceDirect article search engine. In addition, three other databases were considered for the sake of

completion – JSTOR, IEEE Xplore, and Database of Open Access Journals.

Each search engine has a specific search query system which allows the user to narrow down on a specific article. An initial broad search strategy was adopted to cover as many studies as possible that were even remotely related to the study hypothesis. The search strategy was broken down into four different concepts:

Intervention: This represents the nature of intervention to the nuclear emergency. Search terms – (”iodine,” “iodine thyroid blocking,” “iodine prophylaxis,” “prophylaxis”)
Form of intervention: This refers to the specific form of iodine prophylaxis. Search terms – (”KI,” “potassium iodide,” “stable iodine”)
Location: This covers prophylaxis distribution only in the context of nuclear emergencies. Search terms – (”Fukushima,” “Chernobyl,” “nuclear,” “nuclear accident,” “nuclear emergency”)
Mode of intervention: This is the form of prophylaxis distribution. Search terms – (”distribution,” “administration”).

The specific search queries used for the study are presented in [Table 1]. In addition to parsing these databases, we were also interested in finding technical reports submitted on this topic by different governmental bodies/agencies of countries that have a nuclear power program. However, we found that these reports were not available on the databases mentioned above, so instead, we used the Google Search engine to retrieve freely available reports using the search terms mentioned above along with the respective country's name.

Table 1: Search queries for different databases

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Data collation and analysis

The collected literature was downloaded from the respective databases and collated in a spreadsheet for analysis. The Preferred Reporting Items for Systematic reviews and

Meta-Analysis (PRISMA) flowchart^[22] was used to formalize the process of selection of relevant articles for analysis [Figure 1]. The collated records (articles are referred to as “records” in the PRISMA process) were selected/screened/analyzed by applying three criteria of increasing scrutiny at different levels of the PRISMA process.

Figure 1: PRISMA flowchart for systematic review

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Screening criteria

The initial collated records were screened on the basis of the following criteria:

The records must be written in English language
The records must be one of the following types of article - review article, research article/journal article, case study, guideline, editorial/opinion/commentary
The records must be relevant to the study, after checking their title and abstract.

Eligibility criteria

The screened records were then checked to see if they were eligible for detailed qualitative analysis for testing the study hypothesis. In this study, we have considered a multi-criteria decision-making (MCDM) approach^[23] (Mardani et al., 2015) to select the relevant records. A multi-attribute utility theory^[23] was designed to assess the records on the basis of the following attributes/criteria:

Distribution scheme – The record gave information on the strategy of prophylaxis distribution
Distribution logistics – The record gave information on the quantity/cost/expiry of the prophylaxis distributed
Distribution target – The record gave information on the population groups to be distributed prophylaxis.

Each of these attributes was given an equal weightage, while the type of record was given differential weights [Table 2]. Each screened record was reviewed and graded on a 5-point Likert scale [Table 3]. A weighted sum of the attributes and record type yielded the utility value for each record. Records with a utility value >3 were considered eligible for detailed qualitative analysis.

Table 2: Criterion weights

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Table 3: 5-point Likert scale for grading records

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Detailed qualitative analysis

The eligible records were individually studied to extract data and information on various aspects of prophylaxis distribution – historical evidence, insights, prophylaxis stockpiling, shelf-life of stocks, quantities supplied, consumers of the prophylaxis, etc. This analysis is presented in the “Discussion” section.

Results

A total of 30 records (articles) were found eligible for qualitative analysis from a list of 1732 records (as on June 24, 2020), with most of the records being indexed in PubMed database [Figure 2]. This is likely because the subject of iodine prophylaxis is more common in the field of public health and medicine and PubMed is a prominent database for articles in this field. Most of the screened records, i.e., 37%, were technical reports issued by different countries and 33% were review articles [Figure 3] that included systematic reviews, comprehensive reviews, and review of historical nuclear accidents. Case studies came in the third place, at 27%, and these highlighted the findings of distribution strategies carried out in the vicinity of nuclear power plants.

Figure 2: (a) Number of records collated per database. (b) Number of eligible records per database

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Figure 3: Pie chart of type of eligible article/record

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Most of the eligible records (barring technical reports) were published in journals that covered public health and medicine aspects (45%) followed by journals on health physics and radiation protection (20%). This was because very few of the articles exclusively studied the distribution strategies of prophylactics. They largely covered the physiological aspects of prophylactics, with a section or paragraph dedicated to discussing its distribution. As a result, it is more likely that they would be published in journals on medicine and public health.

Most of the eligible records (barring technical reports) were from the USA followed by Japan [Figure 4]. This was expected because each these countries suffered nuclear accidents. We expected a large number of articles from the European Union, given that Chernobyl occurred in Russia, but we did not find evidence for the same. From Figure 4, we can see that there is a distinct increase in the number of articles (on distribution aspects of prophylactics) with each decade after the 1970s. The number of articles on prophylactic distribution in the USA has been persistent since 1979 after the TMI nuclear accident (1979). After the Chernobyl accident in 1986, more articles were published from the USA, the UK, and some countries in Europe, especially since the effectiveness of prophylaxis was demonstrated in Poland immediately after the accident at Chernobyl and results of follow-up studies in 1990s. Japan started contributed to this body of work after the Fukushima nuclear accident in 2011, after experiencing firsthand the logistic nightmare of prophylactic distribution when evacuation takes place.

Figure 4: Chronology of the country-wise eligible records. The vertical lines represent the three major nuclear accidents in history (Three Mile Island - 1979, Chernobyl - 1986 and Fukushima - 2011)

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Discussion

Detailed analysis of the eligible articles revealed that there were three overarching themes in these articles that suited our study objectives – historical evidence for distribution, actual distribution, and logistics of distribution strategies and arguments for and against distribution. We proceed to distill this evidence in the following sections.

Historical evidence for prophylactic distribution

The first major nuclear accident in history was the TMI nuclear accident on March 28, 1979, at Dauhpin County, Pennsylvania, USA. It was a partial leak in Reactor No. 2 of the TMI Nuclear Generating Station which resulted in low releases of radioactivity to the environment. Prominent among the released radioactivity was ¹³¹I which resulted in low levels of exposure and no demonstrable health effects among the surrounding population.^[24] This accident was described in four articles in this study,^[5,24-26] and each gave a differing account of the amount of ¹³¹I released, with values ranging from 13^[5] to <32 Ci.^[24] Insights on prophylactic distribution and logistics during this accident were observed in Leung et al., 2017 and Adalja, 2011. Forty-eight hours after the accident, pregnant women and children within 8 km were advised to evacuate and eventually 200,000 people within 24 km of the plant chose to evacuate. Despite these large numbers, KI was neither available on site nor for the population in the vicinity of the power plant.^[5] In an effort to ameliorate the situation, the US FDA dispatched 250,000 bottles of KI, which was termed as a “crash effort.” Unfortunately, since its use was not indicated in any emergency response plan at the time, it was not administered to any individual.^[25]

Seven years later, on April 26, 1986, the Chernobyl nuclear accident occurred which was devastating in its consequences. The accident occurred at the Reactor No. 4 of the Chernobyl Nuclear Power Plant, near the town of Pripyat in Ukraine. This accident resulted in widespread dispersion of large amount of radioactivity and subsequent development of approximately 5000 cases of thyroid cancer in children and young adults due to exposure to the released ¹³¹I.^[25] Five articles in this study discuss the prophylactic response to the Chernobyl accident,^{[5],[8],[24],[26],[27]} and once again, there are differing accounts on the amount of ¹³¹I released in this accident, with values ranging from ~7^[27] to ~140 MCi.^[24] It seemed that, although there was a policy for KI administration in the USSR at the time, its timely distribution could not be carried out because of poor communication and general secrecy surrounding the accident.^[26] However, conflicting studies cited in Ginzburg and Reiss state that the Soviet government was able to supply iodine prophylaxis to the children in Pripyat within 12 h of the accident as a result of which 97% of them received doses <0.3 Gy.^[27] This article also cross-references another source in saying that the Soviet government was able to administer prophylaxis to nearly 5,400,000 people including 1,690,000 children within the 1^st year of the accident.^[27] The population surrounding the Chernobyl nuclear power plant was largely iodine deficient and had greater propensity to absorb the released ¹³¹I,^[25] yet timely prophylactic response was not available for them. However, it was observed that the prophylactic response of Poland to the Chernobyl accident was more effective than Ukraine, and in fact, Poland was the only country in the surrounding region to do so.^[5] Within 3 days of learning of the radioactive releases from the accident, the Polish government ordered their national pharmacies to prepare KI tablets. Within hours of production, the KI was bottled and distributed, and within a day, 75% of the Polish children had received this KI. Cumulatively, 10.5 million single doses were provided to children and 7 million doses to adults.^[8],[2],[5]

The most recent nuclear accident at Fukushima, Japan, occurred on March 11, 2011, 25 years after the Chernobyl accident. This accident occurred at Reactor No. 1, 2, 3, and 4 of the Fukushima Daiichi Nuclear Power Plant (FDNPP) in Okuma, Fukushima Prefecture, in Japan. Seven articles in this study describe in detail the prophylactic response of the Japanese government.^{[5],[6],[8],[24],[25],[27],[28]} In the nuclear meltdown that occurred, the amount of ¹³¹I released differed among the articles with values ranging from 3.2^[5] to 14 MCi.^[28] From the lessons learned at Chernobyl and TMI, the Japanese government had a directive in place for stockpiling KI tablets within 10 miles or the EPZ of nuclear facilities.^[6] These were, however, to be distributed to the residents only after the general emergency was declared at the nuclear facility. After the Japanese government declared a general emergency at FDNPP, the first protective action initiated was evacuation of nearby residents. This was accompanied by a sheltering-in-place order. The first to take any initiative in distributing iodine prophylaxis was Tomioka town, where within 24 h of the accident 21,000 tablets were distributed. They were soon followed by Futaba and Namie towns who, additionally, ordered the intake of the distributed tablets. Naraha and Okuma towns distributed only after 3 days, while Iwaki town distributed after 4 days and each ordered the intake of the distributed prophylactics.^[29] Hatanaka et al. found that there was disparity between prophylactics being distributed and orders being issued for their intake,^[29] both at the level of the prefecture and at the level of the national government. One of the early orders issued by the national government was to issue KI to evacuees under 40 years of age, but this was not properly communicated.^[5] A possible reason for this poor communication and distribution could be the fact that multiple sequential evacuations were carried out which may have hampered the responding authorities. The Japanese government, on the basis of projected doses and their national thyroid exposure threshold of 100 mSv, distributed KI tablets to children in the contamination area but not to the general public. Studies of these children later revealed that they had never received the thyroid doses necessary for KI administration.^[8] Despite no clear directions from authorities on KI usage beyond the emergency protection zone, people outside these zones still self-administered KI out of fear and precaution.^[24]

Understanding the evolution of prophylactic distribution

Based on this historical evidence, this study identifies three distinct phases of prophylactics distribution.

Phase I, called the skepticism phase, was when countries were directed by their respective nuclear regulatory authorities to include stable iodine prophylaxis in their emergency response and preparedness plan, but lack of historical empirical data provoked a mixed reaction toward this directive. This phase was characterized by conflicts between those who advocated prophylaxis on radiation protection grounds, citing a few experimental evidence, and those who do not deem it justified to invest in large stockpiles of prophylactics, due to lack of evidence of adverse reactions of radioiodine exposure in the public domain.^[30],[31] This phase was also characterized by a growing discourse on the side effects of KI prophylaxis. The nuclear accident at TMI prompted authorities in the US to emphasize the need for KI to be included in all nuclear emergency preparedness plans, but there was no emphasis on the means for its distribution.^[26] The only evidence for any kind of distribution strategy was in the form of a case study conducted at Tennessee on predistribution of stable iodine tablets.^[32]

Phase II, called the justification phase, began after the Chernobyl nuclear accident. The accident opened the eyes of nuclear regulatory authorities all over the world on the usefulness of stable iodine prophylaxis. The extent of release of ¹³¹I, the subsequent incidence of thyroid cancers in the inhabitants, and the timely response of Poland gave a massive impetus to regulatory authorities and national bodies to include stable iodine prophylaxis in their emergency response plan. This phase is also characterized by the rise in the number of articles and the reports on distribution strategies for KI. Many of these studies^{[33],[34],[35],[36],[37],[38]} discussed the impact of distributing KI tablets in the preparedness stage versus distributing it during the emergency. Most of these studies were feasibility studies, and they relied on surveys and interviews of the residents living in the vicinity of nuclear power plants.

Phase III, called the optimization phase, began when many countries started adopting a strategy of predistributing prophylaxis, particularly in Europe.^[18],[39] However, it was the response of the Japanese government to the Fukushima nuclear accident that highlighted the importance of advance distribution of prophylactics.^{[24],[25],[40],[41],[42],43]} Here was a nation who had adopted the KI distribution in their preparedness program but failed to implement it in a timely and effective manner.^[6],[29] This brought about a need to optimize the existing distribution strategy to a predistribution strategy.^{[5],[6],[8],[44],[45]} However, there are still proponents for and against this particular distribution strategy, and we will try and summarize the crucial points of these arguments in Section “Viability of a predistribution strategy.”

Prophylaxis logistics and distribution strategies

The main logistics of concern for stable iodine prophylactics distribution are the quantity to be supplied and the shelf-life of the supplied prophylaxis. KI in the tablet form has a shelf-life of 5–7 years with capsulation enhancing this shelf life. Braverman et al. in their review have cross-referenced studies on the improvement of tablet shelf-lives and shown that KI in the granular form exhibits the highest extension in shelf-life, 20 years past their expiration date.^[8] They even go on to suggest the use of KI in the encapsulated granules instead of the tablet form. Humidity also plays a role in reducing the efficacy of these prophylactics by reducing the active iodine content in them, and it would be prudent to store them in dry, watertight storage.^[8] The quantity to be supplied would depend on the size of the target population, number of target households, and number of other facilities (such as pharmacies, schools, and community centers).^[31]

Any sort of distribution strategy for prophylactics must take into account the following considerations:^[32]

Availability of existing KI stocks
Target population size
Number of households in the vicinity
Number of possible community shelters and offices
Topography of the region
Existing evacuation plans
Availability of first responders
Public acceptance
Meteorological conditions.

Once the above factors are considered, then any one of the following distribution strategies for stable iodine prophylaxis may be adopted:

Strategy 1 - Predistribution to homes

Here, the prophylactics are distributed directly to households and residents carry out self-administration upon receiving directives from appropriate authorities after general emergency is declared.^{[18],[19],[32],[33],[35],[37],[44]} Some popular methods of predistribution involve sending the required dosage by post^{[18],[33],[35]} or door-to-door distribution.^[32] These generally involve filling out a questionnaire which covers any pre-exiting medical conditions before applying for KI tablets. Residents are encouraged to consult their local physicians before applying for the KI tablets.

Strategy 2 - Predistribution from central stockpiles

Here, the residents are asked to collect the prophylactics from a central storage/stockpile,^{[8],[18],[19],[34],[36],[37],[44],[46]} typically their local pharmacy, and asked by appropriate authorities to self-administer after general emergency is declared. One popular method is for residents to apply for KI tablets after which they would receive coupons which could be exchanged for KI tablets at their local pharmacies.^[18],[36] Another popular method involves holding meeting with local residents which serve to not only sensitize them on the effectiveness of the prophylaxis but also distribute the tablets.^{[6],[18],[34]}

Strategy 3 - Distribution from central stockpiles

This distribution takes place via local pharmacies or other central stockpiles after general emergency has been declared.^{[19],[20],[24],[28],[29],[38],[47]} The prophylactics are distributed to each household in the vicinity of the reactor by emergency first responders who also give instructions on administration. The distribution would also take place at community shelters where evacuees would be brought.

Viability of a predistribution strategy

The detailed qualitative analysis revealed that an over-whelming majority of countries and agencies advocate a predistribution strategy for prophylactics. However, a conclusion can be drawn on its viability only after weighing the pros and cons of such a strategy. From our analysis, we provide the following benefits and costs, which are graphically summarized in [Figure 5].

Figure 5: Summary of the pros and cons of predistribution strategy (a) Pros (benefits) of a pre-distribution strategy (b) Cons (costs) of a pre-distribution strategy

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Benefits of a predistribution strategy

Maximize effectiveness: The maximum effectiveness of KI is within a few hours of radioactive iodine exposure, which would be ensured by a predistribution strategy^{[5],[6],[26],[32],[35],[36],[42]}
Last means of protection: If evacuation or sheltering in place or control on contaminated food is not possible or delayed in the locality, then predistributed KI tablets would afford a degree of protection against exposure to radioiodine^[5],[6],[33]
Protection of infants: Infants in the population may not be able to avoid intake of contaminated milk, possibly due to the failure to interdict contaminated food products^[5]
Public demand: Even if there are no official recommendations for KI administration, demand for KI will still be high following a nuclear emergency^{[5],[25],[41]} and this strategy can fulfill that
Counter-fight or flight: Some population may be in fight or flight mode and may choose to evacuate even if not ordered to do so. In such cases, a message of “take KI and shelter in place” may ameliorate this situation^[5]
Hampering evacuation: Distributing KI on the day of the emergency would hamper any evacuation plan^[5],[34]
Counter unintentional evacuation: Unintentionally, evacuation to locations with higher levels of radiation exposure may be negated by the intake of predistributed KI tablets^[5]
Reduce risk to first responders: Risk of first responders being contaminated is high in centralized distribution strategies, and hence, a predistribution strategy would reduce this risk of exposure^{[33],[36],[37]}
Reduce risk to residents: Predistribution to households reduces the risk of exposure to the general public if they have to go to the distribution point to collect the KI tablets when general emergency is declared^{[33],[36],[37]}
Divert first responders: Centrally distributing KI tablets after declaration of general emergency would divert first responders from other crucial and time-sensitive activities such as evacuation.^[30]

Costs of a predistribution strategy

Not cost-effective: It is not cost-effective to predistribute to individual households and have a follow-up plan to replenish expired stock, especially with a changing population^[26]
Affect public psychology: Have a negative impact on public psychology regarding the nuclear power plant in their vicinity^[26]
Accidental ingestion: Distribution to households would create problems of accidental ingestion/overdose/no knowledge when to use^{[26],[30],[34],[37],[38],[43]}
Failure to re-stock: Failure to replace iodine past expiration date^[30],[37]
False sense of security: KI may give a false sense of security and reluctance to follow official advice to evacuate^[5],[25]
Food control more effective: Control of food (milk) pathway would reduce exposure to radioiodine and hence does not justify predistribution of KI^[5]
Low perception on exposure: The risks of exposure to radioactive iodine isotopes, particularly from inhalation, are “perceived” to be low and hence do not warrant predistribution^[5]
Forget or misplace stocks: Even if KI is predistributed, many people may not have timely access to it or forget where the KI was stored.^{[5],[35],[38],[43]}

From this analysis, we can see [Figure 5] that the major reason for implementing a predistribution strategy is to maximize the effectiveness of the prophylaxis due to the uncertainty surrounding releases during nuclear emergency, while the major argument against this strategy is accidental intake of the supplied tablets, leading to possible overdose or some sort of side effect, despite there are no conclusive studies that categorically state the harmfulness of KI prophylaxis.

Conclusions

The effectiveness of administering stable iodine prophylaxis has been affirmed over the years, by its ability to reduce the incidence of thyroid cancer in the administered population. Although it is unfortunate that such an affirmation has arrived at the tail of disasters, it is a strong reason for including KI prophylaxis in any nuclear emergency preparedness plan. The current study does not aim to question this well-established dogma of the prophylaxis, but instead it makes an attempt to justify its early distribution and administration. The hypothesis under question was whether an advance distribution of prophylaxis, also called predistribution, to households during the preparedness stage is justified or not. To validate this hypothesis, we carried out a systematic literature review of existing literature on this topic. We also employed the use of MCDM method to weed out irrelevant literature and select suitable articles to analyze. This study is fundamentally an aggregation and distillation of available literature to find the most relevant reasons for and against predistribution of stable iodine prophylaxis by chronologically and qualitatively assessing this literature.

Our findings show that, with every nuclear disaster, there is a renewed interest in prophylaxis distribution and the current lot of studies focus on predistribution as compared to earlier studies that questioned the very need for a distribution plan. We have found that many of the countries pursuing a nuclear power program have adopted a predistribution strategy for prophylaxis, with a few countries still preferring the strategy of centralized distribution after declaration of emergency. The overwhelming reasons for not preferring a predistribution strategy were the inadvertent intake of prophylaxis by residents and misplacement of supplied prophylaxis, thereby negating its effectiveness at the time of emergency. On the other hand, the major reason cited for predistribution was that it ensured maximum effectiveness of the prophylaxis at the time of the emergency and did not hamper the implementation of other protective measures. In this study, the number of articles favoring predistribution over any form of centralized distribution was higher for the former than the latter. Combining this finding with the fact that there are no conclusive studies on the negative health effects of KI prophylaxis, we believe that the predistribution of stable iodine prophylaxis is a more effective strategy. Its effectiveness at the time of the emergency will convincingly justify the cost in supplying KI to households and in maintaining a regular program to replenish this supplied stock. However, it is for the nuclear regulatory body of the nation to determine the justification of such a strategy, and this study provides a means to that end. Consensus among the various stakeholders of such a strategy is the only way forward in its adoption in the national nuclear emergency preparedness and response plan.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	International Atomic Energy Agency. Preparedness and Response for a Nuclear or Radiological Emergency. GSR Part 7. Vienna: International Atomic Energy Agency; 2015.
2.	International Atomic Energy Agency. Arrangements for Preparedness for a Nuclear or Radiological Emergency. Safety Guide No. GS-G-2.1. Vienna: International Atomic Energy Agency; 2007.
3.	Shleien B, Halperin JA, Bilstad JM, Botstein P, Dutra EV Jr. Recommendations on the use of potassium iodide as a thyroid-blocking agent in radiation accidents: An FDA update. Bull N Y Acad Med 1983;59:1009-19.
4.	Yalow RS. Risks in mass distribution of potassium iodide. Bull N Y Acad Med 1983;59:1020-7.
5.	Leung A, Bauer A, Benvenga S, Brenner A, Hennessey J, Hurley J, et al. American Thyroid Association (ATA) Scientific Statement on the Use of Potassium Iodide (KI) Ingestion in a Nuclear Emergency. Thyroid 2017;27:865-77.
6.	Ojino M, Yoshida S, Nagata T, Ishii M, Akashi M. First successful pre-distribution of stable iodine tablets under Japan's New Policy after the Fukushima Daiichi Nuclear Accident. Disaster Med Public Health 2017;11:365-9.
7.	Pfinder M, Dreger S, Christianson L, Lhachimi SK, Zeeb H. The effects of iodine blocking on thyroid cancer, hypothyroidism and benign thyroid nodules following nuclear accidents: A systematic review. J Radiol Prot 2016;36:R112-30.
8.	Braverman ER, Blum K, Loeffke B, Baker R, Kreuk F, Yang SP, et al. Managing terrorism or accidental nuclear errors, preparing for iodine-131 emergencies: A comprehensive review. Int J Environ Res Public Health 2014;11:4158-200.
9.	Hänscheid H, Reiners C, Goulko G, Luster M, Schneider-Ludorff M, Buck AK, et al. Facing the nuclear threat: Thyroid blocking revisited. J Clin Endocrinol Metab 2011;96:3511-6.
10.	Zanzonico P, Becker D. Effects of Time of administration of dietary iodine levels on potassium iodide (KI) blockade of thyroid irradiation by I¹³¹ from radioactive fallout. Health Phys 2000;78:660-7.
11.	Yoshida S, Ojino M, Ozaki T, Hatanaka T, Nomura K, Ishii M, et al. Guidelines for iodine prophylaxis as a protective measure: Information for physicians. Japan Med Assoc J 2014;57:113-23.
12.	Pahuja DN, Rajan MG, Borkar AV, Samuel AM. Potassium iodate and its comparison to potassium iodide as a blocker of ¹³¹I uptake by the thyroid in rats. Health Phys 1993;65:545-9.
13.	Pahuja DN, Jagtap VS, Sonawane VR, Rajan MG, Samuel AM. Calcium iodate Another effective blocker of radioiodine uptake by the thyroid gland. Health Phys 2005;89:92-4.
14.	Harris CA, Fisher JW, Rollor EA 3^rd, Ferguson DC, Blount BC, Valentin-Blasini L, et al. Evaluation of potassium iodide (KI) and ammonium perchlorate (NH₄ClO₄) to ameliorate ¹³¹I-exposure in the rat. J Toxicol Environ Health A 2009;72:897-902.
15.	Phan G, Rebière F, Suhard D, Legrand A, Carpentier F, Sontag T, et al. Optimal KI prophylactic dose determination for thyroid radiation protection after a single administration in adult rats. Dose Response 2017;15:1-8.
16.	Verger P, Aurengo A, Geoffroy B, Le Guen B. Iodine kinetics and effectiveness of stable iodine prophylaxis after intake of radioactive iodine: A review. Thyroid 2001;11:353-60.
17.	US EPA. PAG Manual: Protective Action Guides and Planning Guidance for Radiological Incidents. Washington, DC: United States Environmental Protection Agency; 2017.
18.	Jourdain J, Herviou K, Betrand R, Celemente M, Petry A. Medical Effectiveness of Iodine Prophylaxis in a Nuclear Reactor Emergency Situation and Overview of European National Practices. Fountenay-aux-Roses: RISKAUDIT IRSN/GRS International; 2010.
19.	World Health Organization. Guidelines for Use in Planning for and Responding to Radiological and Nuclear Emergencies. Geneva: World Health Organization; 2017.
20.	Atomic Energy Regulatory Board. Criteria for Planning, Preparedness and Response Nuclear or Radiological Emergency. Mumbai: Atomic Energy Regulatory Board; 2014.
21.	International Atomic Energy Agency. Actions to Protect the Public in an Emergency due to Severe Conditions at a Light Water Reactor. Vienna: International Atomic Energy Agency; 2013.
22.	Moher D, Liberati A, Tetzlaff A, Altman G; The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA statement. PLoS Med 2009;6:1-6.
23.	Mardani A, Jusoh A, Nor K, Khalifah Z, Zakwan N, Valipour A. Multiple criteria decision-making techniques and their applications – A review of the literature from 2000 to 2014. Econ Res-Ekonomska Istraživanja 2015;28:516-71.
24.	Dauer LT, Zanzonico P, Tuttle RM, Quinn DM, Strauss HW. The Japanese tsunami and resulting nuclear emergency at the Fukushima Daiichi power facility: Technical, radiologic, and response perspectives. J Nucl Med 2011;52:1423-32.
25.	Adalja A. Medicine for policymakers. Biosecur Bioterror 2011;9:405-7.
26.	Becker D, Zanzonico P. Potassium iodide for thyroid blockade in a reactor accident: Administrative policies that govern its use. Thyroid 1997;7:193-7.
27.	Ginzburg HM, Reis E. Consequences of the nuclear power plant accident at Chernobyl. Public Health Rep 1991;106:32-40.
28.	Nishikawa Y, Kohno A, Takahashi Y, Suzuki C, Kinoshita H, Nakayama T, et al. Stable iodine distribution among children after the 2011 Fukushima nuclear disaster in Japan: An observational study. J Clin Endocrinol Metabol 2019;104:1658-66.
29.	Hatanaka T, Yoshida S, Ojino M, Ishii M. The communication of information such as evacuation orders at the time of a nuclear power station accident -recommendations for responses by the national government and electric power utilities to the “information disaster”. Japan Med Assoc J 2014;57:293-319.
30.	Resolution concerning the stockpiling of potassium iodide in New York City in the event of a nuclear accident. The Committee on Public Health, The New York Academy of Medicine. Bull N Y Acad Med 1981;57:395-9.
31.	Becker D. Reactor accidents: public health strategies and their medical implications. J Am Med Assoc 1987;258:649-54.
32.	Fowinkle E, Sell S, Wolle R. Predistribution of potassium iodide – The Tennessee experience. Public Health Rep 1983;98:123-6.
33.	Astbury J, Horsley S, Gent N. Evaluation of a scheme for the pre- distribution of stable iodine (potassium iodate) to the civilian population residing within the immediate countermeasures zone of a nuclear submarine construction facility. J Public Health Med 1999;21:412-4.
34.	Blando J, Robertson C, Pearl K, Dixon C, Valcin M, Bresnitz E. Assessment of potassium iodide (KI) distribution program among communities within the emergency planning zones (EPZ) of two nuclear power plants. Health Phys 2007;92:S18-26.
35.	Carney J, DeFlorio F, Erickson N, McCandless R. Enhancing nuclear emergency preparedness: Vermont's distribution program for potassium iodide. J Public Health Manage Practice 2003;9:361-7.
36.	Le Guen B, Hemidy P, Garcier Y. French approach for the distribution of iodine tablets in the vicinity of nuclear power plants. Health Phys 2002;83:293-300.
37.	Millership S. Distribution of stable iodine in a nuclear emergency Are we prepared? J Public Health Med 1998;20:191-5.
38.	Moss S. Feasibility Study for Potassium Iodide (KI) Distribution in New York City. New York: Brookhaven National Laboratory; 2005.
39.	Perko T, Turcanu C, Schroder J, Carle B. Risk Perception of the Belgian Population: Results of the Public Opinion Survey in 2009. Mol: SCK-CEN; 2010.
40.	Nuclear Energy Agency. International Short-Term Countermeasures Survey: 2012 Update. Paris: Nuclear Energy Agency; 2013.
41.	Whitcomb R, Ansari A, Buzzell J, McCurely M, Miller C, Smith J, et al. A public health perspective on the US response to the Fukushima Nuclear Emergency. Health Phys 2015;108:357-63.
42.	Spallek L, Krille L, Reiners C, Schneider R, Yamashita S, Zeeb H. Adverse effects of Thyroid blocking: A systematic review. Radiat Protect Dosim 2012;150:267-77.
43.	Zwolinski L, Stanbury M, Manente S. Nuclear power plant emergency preparedness: Results from an evaluation of Michigan's potassium iodide distribution program. Disaster Med Public Health Prepared 2012;6:263-9.
44.	Canadian Nuclear Safety Commission. Emergency Management and Fire Protection: Nuclear Emergency Preparedness and Response. Ontario: Canadian Nuclear Safety Commission; 2016.
45.	Public Health England. Public Health Protection in Radiation Emergencies. London: Public Health England; 2019.
46.	Kok-Palma Y, Leenders M, Meulenbelt J. Dutch distribution zones of stable iodine tablets based on atmospheric dispersion modelling of accidental releases from nuclear power plants. Radiat Prot Dosimetry 2010;140:234-41.
47.	Strahlenschutzkommission. Use of Iodine Tablets for Thyroid Blocking in the Event of a Nuclear Emergency with Release of Radioactive Iodine: Recommendations by the German Commission on Radiological Protection. Bonn: Strahlenschutzkommission; 2018.